Wearable HATH-1 Auditory Therapy:

Total Hearing Effect?Michael DeSalvio, John Chi, Michael Nguyen, Kevin Ip,

Khine Win

WHAT: THE?

John Chi – Electrical Engineer: System architecture, Software design

Michael J. DeSalvio - Molecular Biologist: Interface design, Biocompatibility

Kevin Ip - Molecular Biologist, Regulatory Contact

Mike Nguyen – Molecular Biologist and Lab Specialist: Drug delivery design, GLP contact

Khine Win – Material Science and Engineering: Fluid transport design, process fabrication

We are not researchers, we are designers!

Problem

Most hearing loss is caused by damaged cochlear hair cells, which do not regenerate

Hearing loss now affects 1 in 5 American teenagers (JAMA, 8-17-2010)

15% of adults between 20-69, 26 million adults, suffer from noise-induced hearing loss (NIHL, National Institute on Deafness and Other Communication Disorders)

25-40% of 60+ in US is hearing impaired - worsening (Yueh et al, 2003)

Current Solutions

Cochlear Implant

Hearing Aids

Underlying cause not addressed (hair cell destruction)

Cochlear Implant

• FDA approved in 1984

• Approximately $40,000 for procedure

• As of 2009, 188,000 worldwide received implants. (Davis, J 2009 Peoria Journal)

• Cochlear Implants rely on electrical connections to auditory nerve, destroying existing structures in the ear

• Infection, physical damage to unit, wear and tear (permanent)

• Developed by Cochlear Limited Australia, Advanced Bionics, Cochlear Corporation, Med-El, etc.

Hearing Aid

Removable prosthetic

Many different shapes and sizes

$150 to $5,000

Many different manufacturers and designs

No surgery

Can be bulky and cumbersome

Need constant adjustment (feedback, loud noises)

HATH-1 Therapy

Math1 allows transdifferentiation of cochlear cells into functioning auditory hair cells

These transgenic cells shown to be stable and growing after 10 weeks with significant restoration of auditory function (2003, Izumikawa)

Need multiple injection sites

Need to distribute throughout cochlea using micropump to optimize hair cell regeneration densit

HATH-1 Effectiveness

Routes of Entry

Two routes of entry into ear Systemic Route: drug circulates through blood

stream Local Application to inner ear (targeted drug

delivery)

www.gizmowatch.com

Device

Microfluidic circulating pump delivers drug safely to delicate cochlear region

Intracochlear drug delivery device to deliver chemotherapy

Built-in Piezoelectric ABR testing

Extracochlear stimulation maintains auditory regions in brain

FDA Class 2 Device and Class 2 Software

Prototype (Animal model)

Advantages

Does not destroy vestibular structure

Temporary prosthetic surgical solution

Permanent hearing restoration

No need for post-treatment prosthetic

Monitored treatment developmet

Maintenance is almost identical to existing cochlear implant

Disadvantages

• Suppress vestibular (balance) system function—with sometimes only minor effects on hearing.

• Risk of developing meningitis

• General risk of infection

• Cost: $45,000- $150,000 total cost

Where and When

Business location local to Southern California

Group competencies allow most development to take place in-house

Approximately 3 years to market with drug delivery device Milestone 1 – Develop prototype Milestone 2 – 510K Registration with FDA Milestone 3 – Commence clinical trials Milestone 4 – Complete clinical trials

How does it work?

• Delivering Hath 1 transcription factor and other drugs

• Microfluidic pump system with inlet and outlet tubule for delivery

• Use of intracochlear imaging system to monitor distribution of delivered substances

• Use of Extracochlear stimulation during recovery period

• 10 week treatment course

Khine Figure: Prototype (Human Model)

How is it Different?• Does not remove vestibular hair cells

http://www.surgeryencyclopedia.com/Ce-Fi/Cochlear-

Implants.html

• Can monitor hair cell growth through non-invasive ABR testing

• Higher distribution of delivered substances compared to delivery

through RWM

• Extracochlear stimulation does not destroy cochlea as opposed to

intracochlear device

Cochlear Anatomy

Contains two & three quarter turns (Basal, Middle & Apex)

3 fluid filled spaces located in parallel

scala vestibuli, tympani & cochlea duct

Fluid contains ionic compositions of Na+, K+, Ca2+ & Cl- (Endolymph & Perilymph)

Surgery

Surgery

Opening in the basal turn is made

Carbide micro drills modified fitted with insertion stops

Medical grade adhesive & dental cement are used

Almost identical to already used implant surgery

System Overview

Extracochlear Stimulator

• Can re-stimulate portions of the brain responsible for hearing even after prolonged “atrophy.” Documented patient Baron Jack Ashley, UK House of Lords

• Can improve hearing after complete deafness

• Reliable and efficient, long life cycle

• Restore hearing without damaging structures in ear canal

Michael N

Fluid Transport System (overview)

Microfluidic pump

Inlet tubule +

precision thermal flow sensor

Reservoir(contains Artificial

perilymph solution)

outlet tubule +

precision thermal flow sensor

Ear

Microcontroller

Fluid Transport (Materials)

Polyetheretherketone (PEEK) tube

Biocompatible

Excellent mechanical and thermal resistance

Good for application require vacuum environment

ISO 10993 standard & fully USP Class VI, FDA, NSF and European Pharmacopoeia criteria

Fluid Transport (Materials)

Polyetheretherketone (PEEK) tube

Biocompatible

Excellent mechanical and thermal resistance

Good for application require vacuum environment

ISO 10993 standard & fully USP Class VI, FDA, NSF and European Pharmacopoeia criteria

Fluid Transport

Precision thermal sensor

Utilizing temperature shift caused by fluid flow

Relationship between temp and volume of fluid flow

Microfluidic pump

Nano Liter application

Zero net transfer

Continuous inflow and outflow (not reciprocating

QFD – Power Subsystem

QFD – Power Subsystem

QFD - Battery

Input

Tubing Materials

Microprocessors

Casing Materials

Drug

Sensors

Circuitry

Pumps

Software and updates

Change Over Time

Wearing of pumps

Degradation of tubing

Degradation of drug

Circuitry corrosion

Loosening of delivery template

Degradation/loosening of seals

Degradation of battery

Wear on moving parts

Degradation of synthetic endolymph

Bodily immune response

Noise

External heat/cold

Water/humidity

Leaking

User opens device

Device falls off

Blunt force trauma

Bubbles in fluid line

Flow regulation failure

Electromagnetic interference

Intracochlear tissue

Internal heating

Battery failure, leaking

Charging mechanism seizes

Particulates in fluid line

Software bugs

Overheating

Accumulation of biofilm

Control Factors

Water tight seals

Flow rate sensors

Heat sensors

Pressure sensors

Electromagnetic shielding

Ultrasonic agitator for fluid lines, bubble trap

Redundant systems (firmware, tubing, pumps)

Sealed battery compartment

Accessible internal components for servicing

Use biologically inert materials

Consistent software reviews

Reversible flow – self backflushing

Simulation environments

Error States

Cooked/frozen drug

Short circuit

Clogged pump mechanism

Premature emptying of drug reservoir

Seizure of motor

Cracked casing

Water infiltrates system

Infection

Memory/firmware failure

Device fails to charge

Ideal Function

Correct dosage

Distribution of drug

Motors powered correctly

Body accepts implant

No leakage

ABR measurement of intracochlear cell restoration

Healthy cochlea, restored hearing

Summary

Site specific target allows for precise calculation of dosage

Targeted drug delivery which mitigates drug exposure to other tissues (HATH-1 effects in body)

Can be used for middle ear cancers and tumors

Can be used in conjunction with surgery to deliver antibiotics

No additional equipment or maintenance once treatment is complete

Questions?