Treating Cystic Fibrosis

8/6/2019 Treating Cystic Fibrosis

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TREATING CYSTICTREATING CYSTIC

FIBROSISFIBROSIS



Introduction

4 ways

ØPhysiotherapy

ØDiet and enzymes

ØDrug therapies

ØTransplant surgery

ØInfertility treatments.



PHYSIOTHERAPY

Remove as much mucus from the lungs aspossible

Easier to breathe – enough oxygen Reduces risk of lung infection Done couple times a day – depending on the

severity of CF New device – changes the pressure in the

airways, help people to clear their mucus –

w/o vigorous physiotherapy E.g.: ‘Flutter’ the positive expiratory pressure

(PEP) and thAIRapy – bronchial drainagesystem.



Images



DIET AND ENZYMES

Thick mucus – block pancreatic duct –digestion and absorption of food is bad

Overcome – CF patients – take enzymes –

replace the missing pancreatic enzymes –food can be digested

Carefully balanced diet – eat more than normalpeople – need more high energy food, highfat, high carbohydrate foods, adults musttake twice the amount of proteins.



DRUG THERAPIES

Usually take many medication –cocktailAntibiotics - tobramycin solution for inhalation

Vaccines

Mucolytic - Pulmozyme® to thin mucus sopeople can cough it out easier.

Asthma drugs – salbutamol and steroids

DNAase enzymes

Insulin



TRANSPLANT SURGERY

LUNG – cannot function properly – heart also affected – only way is through a transplant of lung and heart

New organs – not affected by CF – other parts will stillbe affected

After transplant – person takes –IMMUNOSUPPRESSANT drugs – for whole life –avoid body reacting against the new tissue andrejecting it.

Suppresses immune system – makes it harder for the

body to fight infections However – most people receiving transplant usually

do well



INFERTILITY TREATMENTSWomen having CF – have increasingly

had babies

Need to use – IVF – some – reproductive

system is not badly affected.Men – techniques – taking sperm from

the testes and using it – fertilize eggsin vitro – embryos formed – returned tothe mothers uterus to developnormally.



GENE THERAPYGENE THERAPY



INTRODUCTION

CF Treatments – aims to removesymptoms entirely / cure

Hope – to replace the recessive allele

with a healthy allele = GENETHERAPY

GENE THERAPY – involves taking acopy of the healthy gene and findingan effective way of getting it into thecells that need it – to produce thecorrect protein.



COPYING THE HEALTHYGENECopying and inserting genes – genetic

engineering / genetic modification =first stage of gene therapy

Use special enzymes – restrictionendonucleases – cut healthy DNAstrands into specific sites.

Enzymes – cut DNA – easier to handle –

each endonucleases – specific –restricted sites on DNA – that’s howthe get the name!



COPYING THE HEALTHYGENE Artificial copies of the healthy gene –

made – mRNA – transrcibed – use toproduce correct DNA sequence –

reversing the transcription process –using enzyme – reverse transcriptase

DNA made from this – known as –complementary DNA (cDNA)

Since we know CFTR base sequence –make these base pairs in labs.



VECTORS

Next stage – attach isolated gene toanother piece of DNA – VECTOR

PLASMIDS – circular strands of DNA

found in bacteria – used as vectors Plasmids combine with the cell’s DNA –

forms – RECOMBINANT DNA

Other vectors are needed to carry newDNA to human cells – CF – tested withharmless viruses and liposomes







Once healthy gene – inside the lungs –the genes should transcribed andtranslate into producing – NORMAL ,ACTIVE CFTR PROTEINS – relievingthe symptoms

BUT! : practice has shown that it is noteasy to do so.



GENE THERAPY INGENE THERAPY IN

CYSTIC FIBROSISCYSTIC FIBROSIS



GENE THERAPY IN CF

Mutated gene – chromosome 7 – isolated – 1989

By 1990 – normal gene – copied and

added to cells affected by cystic fibrosisin lab – proven effective

Begin human studies – used both virus

and liposomes – limited success – notenough to relieve symptoms of thedisease







1. EXTRACELLULARBARRIERSMany barrier to overcome – new DNA –

vector – reaches epithelial cells

? – because CF blocks airways – difficult

for spray to penetrate the lungs,surface is coated with thick stickymucus.

Ways – dilute mucus-Mucolytic/DNAase

– trying different routes – get vectors tolungs through the blood.



2. INTRACELLULARBARRIERS Vector – inside the cell – to get DNA to the

correct place Proved to be very difficult – especially when

liposomes are used as vectors 1/1000 plasmids that enter the liposome gets

to the nucleus to be transcribedResearch – focuses on – modifying the

vectors to get the new genes into the nucleimore effectively Viruses – gives best results!



3. KEEPING THE GENEEXPRESSION GOINGOnce inside the nucleus – transcribed –

problem – it does not work for long – 2weeks at best!

Research looking at ways to extend thisand make it permanent by usingdifferent vectors

Repair the faulty allele on the original

DNA itself – if stem cells could be used – lead to permanent cure.



CONCLUSION

The hope for gene therapy is that people will notneed treatment after initial medication

Quality of life and expectancy – improved with

no respiratory complications Big financial saving without lifelong treatments

Treat effects of the gut from the disease in thesame way

It is hoped that by 2009 – 2010 that human trialwill be underway again, possibly on a larger scale than before!



THE ENDTHE END

THANKTHANK

YOU ! YOU !

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Treating Cystic Fibrosis