Life without the ability to hear is really tough to imagine. What if we never hear the sound of such good music , water flowing , sound of rain , sound of ocean waves , voices of our loved ones and many more, yes it is difficult.
According to the data , around 1.7 per 1000 babies in united states are born with congenital deafness and most of the cases are due to genetic deficiency.
Recently OTARMENI (first and only gene therapy for genetic hearing loss ) has been approved by FDA for severe to profound deficiency in children that have mutant OTOF gene. OTOF gene is responsible for synthesizing a protein called otoferlin , that is required for transmission of nerve signal to auditory nerve by releasing a neurotransmisttor , without it the signal never reaches the brain so there is no recognition response.
Now how this therapy works ? so this OTARMENI is a Adeno-Associated Virus (AAV) Vector used for delivering the OTOF gene to the inner sensory hair cells. A surgical procedure is performed to deliver this drug in the inner ear. Where this vector travels to the inner hair cells and floats in the nucleus of inner hair cell as a Episome.
The question arises why a virus is used here ? because as we know viruses are very excellent at invading the membrane and entering the living cell. So this virus is modified to prevent its virulence nature and use its ability to deliver the therapy product at the target site , without the need to develop a special microscopic delivery mechanism or a vector , this is known to be the " Trojan Horse Strategy ".
This drug is developed by Regeneron , a trial was conducted named CHORD trial where initially 12 participants were included for the testing of this drug. Out of 12 , 9 patients achieved the primary hearing target as well as there were improvement in speech perception and development.
This trial will continue and still recruiting and aim to assess outcomes for 5 years after OTARMENI treatment.
Details of the trial can be accesses from this link :
https://www.nejm.org/doi/full/10.1056/NEJMoa2400521
The anatomy of the ear is intact , its just at the genetic level lies the problem that is causing hearing loss, so this therapy only works if the inner hair cells are intact. So this is not useful in healing loss due to other factors atleast till now , because hearing loss can be due to reasons such as drug induced ototoxicity , accidental deafness ,etc .
Can you tell some other gene therapy where a virus is used as a vector ?
Can you name some drugs that causes Ototoxicity and what is the mechanism and why it can’t be reversed by such gene therapy?
