Gene therapy is arguably one of the most difficult drug strategies in play today. How researchers are using common viruses to shuttle genes to cells 

The French-based AFM-Téléthon and US-based Odylia Therapeutics  work on very different diseases, but what they have in common is that the diseases are both rare, genetic disorders. AFM-Téléthon supports the development of innovative therapies to combat neuromuscular diseases, including Duchenne muscular dystrophy, and Odylia’s mission is to find treatments for rare retinal disorders.  

Gene therapies hold a lot of promise in regressing and even curing diseases. They are also arguably one of the most difficult drug strategies in play today. After decades of trying, only a handful of gene therapies have made it to market.

For the neuromuscular disease that AFM-Téléthon targets, the challenges begin with the fact that the disease affects half the body weight—all the muscles and sometimes the spinal cord and brain. This means that systemic administration of the gene therapy is necessary for a treatment to be effective. Finding the right viral vectors that are efficient and robust enough to do this has been a huge hurdle for researchers, says Serge Braun, scientific director of the AFM-Téléthon.

Odylia is developing gene therapy treatments for Usher syndrome, an autosomal recessive disease that causes profound deafness at birth, vestibular dysfunction and degenerative sight loss in early adolescence ultimately leading to blindness. They are developing adeno-associated viral (AAV) vectors that deliver the gene therapy to the retinal space, to try and restore or preserve vision in people with Usher’s.  Harrison Brown, the chief scientific officer at Odylia, said because the eye is an immune-privileged space, it remains protected from the immune responses that the viral vectors used in gene therapies can provoke when the drug is delivered systemically.

“That being said, there are several issues that we still face with some retinal gene therapies, including the difficulty of transducing the proper tissue,” said Brown. While Odylia has licensed an AAV vector with a serotype that has strong affinity and tropism, which is allowing them to transduce the proper tissue in the eye, they are also facing the challenges of delivering the therapy surgically. “It’s a very specialized surgery known as subretinal injection, where you can actually inject it through the sub-retinal space,” says Brown. “This is a great target tissue to go to because the main tissues that are affected by these genetic diseases are the photoreceptor and the RPE itself. However, there aren’t very many surgeons who are skilled in this technique yet, and so that poses several obstacles.”

Both Braun and Brown were part of a roundtable discussion on gene therapy moderated by David Fischer, Executive Director of Discovery Sciences at Charles River. The discussion was taped at the Charles River Second World Congress Meeting held last month.

You can watch the entire discussion by clicking on the link above.