Hearing loss and gene therapy

Hearing loss and gene therapy

लोग कितने प्रभावित हैं 

 it is estimated that over one billion people suffer from hearing loss and approximately one-two children in every 1,000 births are born with congenital hearing loss.

क्या कारण हो सकता  है ?

१  Hearing loss is a complex condition that can result from a variety of environmental and genetic factors including ear infections.

 २ Often, hearing loss serves as symptoms indicating defects or pathologies in the ear’s process that converts sound into electrical signals sent to the brain.

जेनेटिक कारण 

 1 It is widely estimated that a significant majority, amounting to approximately 50-60% of congenital hearing loss cases, are attributed to genetic causes. 

2 GJB2 gene

For example, mutations in the GJB2 gene are the most common genetic cause of hearing loss in Caucasian, Asian and Hispanic populations. 

3 In Africa, the MYO15A and ATP6V1B1 genes are more frequently implicated.

4 In total, over two dozen genes have 

been linked to genetic causes of hearing loss. 

Besides genomic mutations, mitochondrial genetic defects 

can also lead to hearing impairment. 

Genetic variants could also play a role in the complex interplay with other factors, like medications. 

For instance, a prevalent genetic defect in the mitochondrial MTRNR1 gene can predispose individuals to hearing loss when administered with the aminoglycoside antibiotics, widely used in treatment of TB.

Emerging therapies

gene therapy and genome editing

Correction of the gene defect underlies the genetic cause of hearing loss, and therefore gene therapy and genome editing have been touted as one of the possible emerging therapies. 

Gene therapy typically involves 

1 replacing or supplementing a dysfunctional gene with normal or functional genes

2 Adeno-associated virus (AAV) 

is one of the most well-studied and widely used vectors for this purpose. 

AAV offers several advantages: it is a safe vector, as it does not cause human diseases, and it can infect both dividing and non-dividing cells, thus having a broad spectrum of cells it can target for genetic editing.

. Researchers at the Fudan University

in collaboration with a number of research and clinical centres in China, proposed that gene therapy could effectively treat a form of genetic deafness involving the OTOF gene, known as hereditary deafness 9.

 Mutations in the OTOF gene account for approximately 2-8% of all genetic hearing loss cases. 

In this clinical trial, researchers employed Adeno-associated virus vectors with the intention of inserting a healthy OTOF gene into patients’ ears using a harmless virus. .

36-odd minor side effects

As 

• increased lymphocyte counts 
• and cholesterol levels apart from 
• an increase in lactate dehydrogenase levels, which is a marker for tissue damage in the body.

Set of caveats

Adeno-associated virus vectors 

While the initial results are encouraging, Adeno-associated virus vectors come with their own set of caveats. 

The foremost being that our immune system can recognise and eliminate the virus making it less effective in individuals who are immunised, 

and also limits the re-administration of the gene therapy vector, since the primary administration would produce antibodies against the virus.

 Previous studies have suggested that approximately one-fifth to one-third of the patients have neutralising antibodies against AAV.

Source the hindu