RECENT ADVANCES IN GENETIC MANIPULATION IN THE TREATMENT OF CONGENITAL DEAFNESS
- Attempt to reverse certain types of defect that affect the early development of the auditory and vestbular systems
- Target group for screening: premature newborns and strong family history
- Technique to locate the gene on particular chromosome or the mutation within the gene and the gene product.
- Attractive technology for clinical applications
- It offers the hope for preventing, arresting , reversing or curing vestibular or hearing disorders caused by heriditary disease or environmental insults.
- In utero gene transfer has many technical and ethical issues.
- Vectors successfully studied are:
- cationinc liposomes
- adeno associated virus
- adeno virus
- lenti virus
- herpes simplex virus and
- vaccinia virus
VECTOR DELIVERY SYSTEM:
- Systemic administration: it has a disadvantage of systemic toxicity includng viral hepatitis and enchepalitis.
- Direct instillation:
- Allows high vector concentration delivery to target organ
- Needs small amount of vector solution
- Increase likelyhood of gene delivery to target tissue
- Minimizes leakage of vector to the surrounding.
Several techniques of intracochlear vector delivery are:
- Miniosmotic pump infusion or microinjection into scala tympani via round window
- Infusion or microinjection into the scala tympani through cochleostomy
- Injection into endolymphatic sac accessed from posterior fossa and
- Gel foam application to round window membrane.
Transgene expression in contralateral, noninjected cochlea occurs. Three potential routes of spread from cochlea have been suggested:
- Viral spread via cochlear aqueduct ehich connects scala tympani of basal turn of the cochlea to the CSF space
- Transmission of vectors through the temporal bone marrow space
- Haematogenous dissemination
STEM CELL AND GENE THERAPY:
- Twin technology
- Focus on regenrationg cochlear hair cells which are fuctioning by reversing the genetic defect as well