Bringing research to lifeAnnual Report 2010-2011

The MonTreal neurological insTiTuTe of Mcgill universiTyCentre of exCellenCe in CommerCialization and researCh

To obtain additional copies of this report or for more information, please contact:

External Affairs: Montreal Neurological Institute and Hospital 3801 University Street Montréal, Québec H3A 2B4

Tel.: 514 398-1902 Fax: 514 398-8072

Communications.mni@mcgill.ca www.mni.mcgill.ca

Le rapport est disponible en français.

1 MESSAgE FroM THE ProvoST, McgILL UNIvErSITy

3 MESSAgE FroM THE INTErIM DIrECTor, MoNTrEAL NEUroLogICAL INSTITUTE

4 THE NEUro

5 gLoBAL STrATEgy For THE CENTrE oF ExCELLENCE IN CoMMErCIALIzATIoN AND rESEArCH AwArD

6 MNI CECr CorPorATE PLAN 2010-2011

7 THIrD yEAr rESULTS AND oUTCoMES

7 CoMPArATIvE rESULTS AND oUTCoMES

9 FUNDED ProjECTS 2010-2011

19 PUBLIC oUTrEACH AND ENgAgEMENT ACTIvITIES

21 CoMMErCIALIzATIoN AND BUSINESS DEvELoPMENT

•industrypartners

•patentapplications

•revenuesgeneratedfromcommercialactivitiesin2010-2011

•revenuesgeneratedfromcoreservicesin2010-2011

22 MNI CorPorATE PLAN 2011-2012

23 FINANCIAL STATEMENTS

25 CECr INITIATIvES AND FUNDINg

27 govErNANCE

•cecradvisoryBoard

•cecrprogramandinternalrevieWcommittee

•cecrcommercialiZationcommittee

28 CECr INvESTIgATorS, STUDENTS AND PoSTDoCTorAL FELLowS

editors: natasha laliberté, sandra McPherson, PhDcontributors: natasha laliberté, sandra McPherson, PhD, victor swoboda

The Montreal neurological institute is proud to be a Killam institution, one of five canadian institutions supported by the Killam Trusts. in 1966, the izaak Walton Killam Memorial endowment fund and fund for advanced studies were established at the Mni through the bequest of Dorothy Johnston Killam. These funds support the academic and training mission of the Mni, and play a crucial role in advancing our work in neuroscience.

The production of this report was made possible by the support of the Montreal neurological institute centre of excellence in commercialization and research award from the government of canada.

contents

We would like to thank the faculty and staff of the Mni for contributing their time in presenting their research reports and results.We would also like to acknowledge the work of photographer owen egan.

Design and production: c

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is buttressed by the reputation and impact of scholars like those at the Mni. indeed, the Montreal neurological institute helps to propel Mcgill thanks to its global standing by engaging in new and exciting curiosity-driven basic research at the bench, which, thanks to its strong working relationship with the Montreal neurological hospital (Mnh), can help transform patient care by providing an environment for the rapid translation of scientific discovery into life-saving techniques and therapies.

This unique partnership between basic, curiosity-driven research and discoveries and a commitment to bring new ideas quickly to the practice of medicine is enhanced, enriched, and guaranteed because of the co-existence of the Montreal neurological institute of Mcgill university and the Montreal neurological hospital of the Mcgill university health centre. The combination of the Mni and the Mnh is often referred to as “The neuro”.

The success of the Mni’s cecr projects are a testament to the shared vision and the determination of the talented scientists that work at The neuro, and we look forward to building on this success as we begin the search for new leadership.

as Provost, the chief academic officer after the Principal, of Mcgill university, i take great pride in the Mni as a centre of excellence. let me outline a few of the highlights contained in this year’s annual report. Mni scientists working on the cecr have:

¬ applied for 8 patents over the last three years

¬ published 35 papers during the course of the cecr

¬ submitted 12 new papers to peer reviewed journals in 2010-2011

¬ trained a new cohort of scientists

¬ formed new commercial and business partnerships

¬ leveraged the cecr award 1.4-fold in terms of grants, revenues and gifts-in-kind.

This tremendous progress in innovation reflects, in my opinion, rather precisely the goals and objectives of the cecr program. The Mni cecr continues to allow the dedicated faculty and research teams at The neuro to make significant inroads in our understanding and effective treatment of neurological disorders.

let me close by thanking the government of canada for showing such faith in the Montreal neurological institute of Mcgill university by the 2007 award recognizing it as a centre of excellence in research and commercialization. i trust that this report will allow you to consider the recognition of the Mni to have been truly in the national interest of canada.

With best regards,

Prof. Anthony C. Masi Provost, Mcgill university

When the Montreal neurological institute of Mcgill university was recognized by the government of canada as a “centre of excellence in commercialization and research”, a requirement of the funding agreement (article viii) was that i, as Provost of the university, present an annual report on activities, demonstrating how the terms and conditions of the award are being met. This year, it is with both pride and sadness that i write to fulfill that obligation.

it is a sad duty, indeed, to report that Dr. David colman, who so ably served as a professor of neuroscience at Mcgill university and as the Director of the Montreal neurological institute ( Mni ), passed away suddenly, unexpectedly, and prematurely on June 1, 2011, leaving a wonderful legacy of nearly a decade of leadership that among many other things includes the 2007 recognition by the government of canada that the Montreal neurological institute of Mcgill university deserved to be a centre of excellence in commercialization and research ( cecr ). Dr. colman made a difference and he will be missed.

at the same time, i am very proud of the accomplishments of the Mni, its investigators, students, and staff, and the wonderful contributions that they have made. This annual report details the progress that has been achieved by researchers at the Mni thanks to the significant financial contribution and framework for innovation that the cecr award has provided.

Mcgill is one of canada’s premier research-intensive universities, and the Mni is one of Mcgill’s best examples of our commitment to advance the frontiers of knowledge, educate the next generation of researchers, and make significant and lasting contributions to society. neuroscience in general is a dominant research paradigm at Mcgill, and the Mni is the true cornerstone of those endeavors. The recognition of Mcgill as one of the world’s leading publicly funded universities

message from the provost Mcgill university

3 4

A Global ChallengeDiseases of the nervous system are the largest and fastest growing area of unmet medical need. Presently, the lifetime risk that you or i will acquire a neurological condition is greater than 1 in 3 and this will rise with anticipated demographic changes. While advances in laboratory and clinical medicine have led to improved outcomes in many neurological disorders, treatment options generally remain limited and therefore these conditions extract a severe cost on patients, families and our health care system. as of 2007, 19% of acute care patient days in canadian hospitals resulted from neurological disease. The economic toll for canada is huge, with recent estimates placing the cost at $8.8B per annum. Thus, it is imperative that new treatment options be identified and put into medical practice.

a unique institution

A teaching and research institute dedicated to innovations in neuroscience

from its inception in 1934, the Montreal neurological institute and hospital — The neuro, has been at the forefront of research into the causes and the treatment of neurological disease. it is one of the largest neuroscience institutes in the world, recognized for the seamless integration of neuroscience research and clinical neurology. neurological institutes under construction in Tianjin china and Brown university are directly modelled on the neuro.

one of the earliest innovations from The neuro, an approach for epilepsy surgery known worldwide as “The Montreal Procedure” is used to this day. clinicians at The neuro see the most difficult neurological and neurosurgical cases. We have 40 clinical trials for various diseases underway. our scientists have been a leading force in developing brain-imaging technologies, the first magnetic resonance imaging (Mri) and positron emission tomography (PeT) scanners in canada were at the neuro, and the scientific community uses The neuro stereotaxic space as a reference for human and primate brain scans. neuro scientists are known worldwide for their pioneering research with approximately 1000 high impact papers published in international, peer-reviewed scientific journals in the last five years alone. Thus, The neuro is a resource for all of canada.

The neuro’s goal is to provide an environment that allows neuroscientists and clinicians to identify the cellular basis of neurological disease and to translate these findings to innovations in clinical practice. We strongly believe that these innovations are best driven by the researchers and clinicians who are experts in their respective areas. The Mni’s status as a premier neuroscience institute and care facility attracts leading investigators, accomplished clinicians and promising students. We maintain key collaborations with neuroscientists not only across the mcGill network, but also with scientists in other universities and centres across Quebec and Canada, and around the world.

The numerous awards received by our investigators and clinicians, our outstanding success rate in obtaining

grants and the wealth of publications in leading scientific journals attest to our standing as a world-class institute with an extremely strong international reputation.

Applying research to understanding and treating neurological diseases

as a teaching and research institute of Mcgill university, the Mni is the centerpiece of Mcgill’s strategic plan in research and training in the neurosciences. 50 faculty members lead international research teams that generate research and translational support from grants, awards and contracts of approximately $22 million per year. our multidisciplinary teams generate fundamental information that spans the full spectrum of neuroscience from cell and molecular biology to brain imaging and cognitive neuroscience. over 300 graduate students and postdoctoral fellows from around the world pursue their studies and scientific training at the Mni each year.

A centre for state-of-the-art treatment of neurological diseases

The Mni’s clinical partner, the Montreal neurological hospital, is one of five hospitals in the Mcgill university health centre (Muhc). The hospital has 85 beds, five surgical suites, state-of-the-art equipment for interventional neuro-radiology, advanced cT, PeT, Meg and Mri scanners, ten specialty day clinics and other facilities. neurologists, neurosurgeons and other specialists hold academic appointments at Mcgill university and train the next generation of physicians.

the neuro“we had an idea for a new approach to antibody production that we developed because we knew it could help our research. The CECr provided the perfect opportunity to take the technology to a broader audience, and recognize a commercial benefit.”

Peter McPhersonThe MNI Antibody resource for Neuroscience research

This report summarizes the activities supported during the third year of the cecr award to The neuro. since The neuro’s founding 77 years ago, the staff at our combined research institute and hospital have worked with intensity and passion to produce fundamental discoveries in the neurosciences and apply them to the treatment of neurological disease and injury. The cecr award has greatly accelerated our ability to move our initiatives forward and is already yielding benefits for the people of canada.

louis Pasteur, one of the great innovators of the 19th century is credited with saying that “luck favors the prepared mind”. at The neuro we work hard to prepare ourselves for those lucky moments.

We bring together the finest minds in the field of neuroscience with state-of-the-art equipment and foster a culture that recognizes that the most important discoveries are often unanticipated. We have to take risks in our research if we are going to make the conceptual leaps that will make a difference and we have to be prepared and opportunistic if we are to take advantage of them. These concepts reflect the strategic vision of Dr. David colman, the Director of The neuro who tragically passed away in June 2011 and they remain firmly embedded in our actions.

The cecr at The neuro has provided the means to take our innovations further and has yielded dramatic results.

Philip A. Barker, PhD interim Director Montreal neurological institute

message from the interim director Montreal neurological institute

5 6

The objectives that were part of the long-term strategy originally defined in 2008-2009 were maintained throughout the 2010-2011 funding period. Over the course of the third year of the MNI CECR we continued to ensure the effective use of the CECR Award and pursued activities that were initiated in 2008 and 2009. In addition, we identified and funded five (5) new projects with apparent commercial potential.

The application and review process that was established in 2008-2009 was maintained, and progress against initial goals and milestones continued to be a key requirement for renewed funding.

For Year 3 of the MNI CECR, we asked MNI clinicians and researchers to apply for funding through the same on-line application process as in Years 1 and 2. In addition to new projects, some of these appli-cations were renewal requests.

Our Program and Internal Review Committee had recommended that our final year’s funding be focused on those projects that showed clear commercialization potential or could lead to rapid translational advances and be sustainable beyond our CECR funding period. The criteria used for our project review was modified to reflect this strategy.

Portions of the Award were also set aside for development of highly qualified personnel, expansion of our public outreach and engagement activities, advancement of commercialization potential and opportunities that presented throughout the course of the year.

Mni cecr corporate plan 2010 -2011

PlAnneD exPenDitures for 2010-2011 were DefineD As follows:

investigator initiated Programs

Biological basis of neurological disease, early stage commercialization $ 565,000

neuroengineering $ 355,000

Translational neuroscience $ 800,000

applied neuroscience and rapid commercialization $ 887,000

clinical trials support $ 370,000

Public outreach and engagement

fellowship Program $ 200,000

Mcgill integrated neuroscience Program $ 60,000

Media relations and outreach $ 255,000

intellectual property protection and business development $ 300,000

opportunity fund $ 300,000

administration $ 100,000

total $4,192,000

Please see page 25-26 for funding allocations per category and project.

“The CECr support of the Experimental Therapeutics Program (ETP) has provided important bridge-funding allowing the establishment of a high quality biological sample repository and enabling the ETP to meet milestones in several areas, including hiring key personnel with expertise in translational research and biomarker development, the enhance-ment of the bio-repository that houses a precious and growing resource of samples and the establishment of several equipment platforms that serve as core facilities for the broader MNI and external communities.”

Amit Bar-orExperimental Therapeutics Program

the mni’s strategy for use of the CeCr award focuses on two major endeavours: developing innovative approaches to research that will lead to effective applications to health care and creating opportunities for commercialization of diagnostic or treatment measures. the mni is pursuing its strategy through five general objectives.

objective 1

accelerate new research in the areas of:

a) biological basis of neurological diseaseb) neuroengineeringc) translational neuroscienced) applied neuroscience

and commercialization

objective 2

enhance clinical trials programs to support work in translational neuroscience

This objective focuses on the development of three programs: the experimental Therapeutics Program; an investigator-initiated clinical trials program; and web-based translational tools designed to bring research results and best practices to physicians and other health care providers. The Mni is also establishing an international network for the Mcconnell Brain imaging centre. These measures aim to facilitate access to academic and clinical resources, data and expertise for researchers and trainees.

objective 3

engage domestic and international students and young researchers in our programs

The Mni will increase opportunities for students, fellows and young researchers to be deployed to various research teams funded by the cecr award.

objective 4

facilitate intellectual property protection, commercialization of research results, and business development of mni inventions

This objective will be achieved through the Mni’s initiative in applied neuroscience and commercialization. a panel of business, financial and scientific consultants who have extensive experience in biotechnology and pharmaceutical industries will oversee commercialization activities.

objective 5

expand public outreach and engagement activities

The Mni will allocate funding to support:

• an International Student and Fellowship Program;

• an annual MNI conference series designed to bring top tier international scientists to Montreal to present their latest work in areas of clinical importance and emerging research technologies;

• the development of web resources and new media for communicating our research and results to the lay public.

global strategy for the centre of excellence in commercialization and research award

“CECr funding to the Pediatric Biomarker project has supported a collaborative initiative to answer key questions related to the mechanisms and targets of disease imitation in multiple sclerosis (MS), the most common cause of progressive neurological disability in young adults in the western hemisphere. This project highlights the Neuro’s unique potential to bridge basic science and clinical research with outcomes that have significant consequences to both our understanding, and treatment of, human disease.”

Amit Bar-or Identification of Novel Initiating Targets and Prognostic Markers of MS in Pediatric-onset Disease

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third year results and outcomes

comparative results and outcomes

in the third year of the CeCr award:

• The MNI attained the objectives that it set out in its 2010-2011 corporate Plan.

• The MNI allocated just over $3.2 million in funding to 29 research activities in the biological basis of neurological disease area, neuroengineering, applied neuro-science and commercialization, translational neuroscience, and clinical trials.

• The MNI received $150,000 in donations towards the purchase of equipment and $7,000 to support the acquisition of data for one of the Mni cecr funded projects.

• The MNI received in-kind donations of approximately $3.3 million in the form of creative talent and advertising (radio, print and television) and in-kind donations from astral Media, st. Joseph communications, Bos and other media outlets and agencies for neuroscience awareness over the past 3 years.

More than 100 published research papers resulted from research conducted on equipment at either the Mcconnell Brain imaging centre or the Microscopy centre.

Mni principal investigators, as part of their CeCr-funded activities:

in the area of attracting top research talent:

• Engaged 39 Baccalaureat, Master’s and Doctoral students and 21 Postdoctoral fellows from across north america and around the globe including Mexico, france, england, ireland, italy, iran, Brazil, Korea, spain, Japan, saudi arabia, Turkey, india, switzerland and china.

• Employed 52 research assistants and technicians and other qualified personnel.

in regards to commercialization of research and access to world-class resources:

• Generated revenues of $130,192 from commercial activities.

• Generated revenues of $ 3,212,345 from core services. More than 200 users accessed these services in 2010-2011.

in pursuit of new collaborations with industry:

• Initiated industry collaborations and licensing agreements with five (5) companies in the pharmaceutical and biotechnology fields.

• Initiated one (1) new clinical collaboration.

in pursuit of internationally competitive research:

• Published 17 papers and submitted 12.

• Successfully applied for close to $2.6 million in funding from outside agencies.

in pursuit of the commercialization of leading-edge technologies:

• Filed one (1) new patent application and moved an existing application to the international phase.

enhAnCeD ProDuCtivity AnD CoMPetitiveness

research-related benefits 2008-09 2009-10 2010-11

Baccalaureat, Master’s and Doctoral students 15 52 39

Postdoctoral fellows 9 24 21

research assistants, technicians and other personnel 43 49 51

funding from outside agencies not applicable $5,000,000 $2,600,000

Donations for purchase of equipment nil $1,300,000 $ 150,000

in-kind donations for neuroscience awareness nil $2,400,000 $ 900,000

research papers published 2 16 17

research papers submitted nil 8 12

Commercialization-related benefits 2008-09 2009-10 2010-11

new clinical collaborations not applicable 2 1

Pharmaceutical and biotechnology industry collaborations and licensing agreements 3 7 5

new patent applications 4 3 1

revenue from commercial activities $ 60,000 $ 155,460 $ 130,192

revenue from core services $2,893,210 $3,345,980 $3,212,345

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funded projects

2010-2011

Most of the applications received in year 3 of the CECr Award were requests for funding renewals. In addition, there were some new project applications that targeted areas with high potential for rapid commercial or translational innovations.

Applications were reviewed by our CECr Program and Internal review Committee. As per their recommendation, our final year’s funding was focused on those projects that had clear commercialization potential or would lead to rapid translational advances and be sustainable beyond our CECr funding period. other criteria considered included: Does the project meet the goals of the CECr? Does the project meet the goals and strategy established by the MNI? For previously funded applications, progress towards initial goals and milestones, as provided in the quarterly updates, was a key requirement for continued funding.

43 applications were reviewed and funding recommendations were forwarded to our CECr Advisory Board for approval: 25 applications received renewed funding and five (5) new applications were funded. In total, 76% of our CECr budget for 2010-2011 was devoted to these 30 research projects.

In the pages that follow, we detail the work that the MNI CECr Award funded in 2010-2011.

research reportsBIoLogICAL BASIS oF NEUroLogICAL DISEASEnew techniques in molecular and cell biology have greatly enhanced neurological disease research. it is now abundantly clear that most neurological disorders result from disruption in the fundamental function of brain cells and their interconnectivity. therefore, to understand normal nerve cell function and to reveal how it is disrupted in models of disease, we must examine neurons at all levels; from the dynamics of sub-cellular organelles to the connectivity of cognitive networks.

Edward FonBiology of Parkinson’s Disease

The discovery of genes responsible for Parkinson’s Disease launched an intense amount of research. however, studies to identify the genes are rapidly outpacing the cell biological work needed to reveal how these genes are part of the disease process. This project examines known proteins implicated in Parkinson’s Disease to determine how they influence survival of neurons.

Michael PetridesAtlas of the Human Cerebral Cortex

The “Mni stereotaxic space” is a “generic” brain stereotaxic space created in 1994 and now used worldwide to specify the x, y and z coordinates of specific brain functions. But to identify the brain areas actually at those coordinates, investigators currently use assumptions modeled on a single brain. This Mni project is scanning normal human brain, analyzing them and incorporating the data into an updated 3D “Mni space”, resolving one of the most pressing problems in functional neuroimaging.

Philip BarkerJoint Protein Production Facility

new therapies for neurological disease are heavily dependent on recombinant proteins that are pure and free of endotoxins. generating these pure proteins in large quantities for in vivo testing is technically difficult and requires expensive infrastructure, so the Mni has partnered with the Biotechnology research institute (Bri) of the national research council (nrc). The cecr funding has provided for a joint Mni-Bri research assistant to supervise production of proteins at the Bri-nrc and to cover operating costs.

Thomas StrohMicroscopy Core Services

almost all fields of neurobiology require sophisticated microscopes and techniques to study the interactions of cells and cellular components of the brain. since 2006, at least 80 high profile publications by Mni researchers contain data acquired in the Mni’s Microscopy centre. cecr funding has been allocated to keep this centre at the cutting-edge, and funds specialized software and hardware, service contracts and technical management.

Eric ShoubridgeResource for the Generation of Induced Pleuripotent Stem Cells

The stem cell field has been revolutionized by the finding that human skin cells, and probably many other cell types, can be induced to a pleuripotent (near-embryonic) state, from which they can be re-trained to become different cells altogether. While there is still much work to be done to fully characterize cells and perfect techniques, this means investigators can induce cells derived from patients with neurological diseases to become whatever cell type is required for modeling the mechanism of disease. stem cells have been generated at the Mni and the work is currently focused on differentiating them. The goal is to develop protocols permitting any investigator to “grow your own neurons”.

Barry BedellPlatform for Integrated, Advanced Animal Research for Complex, Human Neurological, Oncological and Inflammatory Diseases

This resource is an outgrowth of Dr. Bedell’s small animal imaging lab (sail) and creates an integrated technology platform that brings together multi-modality imaging, experimental neuropathology, and molecular studies. This novel platform integration will both increase and accelerate the commercialization opportunities for investigators by giving them a wider range of validation and investigative procedures. it will also help develop, over time, a pool of young talent specialized in these techniques which will make a sound contribution to the advancement of medical research in the community.

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putting genetic brakes on

brain tumoursten years of research have led neurosurgeon Kevin Petrecca to a major breakthrough that has the potential to control aggressive brain cancers called gliomas. examples of gliomas are astrocytoma, oligodendroglioma, oligoastrocytoma and glioblastoma. each year, about two thousand Canadians and sixteen thousand americans develop high-grade gliomas. their prognosis is characteris-tically bleak---most patients do not survive beyond 18 months after diagnosis.

Dr. Petrecca has discovered that a protein called Drr acts to spread cance rous glial cells. This protein is not seen in normal glial cells, but it becomes prominent when glial cells become cancerous. Dr. Petrecca is working in collaboration with Dr. Masad Dahma, James Mcgill Professor in Mcgill university’s Department of chemistry, and together they have developed and jointly patented two gene-based therapeutics that stop the action of this protein.

one technique uses small fragments of Dna that bind to mrna, the molecule that carries a protein’s blueprint. as a result of this binding, cellular mechanisms split the mrna, causing it to stop producing Drr in cancerous cells. With the help of Mcgill university’s office of sponsored research, this technique has been licensed to the american pharmaceutical company, labopharm.

The second technique uses short inhibitory rna sequences. after scanning the entire sequence of the cancer-generating protein molecule, Dr. Petrecca found the most effective inhibitory rna sequences. By eliminating the expression of Drr, he found that he could decrease cell movement in the context of brain cancer.

Past attempts to administer gene-based therapeutics to cancer molecules have failed because the genes break down quickly. Dr. Dahma has a patent for modifying the backbone of these genes in such a way that they become long lasting. This means that the drugs could be administered every few weeks rather than daily – a more effective, easier treatment. negotiations are underway to license the second technique.

“it won’t be long before we put these techniques into action,” said Dr. Petrecca. “The mode of therapeutic delivery is not new. What’s new is the drug. With

labopharm, we could move into Phase one clinical trials to determine drug toxicity within 18 months. The clinical research unit at the Montreal neurological institute is well set up to conduct these kinds of trials.”

Dr. Petrecca acknowledges that these therapies are not a cure for brain cancer, but they do promise to keep the cancers confined and not spread throughout the brain. The biggest problem facing brain cancer patients after surgery is the spread of cancerous cells that remain after surgery.

“We are typically able to remove the original cancerous mass, but it spreads,” said Dr. Petrecca. “if we can keep it where it was on the day that the patient is diagnosed, then we’ll have a major benefit.”

funded projects 2010-2011

Project: a new therapy for high-grade brain cancers

application to health care: could drastically reduce the number of brain cancer deaths

investigator: Kevin Petrecca

Commercialization potential: very high

research reports

summaryresearcher/neurosurgeon Dr. Kevin

Petrecca, Dr. Phuong uyen le and

Mcgill colleagues have developed

novel genetic-based techniques to

control the spread of aggressive

brain cancers.

NEUroENgINEErINgneuroengineering is a new revolution of science and technology that involves using nanoengineering and biomedical engineering tools to answer neurobiological questions – understand, repair, replace, enhance, or otherwise exploit the properties of neural systems.

eliane KobayashiApplication of MEG in the Assessment of the Epileptic Focus

surgery is the only treatment option for patients with drug- resistant focal epilepsy. however, localization of the seizure focus is not always possible, particularly in patients with normal imaging and eeg. Magnetoencephalography (Meg) is a neurophysiological tool that can provide important complementary information to the standard eeg investigation. Meg can identify the location and extent of the focus in a significant proportion of patients with negative eeg, especially neocortical epilepsies. scanning is currently done off-site, however, we expect The neuro’s newly installed Meg scanner to be operational within the next six months. This will allow this project to study patients with focal epilepsies and to determine the role of Meg information in the surgical decision-making process.

andrea BernasconiAutomated Lesion Detection in Drug Resistant Epilepsy

Dr. Bernasconi is developing an on-line commercial service to allow epilepsy centres throughout the world to deposit their Mri data into a central repository at the Montreal neurological institute. Data will be processed off-line in a secure server, and the processed results will be made commercially available to users through protected internet passwords and user-friendly software. The cross-platform software (Windows, linux and MacosX) will be updated regularly. The data repository would be an invaluable clinical tool. Three interdependent modules, for example, will detect dysplasia features, and automatically detect and delineate tiny lesions that would otherwise remain unseen. collaborations are in the works with leading epilepsy centres (cnrs in Paris, Queen square, london, new york university, yale university, university of Melbourne) with other centres expected to join the repository at a rate of ten a year.

outlookPhase One clinical trials to assess toxicity from gene-based anti-DRR therapy are expected within 18 months. Within a year after that, phase two tests could be completed. Negotia-tions are ongoing to license the technique involving RNA sequences. Dr. Petrecca is looking to continue screening for other cancerous molecular pathways.

progressThe genetic-based therapy has been patented. Initial tests over the past year show that the molecule effectively stops glial cancer invasion. Labopharma has licensed the technique.

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getting ahead of alzheimer’s

disease as north americans live longer and the proportion of the elderly continues to rise, the incidence of dementia among the aged, particularly alzheimer’s disease, will increase. diagnosing alzheimer’s disease is still an inexact science, and detecting pre-clinical alzheimer’s disease is impossible. so far, the only sure way to confirm the diagnosis is through a post-mortem examination of a patient’s brain. But dr. louis Collins, a biomedical engineer, and his colleagues have developed a technique using magnetic resonance imaging data that not only determines alzheimer’s disease in living patients in its early phase with a high degree of accuracy, but can predict how quickly the disease will progress.

Work on this technique came out of a thesis on epilepsy by one of Dr. collins’ doctoral students, simon Duchesne. funded by a $100,000 cihr PoP grant, the two developed a technique to characterize the morphology and intensity of Mri data of epilepsy patients. They examined the shape of the brain of epilepsy patients and the intensity of their Mri images to determine the extent of the differences with normal brains. Their studies were able to predict with 80 per cent accuracy those patients who would benefit from epilepsy surgery.

Dr. collins recently received a cihr grant to further develop the technique in relation to alzheimer’s disease. it has a signature mode of atrophy that is different from those of other dementias.

“We can see the effects of atrophy and gliosis,” explained Dr. collins. “atrophy will change the shape of the brain by decreasing the volume of the brain tissue and increasing the size of the ventricular and csf spaces. gliosis can potentially change the intensity of an Mri image. By doing statistical analysis across the entire brain or---if we want to restrict our research---the medial temporal lobe, we can see certain regions whose changes are consistent with people who’ll stay stable with mild cognitive impairment or who’ll get worse and progress to alzheimer’s disease.”

“By looking at these patterns and correlating them statistically with the current status of a diagnostic test, we can see whether the particular pattern corresponds to patients who will stay stable or get worse.”

Dr. collins derived his statistics from both publicly available data bases and from data bases compiled with the collaboration of researchers throughout the world. his statistics cover some two thousand patients.

Dr. collins’ method has several distinct advantages. it is a non-invasive technique, unlike the conventional test for alzheimer’s disease, which detects beta-amyloid and tau protein in spinal fluid. furthermore, the method can be employed at the same time as the Mri scans that patients with memory complaints are normally required to undergo. The cost of using the technique will be determined by the company that licenses it.

The cecr award is enabling additional validation that will facilitate eventual commercialization of this method which could lead to major savings for alzheimer’s disease pharmaceutical trials. in a clinical trial of patients suffering from mild cognitive impairment, only 10 to 15 per cent will develop alzheimer’s disease. This means that a large number of patients need to be involved in a trial to achieve an accurate statistical study. Dr. collins’ method could be used to enrich trial populations to reduce the number of patients needed in a clinical trial by a factor as high as ten. This method can also be applied to individual subjects to improve patient management.

Project: To exploit Mri data in determining the degree of alzheimer’s disease in living patients

application to health care: Makes available an inexpensive tool to assist in the diagnosis of alzheimer’s disease, and to predict the speed of its progression at early pre-clinical stages with high accuracy

investigator: louis collins

Commercialization potential: high

research reports

summaryDr. louis collins has developed a

non-invasive test to diagnose alzheimer’s

disease and to predict the consequent

progression of cognitive impairment.

The test can also differentiate aD from

other forms of dementia.

TrANSLATIoNAL NEUroSCIENCEtranslational neuroscience applies insights gained through fundamental research on brain structure and function to develop novel pharmacological, surgical, and behavioral therapies for neurological diseases and disorders.

William feindelCost-Effective Analysis of the Montreal Procedure for Surgical Cure of Temporal Lobe Epilepsy

opportunities to accurately measure the economic benefits of treatment are rare. The Mni has such an opportunity by having access to patients operated on between 1953 and 1988 by William feindel, an associate of Wilder Penfield and a former neuro director. The surgical operation known as the “Montreal Procedure” developed by Penfield and his team in the 1950’s for temporary-lobe epilepsy is in use at over 100 neurosurgical centers around the world. This study is analyzing the benefits of having arrested the seizures by looking at the employment profile and earning capacity before and after surgery, as well as reduction in the costs of medication and government sponsored social welfare. Preliminary research has shown that lifetime economic benefits can be as high as one million dollars per operated patient.

alain dagher, amir shmuelEarly Diagnosis of Alzheimer’s and Parkinson’s diseases

in canada, alzheimer’s disease alone afflicts one in 20 people over 65 at an annual cost of treatment of $5.5 billion.international efforts to arrest the social and economic costs of dementia have led to the identification of drugs that may slow down the progression of this disease. This in turn drives renewed need for early diagnosis. The team is developing a suite of multi-modal tests – Mri, fMri and eeg – aimed at providing biomarkers for early detection of alzheimer’s and Parkinson’s diseases. The results are encouraging: in the model relating to alzheimer’s, the data differentiates patients with mild cognitive impairment, an intermediary stage; in the Parkinson’s model, the research differentiates subjects with dopamine depletion, related to Parkinson’s, from control subjects.

Bruce PikeImaging Innovation and Translation

The Mni’s Mcconnell Brain imaging centre (Bic) is one of the world’s largest and most productive research-dedicated neuroimaging centres. some 60+ faculty and another 200+ associates use the Bic’s infrastructure and expertise in their clinical and basic neuroscience studies. This includes human Mri scanners at 1.5T and at 3T (for which there are over 100 active research protocols), a 7T small animal Mri, two human PeT scanners, a microPeT small animal system, a cyclotron and radiochemistry lab, a super-computing facility and a Meg scanner. not surprisingly, the Bic is the most costly cog in the Mni mechanism. The centre runs on a cost-recovery model with an annual budget of approximately $4 million, aided by cecr funding of specific core costs. These funds have enabled at least 16 important accomplishments in the past year, including new patents and commercial contracts that have contributed significantly to the ongoing success of the Bic.

amir shmuelClinical Applications of Non-Invasive Manipulation of Neuronal Excitability

Transcranial Magnetic stimulation (TMs) offers an important, non-invasive means of manipulating functional activity to address neurological disorders and investigate the relationship between brain and behaviour. The promise of TMs, however, has been constrained by an incomplete understanding of how it works. a multi-faceted Mni team is documenting the biophysical principles of TMs and identifying exciting new potential therapies in the process. repeated application of TMs – rTMs – has been shown to alter cortical excitability beyond the period of stimulation. a pilot study of ambylopia, a common developmental visual disorder, indicates long-lasting improvements in vision can be achieved through application of rTMs to the visual cortex.

outlookValidation of the technique is virtually complete. It remains for the research software to be adapted for clinical trials to get government approval of the technique. Discussions are underway with companies interested in licensing the technique.

progressTwo patents related to the initial technology have been granted. Two other patents are pending. The technology is developed to a point where in 19 out of 20 MRI scans, it can predict the onset of Alzheim-er’s disease within two years with 80 percent accuracy.

funded projects 2010-2011

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keepingmemories

intactthe old saying – build a better mouse-trap and people will come knocking at your door – would apply to the project undertaken by neuropsychologist Viviane sziklas and her colleague, marilyn Jones-Gotman. they are developing a better test to examine memory function in patients with temporal lobe epilepsy.

for the past several decades, the standard testing procedure in preparation for resection of epileptogenic tissue has been the intracarotid anesthetic Procedure, the current gold standard for estimating memory function in each cerebral hemi-sphere. But the test has drawbacks. it involves catheterization and anesthesia, invasive processes that are nerve-racking for the patient and carry potentially serious risk. This 3-day procedure requires a large, expensive staff that includes a neuro-psychologist, anesthetist, radiologist, eeg technician, and nursing staff. These factors, along with a lack of availability of the drug in many parts of the world, have driven the need for an alternative solution.

Dr. sziklas and Dr. Jones-gotman set a goal of improving the test. They have created a protocol that is non-invasive, more easily administered, more cost- efficient, and takes less than half the time. a single technician can run the test, and the data is interpreted by a neuropsychologist.

“We developed a functional magnetic resonance protocol that we hope will replace the invasive procedure but yield the same data and more,” said Dr. sziklas.

The fMri procedure is based on a pair of highly predictive matched verbal and

nonverbal memory tests, developed in their clinic, that have reliably distinguished patients with left or right temporal lobe epilepsy for over 20 years. They are consistently in demand by epilepsy centres on an international level yet Dr. sziklas and Dr. Jones-gotman have never formally marketed them.

“When people are encoding or recognizing these stimuli, different parts of the brain are particularly involved,” said Dr. sziklas. “over time, we’ve honed the tests to the point where we know which stimuli are most sensitive and have adapted them into an fMri protocol. We also learned how to administer them to get at the different stages of memory that we’re interested in understanding. our fMri method is more precise in terms of specifying which region of the brain is of interest to the surgeon and there’s no need for a catheter or for any anesthetic.”

Dr. sziklas and Dr. Jones-gotman have created a normal brain activation profile by accumulating fMri data of healthy subjects on their behavioural task. Their next step is to develop typical profiles of left- and

right-temporal lobe epilepsy patients. Many patients will need to be scanned, an undertaking that The neuro can easily handle.

The two researchers are also developing a second version of the test. This test could be administered if there is a long delay before a patient’s initial operation, or if a patient requires a second operation.

“We need a second test to ensure that we’re testing memory function in a valid way and that the results are not affected by practice effects from the first test.”

The elegance of the fMri test would make it attractive to the growing number of epilepsy centres around the world, particularly in europe, where many centres lack either the drugs needed for the intracarotid anesthetic Procedure or the staff trained to administer the test.

“These centres would be interested to have this protocol rather than making their own,” observed Dr. sziklas. “We intend to create a procedural manual to be included with the fMri software, to make it very user friendly for other centres.”

Project: a cost-effective fMri solution to replace invasive examina-tion of medial temporal lobe function

application to health care: To provide a tool to enable sparing of essential tissue during surgical planning for intractable temporal lobe epilepsy

investigator: viviane sziklas, Marilyn Jones-gotman

Commercialization potential: Medium

research reportsTrANSLATIoNAL NEUroSCIENCE

denise KleinPre-Surgical Functional Brain Mapping Unit

approximately 200 patients a year at the Mni undergo brain surgery in close proximity to areas critical to vision, movement, sensation or language. To improve pre-surgical mapping, Denise Klein, a cognitive neuroscientist, has brought together experts from the brain imaging group, neuroradiology and neurosurgery to create an integrated, pre-surgical functional brain mapping unit. With cecr funding, this unit has become well established and is scanning roughly two patients per week using new protocols developed by the team with functional magnetic resonance imaging (fMri) and positron emission tomography (PeT). The director of neuro-navigation is working on the integration of the data with neuro-navigation systems for precise, image-guided neurosurgery.

marilyn Jones-Gotman,lesley fellows, alain PtitoThe MNI Cognitive Neuroscience Testing Resource

Tests of a patient’s cognitive abilities are an important component of diagnosis and treatment of epilepsy, head injury and other neurological disorders. By virtue of its work, the Mni has amassed a wide range of proven tests and, due to limitations in currently available commercial tests, the Mni batteries are much sought after. commercialization, however, requires a satisfactory set of normative data. This project will establish data on 300 healthy individuals stratified by age, sex and language as norms for use with patients with epilepsy or head injury, and on a cohort of patients with multiple sclerosis or hiv for use with patients with diffuse brain injury. it will result in the Mni marketing three batteries of specialized tests for different neurological conditions. To maximize user friendliness, most of the tests are being computerized and, to date, data have been collected from 145 patient test sessions and 20 sessions with healthy subjects.

Bruce PikeMR Venography for Image Guided Neurosurgery

Pre-operative three-dimensional scans of the brain’s vasculature are an essential part of a surgeon’s preparation. But an easier, less expensive method is needed to replace the conventional Magnetic resonance imaging (Mri) technique, which fails to differentiate arteries and veins, uses an injected contrast agent, cannot detect the smallest vessels, and is time-consuming and costly. a new Mri technique called susceptibility weighted imaging (sWi) examines partially deoxygenated blood, allowing high-resolution images of tiny veins. further development is needed to improve these venograms and make them useable for image-guided neurosurgery. This development would involve using an existing image-processing technique to segment the veins. The result would be a venogram that could be imported into the image-guided neurosurgery platform that is used for both surgical planning and implementation. This approach could yield substantially better quality data at a lower cost without the use of an invasive agent.

outlookA second fMRI test based on the same principles as the first is being developed for patients who require a follow-up exam. It remains for a sufficient number of scans to be carried out on right- and left-temporal lobe epilepsy patients to create a typical profile of temporal lobe epilepsy. A future step will be to examine options for marketing the fMRI test.

progressA profile of memory function in the brain has been compiled based on scans of a large number of healthy subjects. The fMRI protocol for the epilepsy test is complete and ready for clinical testing.

summaryin temporal lobe epilepsy, brain regions important for memory are compromised.

The primary concern for these patients is whether their memory problems will

become worse following surgical intervention. for the medical team, information

about seizure lateralization and sparing of eloquent tissue are essential.

Dr. sziklas (right) and Dr. Jones-gotman (left) have developed a way to discriminate

between normally functioning and dysfunctioning memory structures during

a pain-free and relatively low-cost procedure: memory testing with fMri. The

method’s commercial application extends to epilepsy centres worldwide.

funded projects 2010-2011

research reports research reports

APPLIED NEUroSCIENCE AND CoMMErCIALIzATIoNtargeted research and development of resources for neuroscience and problems of the nervous system.

Peter mcPhersonThe MNI Antibody Resource for Neuroscience Research

antibodies (abs) are a critical resource for neuroscience research, but custom abs are costly to generate and have a high failure rate. Peter McPherson’s lab developed a novel hybrid approach for the production of epitopes used in custom antibody production, which simplifies and accelerates production. With cecr funding, a fully functional ab production facility has been established and is successfully producing and commercializing custom epitopes and antibodies for investigators at the Mni, Mcgill and outside Mcgill. in the 3 years since its inception, the ab centre of excellence (abcoe) has performed 115 projects for 13 investigators and 2 companies. The abcoe has so far generated over $71,364 in fees and $30,834 in royalty payments.

alyson fournierTargeting CRMP4b for Neuronal Repair

spinal cord injury is devastating in part because of the damage done to the central nervous system and because it is usually irreparable, consigning the patient to a lifetime of medical care. This is because the neurons and supporting cells are unable to spontaneously regenerate and restore functional communication in the central nervous system. alyson fournier’s team identified the role of a protein, crMP4, in inhibiting neuron outgrowth and designed a competitive inhibitor termed c4riP to attenuate the outgrowth inhibition. But there are many forks in the research road: the first application of c4riP in an optic nerve injury paradigm has been unsuccessful and the team has now engineered a modification – TaT-c4riP – with which to continue the research.

Philippe séguélaTRPC Channels as Therapeutic Targets in Neuropathic Pain

chronic pain affects the quality of life and productivity of millions of canadians. effective treatment is seldom available and the solution lies in better translation of basic research findings on pain mechanisms into innovative drug development. This cecr project is focused on the role of TrPc ion channels in the cellular mechanisms of chronic pain. The goals are to validate TrPc3 channels as pharmacological targets that modulate the sensitization of peripheral Drg neurons known to participate in inflammatory and neuropathic pain and, secondly, to control TrPc3 activity in vitro and in vivo.

Philip BarkerTargeting Neurite Growth Inhibitor Receptors to Promote Regeneration after Injury

The development of drugs that will enhance neuron repair after spinal cord injury remains one of the most sought-after research goals. This project brings together an impressive representation of the expertise available at the Mni with investigators experienced in biochemistry, signaling, cell-based models of neurite inhibition and preclinical models of spinal cord regeneration.

Gabriel leonardComputerized Device to Measure Simple and Complex Hand and Arm Movements

Tapping tasks that involve out-of-phase coordinated movements of the two hands are reliable indicators of motor skill that is impaired after damage to regions of the frontal lobes. With cecr funding, Dr. leonard has successfully created a computerized tapping apparatus, which is portable, easy to use and can now record and report all error types. it is sought after by clinicians and researchers and has application for pharmaceutical research. Maximizing commercial sales of the apparatus requires extensive norms, linkage with normative data from the old apparatus, reliability measures and brain-imaging corroboration. These aspects of the project are well underway; eight computerized machines have been produced and three assistants hired. Well over 1000 subjects (6 to 92 years of age) have been tested en route to a target sample of 2,000.

tim KennedyGeneration and Characterization of Novel Compounds to Inhibit Cell Migration

Dr. Kennedy and his team have identified a fragment of netrin-1 that inhibits cell movement, without the attractant functions of the full length protein. The goal of the current project is to synthesize peptides with this minimum sequence in order to develop compounds with favourable drug-like properties that could inhibit cell movement. Diseases in which abnormal cell migration is an important factor include the metastasis of tumour cells in various cancers, and the abnormal growth of blood vessels in diseases which are a leading cause of blindness. importantly, the lab has evidence that tumour cells and vascular cells have the receptors required to respond to the proposed compounds, indicating that they should have clinical utility.

amit Bar-or, david Colman*Identification of Novel Initiating Targets and Prognostic Markers of MS in Pediatric-Onset Disease

canadian children suffer one of the highest rates of multiple sclerosis (Ms) in the world. Ms is the leading cause of neurological disability in young adults in the Western hemisphere and is caused by repeated attacks on the central nervous system by the body’s immune system. although treatments are able to partially reduce attacks, doctors are unable to tell at the time of the first attack whether this is an isolated incident or whether it will progress into Ms. This project seeks to define the earliest molecular sites of the disease in order to identify biomarkers that can be used to predict the onset of Ms, and develop treatments best suited for early intervention.

*Deceased June 1, 2011

amir shmuelMonitoring Systems for MRI and Lab Environments

Dr. shmuel’s project specifically addresses common and costly issues in Mri- and lab-based research: recorded subject monitoring, the need to monitor any movement of the subject as to minimize blurs on the scan of alert subjects, and the need to assure an optimum anesthesia regime that will result in integrity of the data. To this end, Dr. shmuel, with the support of anesthesia-specialist Dr. gilles Plourde, developed three systems. The first system is a patient monitoring and data acquisition system for use in a regular lab and Mri scanner environment – there are currently four (4) fully functioning prototypes in use at The neuro. The second system is an Mri compatible system for monitoring subject movements in real time – there are currently two (2) functioning systems in use within Mcgill. By early fall 2011, system 2 will have been modified and will have an integrated infra-red camera. finally, the third system consists of the software that analyzes the data supplied by system 1. interest is already growing in these systems and options on how to commercialize them are being explored.

eric shoubridgeMolecular Diagnostics Laboratory for Neurological Deseases

a large number of neurological diseases are hereditary and identifying the genetic flaws allows for earlier diagnosis, selection of appropriate therapies and monitoring of disease progression. The Molecular Diagnostics laboratory offers unique genetic testing, adding to the Mni’s diagnostics capabilities as well as to its positioning as a leading-edge facility for neurological disease. To date, the lab has developed Dna-based tests for 18 different genes causing neuromuscular diseases; offers Dna based testing for all of the major disorders due to mutations in mitochondrial Dna; and is the only lab in north america to offer a biochemical test that provides a biochemical fingerprint of the respiratory chain defect. Due to changes made by the Quebec government effective april 1, 2011, billing for services between Quebec based hospitals is no longer permitted thereby limiting the ability to earn revenue. The lab is currently exploring various options including incorporating their services within an existing accredited clinical laboratory in the Mcgill system.

andrew readerScanner-Adaptive Image Reconstruction Platform for Accelerated Technology Transfer in Positron Emission Tomography

Dr. reader is creating an image reconstruction platform that is capable of handling data produced by different Positron emission Tomography (PeT) systems. This software permits the latest developments in image reconstruction technology to be applied to a wider range of PeT systems. The platform’s algorithms will allow image reconstruction, data correction and simulation for a range of PeT systems, all within a common framework. readily adaptable to any PeT system, the platform will facilitate further research developments in image reconstruction along with easier integration with other image-processing software. The platform aims to overcome the obstacles of adapting new reconstruction algorithms to a given scanner, opening up strong commercial potential.

CLINICAL TrIALS testing of medications and treatment devices for neurological disease in humans.

amit Bar-orExperimental Therapeutics Program

as a true expression of translational health research, the experimental Therapeutics Program (eTP) aims to bridge basic research in neurobiology and immunology with human studies of neurological and immune-mediated diseases. The program facilitates the translation of projects from the ‘bench’ to the ‘bedside’ through a range of activities with an overarching goal of expediting the development of emerging therapies for treating many neurological diseases. cecr funding has enabled the eTP to meet milestones in several areas such as the establishment of a state-of-the-art biorepository and generation of validated standard operating procedures (soPs), and has specifically supported the establishment of several platforms such as the luminex multiplex system and multi-color flow cytometry units that will also serve as core facilities to the Mni and external communities.

PUBLIC oUTrEACHeileen PetersonExpanding Neuro-Patient Resource Centre Outreach

The neuro-Patient resource centre (nPrc) provides information, both on-line and in print, on neurological and neurosurgical disorders and is accessed primarily by patients and their families. The nPrc focuses on identifying authoritative, current and evidence-informed information. The cecr funding has improved the services of the nPrc by providing the means to increase the centre’s opening hours to 54 hours per week, up from 35. This funding has also been used to employ graduate students to answer the increased number of reference questions and to improve and update the website. as a direct result, usage of the nPrc has doubled since 2008 with almost 8000 people accessing the services offered – 35% of these visits occur during the new extended hours. The website continued to have an average of 4,800 hits a month – an increase of 20% since 2008.

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funds from the cecr award have been allocated for educational and outreach activities. The investment of cecr funds has leveraged additional funds from the private sector and will lead to long-term educational benefits, including transferring knowledge and inspiring the next generation of scientists.

neuropolis (new working title “The Brain”)in collaboration with the national film Board of canada (nfB), The neuro continues to be involved in the develop-ment of a film and digital media project on the brain that will feature the work of scientists at The neuro and other universities and centres around the world. The Brain Project is designed to spark curiosity in a new generation of young people and to inspire their excitement about science, and particularly neuroscience.

neuro scientists have participated in more than one hundred hours of interviews that serve as background for the project. currently film treatments and digital approaches to the material are being explored.

award-winning talent is engaged in The Brain Project and partners across the film and digital media industry are helping to bring this vision to reality.

as an extension to the film, the Mni engaged a game developer to create a game on brain activity that could be sold as an apple application.

Media relations, Public outreach and educationThe television ad produced with the support of cecr funds in year one (1) has been used to leverage donations of national ad space worth approximately $3 million to date, including an additional commitment of $1.3 million from astral Media bringing their total to support to $2.3 million. in the summer of 2010 we began a pro bono partnership with the Montreal communications firm Bos to develop a new branding and marketing strategy designed to raise awareness for The neuro and the role of neuroscience in our lives.

Development of a web-based database of researcher activity at the Mni The Mni has established a database of various activities of all Mni researchers including their publications, partnerships, collaborations, students, trainees and commercial activities. an on-line interface to facilitate access to the information is being developed and will be accessible to the Mni research community. The cecr Program and internal review committee will evaluate rendering the database accessible to outside research communities.

institute and international fellows ProgramThe cecr fellowship is a two-year fellowship that supports research and study in clinical and basic neuroscience. a total of 15 fellowships were awarded between 2008 and 2010. in 2010-11, we supported eight (8) post-doctoral fellows with awards of $40,000 per year. several former cecr post-doctoral fellows have gone on to accept research and academic positions in countries around the world including china, france, and switzerland.

Mcgill integrated Program in neuroscience and student rotation ProgramThe Mcgill integrated Program in neuroscience (iPn) is an initiative and expansion of the graduate Program in neuroscience. The iPn is in line with Mcgill university’s emphasis on neuro-science and its strategic plan to attract top graduate students. it is the largest graduate program in the faculty of Medicine and one of the largest neuroscience graduate programs in north america.

Mcgill has a high concentration of neuroscientists, but they are spread throughout different departments, hospitals and research institutes across Montreal. The iPn is a multi-disciplinary, inter-departmental program that brings together all graduate training in neuro-science currently under the Mcgill umbrella, and offers prospective students a single consolidated program through which to apply for and attain their Msc or PhD in neuroscience. The program currently comprises 160 faculty and almost 300 graduate students. all aspects of the student experience, including the program’s website; application and supervisor selection procedures; tracking the attainment of milestones; and student awards, were evaluated and improved when the iPn was introduced.

a new feature of the iPn is a rotation Program for outstanding students who wish to try their skills in several different laboratories for their first year, before committing to a supervisor for the rest of their graduate work. The first six (6) students in our rotation Program are set to complete their rotation in fall 2011 and five (5) new students will begin in fall 2011.

public outreach and engagement activities

“i chose to participate in the iPn rotation Program because i wanted to expose myself to the wide range of neuroscience research at Mcgill and establish relationships that i can draw on for future collaborations”.

Liu (Dave) Liu, IPN Rotation Student 2010-2011

“The rotation program was an excellent opportunity to challenge myself, to maximize my learning experience at Mcgill, and to really determine what kind of research i wanted to do”.

Sarah Konefal, IPN Rotation Student 2010-2011

“This helped me refine my own research interests and led me to a lab that i had not really considered before entering the program”.

Avinash Vaidya, IPN Rotation Student 2010-2011

“The rotation program was a tremendous experience that i would recommend to anyone interested in pursuing a neuroscience doctoral degree from Mcgill”.

Phil Dickinson, IPN Rotation Student 2010-2011

“i have a broader view of neuroscience now and this knowledge is relevant when i go to conferences or speak with other scientists”.

Ariane Gagnon, IPN Rotation Student 2010-2011

“i was drawn by the excellent reputation of the Mni and the rotation program was a key factor in my application to the iPn.starting directly in a single lab would not have given me the knowledge, experience, confidence or ability to plan and undertake my PhD project, and i am grateful for the opportunity provided by the Mni and the cecr.”

Nasr Farooqi IPN Rotation Student 2010-2011

integrated Program in neuroscience retreat (september 20-21, 2010)The 2010 integrated Program in neuroscience (iPn) retreat was an opportunity for Mcgill researchers from all disciplines of neuroscience to come together and share their work interests with one another. attendance at the two-day event was mandatory for all new students admitted to the iPn, and personnel from iPn labs were also invited. 430 people pre-registered for the retreat and an additional 50 registered on-site. With poster sessions (~70 posters), overview talks and themed sessions, Mcgill’s contributions to the world of neuroscience research were showcased at the retreat. scheduled activities encouraged inter-action among students, postdoctoral fellows and principal investigators and represented the full depth and breadth of Mcgill neuroscience. The next annual iPn retreat will be held september 20-21, 2011.

Liu (Dave) Liu, Phil Dickinson, Avinash vaidya, Sarah Konefal and Ariane gagnon (missing from photo: Nasr Farooqi).

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industry partnersThe Mni has a long history of partnerships with industry and lists a number of major companies in its collaborations. among them are the following:

• Archemix Therapeutics• AstraZeneca• Aventis• Biogen Idec• GE Medical Systems• Genentech• Lantheus Medical Imaging • MediMabs• Medtronic• Millennium Pharmaceuticals• Millipore• Neuromics• PainCeptor Pharma• Proportional Technologies Inc.• Takeda Pharmaceuticals Inc.• Teva Neuroscience

as well, Mni investigators founded several companies as part of their technology and knowledge transfer initiatives:• Aegera Therapeutics• Biospective• PainCeptor Pharma• Stellate

The projects funded through the cecr award have enabled further collaborations with industry. in 2010-2011 collaborations have been confirmed with AstraZeneca, caprion Proteomics, Millipore, labopharm, siemens and The centre for Drug research and Development.

Patent applicationsresults of seven (7) cecr-funded projects since 2008 are the object of patent applications:

alyson fournierTargeting crMP4b for neuronal repair– national phase in canada, the united

states, europe and Japan

Philip BarkerTargeting neurite growth inhibitor receptors to promote regeneration after injury– lgi1: national phase in the united states

tim Kennedygeneration and characterization of novel compounds to inhibit cell migration– netrin: Provisional patent application filed

in the united states– Patent cooperation Treaty (PcT) patent

application filed (2009-2010)

amit Bar-or / david Colman*Pediatric Ms biomarkers– cadherin: Proof of concept stage– national phase in canada, the united

states and europe (2009-2010)– Patent application filed*Deceased June 1, 2011

Gabriel leonard a new computerized device to measure simple and complex hand and arm movements– Provisional patent application filed

in the united states (2009-2010)– Patent cooperation Treaty (PcT)

international patent application filed (2010-2011)

ralf schirrmacher (2009-2010)imaging innovation and translation(Bruce Pike)– Thiol-nota Derivatives for Kit68ga

radiolabeling: Patent cooperation Treaty (PcT) patent application filed

– ligands for Targeting Pancreatic alpha and Beta cells: Patent cooperation Treaty (PcT) patent application filed

Kevin Petrecca (2010-2011)Translating Drr into a therapeutic target to prevent brain cancer invasion– Provisional patent application filed

revenues generated from commercial activities in 2010-2011Peter mcPhersonThe Mni antibody resource for neuroscience research $102,198

eric shoubridgeMolecular Diagnostics laboratory for neurological Diseases $27,994

revenues generated from core services in 2010-2011amit Bar-orexperimental Therapeutics Program$734,382

Bruce PikeMcconnell Brain imaging centre$2,477,963

thomas strohMicroscopy core services$30,615

commercialization and business development

in year 4, we will continue to maintain the objectives that were part of the long-term strategy originally defined in 2008-2009 and to ensure the effective use of the cecr award.

as per the funding agreement, the remaining funds of the $15M cecr grant were committed in year 3.

for year 4 we requested that all recipients with monies remaining in their respective project funds, submit a description of their progress to-date, including reasons for project delays, if applicable; justification for extending their funding end-date beyond May 31, 2011; and a revised time line. recipients whose funding end dates are extended, will again be mandated to provide quarterly project progress updates via the on-line system that was developed in the first year of the program.

Projected unspent committed funds* for 2011-12 are defined as follows:

Mni corporate plan 2011-2012

* as per article v, section 5.1, of our funding agreement all funds were committed by March 31, 2010.

inVestiGator initiated ProGrams

Biological basis of neurological disease, early stage commercialization $ 408,476

neuroengineering $ 122,232

Translational neuroscience $ 612,456

applied neuroscience and rapid commercialization $ 164,081

clinical trials support $ 50,370

PuBliC outreaCh and enGaGement

fellowship Program $ 88,305

Mcgill integrated neuroscience Program $ 167,597

Media relations and outreach $ 157,851

intellectual property protection and business development $ 277,743

opportunity fund $ 467,316

administration $ 167,815

totAl $2,684,262

our short term goals for 2011-2012 focus on reviewing year 4 renewal requests, meeting with our cecr advisory Board and confirming year 4 funding. our medium term goal is to facilitate the growth of the commercial ventures that have been initiated, with the establishment of appropriate management and oversight and governance structures for these entities.

“our CECr grant allowed us to develop a new method of high-throughput screening for channel blockers that led to an active collaboration with the Centre for Drug research and Development (CDrD) in vancouver.”

Philippe séguélaTrPC Channels as Therapeutic Targets in Neuropathic Pain

“The CECr grant to the Neuro-Patient resource Centre allowed us to keep the resource Centre open longer hours during the week and to stay open on Saturdays. These extended hours allowed us to provide better access to our materials and computers. we were able to answer more patient and family information questions, and keep our website updated. The results were a 70% increase in the use of the Centre by patients and families and a 20% increase in visitors to our website. A by-product was that we provided 8 graduate students in the MLIS program a top-notch experience in providing excellent, compre-hensive library services.”

eileen PetersonExpanding Neuro-Patient resource Centre outreach

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financial statements statement of revenue and expenses and funds available

indePendent auditor’s rePort

To the management of the royal institution for the advancement of learning

at the request of the royal institution for the advancement of learning (Mcgill university) (the “university”), of which the Montreal neurological institute of Mcgill university (the “institute”) is a department, we have audited the statement of revenue and expenses and funds available for the period from June 1, 2010 to May 31, 2011 (the “statement”) of the institute. The statement has been prepared by management based on the funding agreement signed with the Minister of industry.

management’s responsibility for the statement

Management is responsible for the preparation of the statement in accordance with the funding agreement signed with the Minister of industry, and for such internal control as management determines is necessary to enable the preparation of the statement that is free from material misstatement, whether due to fraud or error.

auditor’s responsibility

our responsibility is to express an opinion on the statement based on our audit. We conducted our audit in accordance with canadian generally accepted auditing standards. Those standards require that we comply with ethical requirements and plan and perform the audit to obtain reasonable assurance about whether the statement is free from material misstatement.

an audit involves performing procedures to obtain audit evidence about the amounts and disclosures in the statement. The procedures selected depend on the auditor’s judgment, including the assessment of the risks of material misstatement of the statement, whether due to fraud or error. in making those risk assessments, the auditor considers internal control relevant to the entity’s preparation of the statement in order to design audit procedures that are appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the entity’s internal control. an audit also includes evaluating the appropriateness of accounting policies used and the reasonableness of accounting estimates made by management, as well as evaluating the overall presentation of the statement.

We believe that the audit evidence we have obtained is sufficient and appropriate to provide a basis for our audit opinion.

opinion

in our opinion, the statement of the institute for the period from June 1, 2010 to May 31, 2011 is prepared, in all material respects, in accordance with the university’s reporting requirements under the funding agreement signed with the Minister of industry.

Basis of accounting

Without modifying our opinion, we draw attention to the accounting policy in the statement, which describes the basis of accounting.

september 9, 2011 1 chartered accountant auditor permit no. 22220

samson Bélair/deloitte & touche s.e.n.c.r.l.

1 Place ville Marie suite 3000 Montréal Qc h3B 4T9 canada

Tel: 514 393-7115 fax: 514 390-4116deloitte.ca

mcGill uniVersitY fundinG aGreement With the minister of industrY

statement of revenue and expenses and funds available for the period from June 1, 2010 to May 31, 2011

funds available, beginning of year $7,833,343

revenue

interest 6,784

expenses

salaries 2,829,711

fringe benefits 385,178

Material and supplies 681,347

contract and consultant services 225,858

Travel 68,038

equipment 76,280Miscellaneous 180,135

4,446,547

excess of expenses over revenue 4,439,763

funds available, ending of year $3,393,580

With respect to our funding agreement, the cecr award was not used to fund executive or senior member salaries (article 8.2.e.i) nor was it used for employee salaries exceeding $100,000 (article 8.2.e.ii).

accounting policy

The statement is presented using the accrual basis of accounting and was prepared in accordance with the funding agreement signed with the Minister of industry.

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The following projects and initiatives were accepted by the Mni cecr Program and internal review committee for funding in 2010-2011. The committee complied with Mcgill university’s regulation on conflict of interest in the evaluation of proposals submitted for Mni cecr funding and in decisions with respect to funding of projects.

cecr initiatives and funding

inVestiGator BioloGiCal Basis of neuroloGiCal disease fundinG

Michael Petrides Atlas of the human cerebral cortex $100,000

Barry j. Bedell PIA -ArACHNoID – Platform for Integrated, Advanced Animal research for Complex Human Neurological, oncological and Inflammatory Diseases

$150,000

Edward Fon The cell biology of Parkinson’s Disease $ 75,000

Philip Barker The joint MNI – BrI Protein Production Facility $ 75,000

Thomas Stroh Microscopy Core Services $130,000

Eric Shoubridge resource for the generation of induced pleuripotent stem cells $ 70,000

inVestiGator neuroenGineerinG fundinG

Eliane Kobayashi Application of Magnetoencephalography in the Assessment of the Epileptic Focus $ 90,000

Andrea Bernasconi Automated Lesion Detection in Pharmacoresistant Epilepsy $ 80,000

inVestiGator aPPlied neurosCienCe and CommerCialization fundinG

Peter McPherson The MNI Antibody resource for Neuroscience research $ 50,000

Eric Shoubridge Molecular Diagnostics Laboratory for Neurological Diseases $150,000

Alyson Fournier Targeting CrMP4b for Neuronal repair $ 68,100

Philippe Séguéla TrPC Channels in Neuropathic Pain: from Cellular Physiology to Novel Therapeutic Targets $100,000

Philip Barker Targeting Neurite growth Inhibitor receptors to Promote regeneration after Injury $ 75,000

gabriel Leonard A New Computerized Device to Measure Simple and Complex Hand and Arm Movements $130,500

Tim Kennedy generation and Characterization of Novel Compounds to Inhibit Cell Migration $119,267

Amir Shmuel Monitoring Systems for MrI and Lab Environments $128,000

Amit Bar-or David Colman*

Identification of Novel Initiating Targets and Prognostic Markers of MS in Pediatric-onset Disease

$150,000

Louis Collins Development of MrI Tool to Facilitate the Development of Drugs to Treat Prodromal Alzheimer’s Disease (MCI)

$ 85,050

Andrew reader Scanner-Adaptive Image reconstruction Platform for Accelerated Technology Transfer in Positron Emission Tomography

$100,000

viviane Sziklas A Cost-Effective fMrI Solution to replace Invasive Examination of Medical Temporal Lobe Functions

$ 84,420

inVestiGator translational neurosCienCe fundinG

william Feindel Cost-effective Analysis of the Montreal Procedure for Surgical Cure of Temporal Lobe Seizures

$ 40,000

Alain DagherAmir Shmuel

Early Diagnosis of Alzheimer’s and Parkinson’s Diseases $125,000

Bruce Pike Imaging Innovation and Translation $500,000

Amir Shmuel Clinical Applications of Non-invasive Manipulation of Neuronal Excitability $100,000

Denise Klein Pre-surgical Functional Brain Mapping Unit $110,000

Marilyn jones-gotmanLesley FellowsAlain Ptito

The MNI Cognitive Neuroscience Testing resource $ 0**

Kevin Petrecca Translating Drr into a Therapeutic Target to Prevent Brain Cancer Invasion $ 80,000

Bruce Pike Mr venography for Image guided Neurosurgery $ 57,500

inVestiGator CliniCal trials fundinG

Amit Bar-or Experimental Therapeutics Program $250,000

manaGer outreaCh and enGaGement fundinG

Thomas gevas Institute and International Fellows Program $140,000

Thomas gevas Mcgill Integrated Program in Neuroscience $ 60,000

Sandra McPherson Media relations, public outreach and education $255,000

Eileen Peterson Expanding Neuro-Patient resource Centre outreach $ 25,000

manaGer neW oPPortunities fundinG

David Colman* opportunity Fund*** $235,000

manaGer intelleCtual ProPertY and Business deVeloPment fundinG

Thomas gevas Intellectual Property Protection and Business Development $300,000

manaGer administration fundinG

David Colman* Administration Costs $100,000

* Deceased June 1, 2011 ** Project renewed but no new funding allocated as there were sufficient funds remaining from year 2. *** Pursuant to the submission of the 2009-2010 corporate Plan and based on the experiences in the first year of the cecr award, a portion of the cecr award was reserved for outstanding initiatives that emerged over the course of the year.

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cecr advisory BoardMandate

• To provide global oversight to ensure that the Mni centre of excellence in com-mercialization and research award meets the goals and terms of the agreement and that funding initiatives align with Mni strategic goals.

Activity

• The board met twice.

• Reviewed and approved the 2009-2010 cecr annual report.

• Reviewed and approved budget allocations for 2010-2011 and for the 2011-2012 budget.

• Provided advice to be implemented in year 3 related to increasing commercialization potential.

MembershipJacques Bougie, o.C.chair, cecr advisory Boardchair, The neuro advisory Boardformer President and chief executive officer,alcan aluminium inc.

max fehlmann, Phd, mBaPresident and ceo,Québec consortium for Drug Discovery (cQDM)

Gregory orleski, B.a., ll.B., B.C.l.vice-President, Business Development,labopharm inc.Board member, The Maisonneuve-rosemont hospital foundationBoard member, Pediapharm inc.

cecr Program and internal review committeeMandate

• To ensure that the MNI’s Centre of excellence in commercialization and research funding decisions are consistent with goals outlined in the federal science and Technology strategy.

• To ensure that funding is allocated to high priority projects and distributed in a responsible manner.

• To evaluate proposals using criteria outlined in the competitive phase of the Mni centre of excellence in commercia-lization and research Program.

Activity

• The executive members of the committee met twice.

• Reviewed Year 4 applications and forwarded funding recommendations to the cecr advisory Board for approval.

Membershipmartine alfonso*administrative Director, neuroscience MissionMcgill university health centre

amit Bar-or, mdDirector, experimental Therapeutics Program and coordinator, clinical research unit, Mni

Philip Barker, Phd*chair, cecr Program and internal review committeeassociate Director for strategic initiatives, Mni

robert dunn, Phdassociate Director, scientific affairs, Mni

thomas Gevaschief financial officer, Mni

elizabeth Kofron, Phdassociate Director, corporate affairs and special Projects, Mni

Peter mcPherson, Phdcoordinator, cell Biology of excitable Tissue, neurobiology unit, Mni

Bruce Pike, PhdDirector, Mcconnell Brain imaging centre, Mni

eric shoubridge, PhdDirector, Molecular neurogenetics, Mni

david sinclair, mdneurosurgeon, Mnh

cecr commercialization committeeMandate

• To review and advise on all potential commercial activities and charged with identifying the most promising technologies, providing input into intellectual property protection and developing commercialization strategies.

• To ensure that projects with commercial potential/aspects are provided the necessary tools/aids to avert failure.

Activity

• Individual members of the committee met with several cecr funded researchers to discuss and provide professional support regarding the potential commercial advancement of their cecr funded projects.

MembershipPhilip Barker, Phd*chair, cecr Program and internal review committeeassociate Director for strategic initiatives, Mni

thomas Gevaschief financial officer, Mni

timothé huot, ll.l.lawyer, Bcf

donald olds, msc, mBachief financial officer & chief operations officer,aegera Therapeutics inc.

emma saffman, PhdPatent agent, norton rose or llP

michael stern, Phd commercialization officer, office of sponsored research,Mcgill university

Patrick tremblay, Phdexecutive-in-residence, Pappas ventures

*interim Directors Mni as of June 23, 2011

governance

investigators

BioloGiCal Basis of neuroloGiCal disease

Philip BarkerBarry J. Bedelledward fonMichael Petrideseric shoubridgeThomas stroh

translational neurosCienCe

alain DagherWilliam feindellesley fellowsMarilyn Jones-gotmanDenise KleinKevin PetreccaBruce Pikealain Ptitoamir shmuel

neuroenGineerinG

andrea Bernasconieliane Kobayashi

Clinical trials

amit Bar-or

aPPlied neurosCienCe and CommerCialization

amit Bar-orPhilip Barkerlouis collinsDavid colman*alyson fournierTim Kennedygabriel leonardPeter McPhersonandrew readerPhilippe séguélaamir shmueleric shoubridgevivian sziklas

PuBliC outreaCh

eileen Peterson

students

Mirza abdel Baigfahd al-sybaiesilvain BeriaultBoris BernhardtJulie BoyleMegan callahansean chenguillaume cloutierDuncan cowieDebbie DawsonXue fenghalleh ghaderiKristina goodwinstephanie harrisseokjun hongMaria ioannouJahan Jadaujiahmad Kanaanhosung KimJulia KleinbergPascal KropfXiang lurobyn MalerThomas Mansisteven c. MatosJames Mcnicolandrea Miller-nesbittsujaya neupanPamela ngstephan ong Tonelisa Palladinirenata Podbielskielouise Ptitoemily segalMartha shiellJiwon shinajay venkateswaranZe Shan YaoVeronika Zlatkina

Postdoctoral fellows

anshul awasthisarah Bankssarah BurnsJen-Kai chensophie colnatDong hanMohammad Khazaeiroberta laPianalaurence Merciershmuel na’amanManuel Porras-BetancourtDominique rosenbergXi shenEhsan Sherafat Kazem ZadehTaner Tanriverdiisabelle Thiffaultsebastien ThomasMarcelo valencaJeroen verhaegheJessie r. WeberZizhen Zhang

* Deceased June 1, 2011

cecr investigators, students and postdoctoral fellows

The Mni cecr advisory Board, the Program and internal review committee, and the commercialization committee ensured, through their respective mandates, that management of the Mni cecr award is efficient, fair and transparent, and that funding is used towards stated objectives.

“CECr funding has been an enormous success for the McConnell Brain Imaging Centre as it has created fertile ground for innovations with significant commercial potential such as automated medical image analysis techniques and new molecular imaging probes. The Centre has now spawned numerous very successful high tech start-up companies, based in Montreal, that employee well over 100 highly qualified personnel.”

Bruce PikeImaging Innovation and Translation

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