Alex’s Wish grants £60,000 to Evox TherapeuticsNovember 19, 2018 9:15 pm
This is an exciting time for research into Duchenne Muscular Dystrophy (DMD). Several companies are now testing an approach that uses a synthetic gene to replace the faulty dystrophin gene in Duchenne. This is known as gene transfer using micro-dystrophin. Or more commonly, gene therapy. The companies are using viruses to deliver the therapy.
The early data looks very promising. But there are some challenges in getting this treatment to the entire DMD population, mainly because some patients will have pre-existing antibodies to the virus’ and so will not currently be able to have the treatment.
This is why Alex’s Wish has granted £60,000 with Duchenne UK to fund £655,000 to a pre-clinical DMD program with Evox Therapeutics, a company looking at using exosomes to deliver the gene without using a virus.
Exosomes are small nanometer-sized vesicles that occur naturally in cells and carry out different functions. They are essentially small sacs of membrane which carry nucleic acids and proteins. Nucleic acids are large molecules where genetic information is stored, such as DNA and RNA. Think of exosomes like little parcels which deliver information around the body.
The question we are trying to answer is ‘can exosomes be altered to deliver dystrophin mRNA or its shorter variants (often known as micro-dystrophin) to muscle cells?’. If the answer is yes, then exosomes could provide a potential new method for effectively, safely, and repeatedly delivering mRNA for dystrophin to muscles. Crucially, exosomes are far less likely to cause an immune response meaning pre-existing immunity or administration-acquired immunity should potentially be much less of an issue (see below).
The Evox team includes Professor Matthew Wood (University of Oxford), who has a wealth of experience in DMD treatment approaches and who we have worked with before exploring other treatment approaches.
Evox is engineering exosomes, the body’s natural vesicular delivery system, to enable a wide variety of drugs to reach previously inaccessible tissues and compartments, such as crossing the blood brain barrier to deliver drugs to the central nervous system, intracellular delivery of proteins, and extra-hepatic delivery of RNA therapeutics. Evox is developing its own proprietary pipeline of exosome-based therapeutics for the treatment of rare, life-threatening diseases with significant unmet need.
Part of Duchenne UK’s mission is to make sure we find and fund projects that cover all areas of research that demonstrate a potential to treat and cure DMD. We want to leave no stone unturned!
We are really excited to be supporting a project investigating a new potential method of gene therapy delivery. If successful, then we are nearer our ultimate aim of all DMD patients producing their own dystrophin
There are, however, some challenges at present in using Gene therapy as a potential treatment for DMD.
The dystrophin gene is the largest human gene and currently, it is not practical to insert the entire dystrophin gene mRNA into an Adeno-associated virus (AAV) vector (which is the method used by many of the gene therapy trials currently taking place).
As mentioned above, another challenge concerns issues with immunity. When using AAV viral vector delivery, some patients will already have a natural immunity to the virus, so their immune system would fight the virus such that it could not deliver its replacement gene therapy. In addition, all patients receiving the viral vector will develop immunity after the first dosing, so they cannot have more than one treatment. This may be a problem as the effect of the first treatment will be diluted with time and patients will require re-administration.
This project with Evox will look at whether it is possible to deliver the dystrophin gene mRNA or its shorter variants using exosomes, as an alternative delivery method to viral vectors.
This investment is a fabulous demonstration of how the Duchenne Community is working together.
Along with Duchenne UK and Alex’s Wish £60,000 the investment has come from Caring for Connor (£5,000), Chasing Connors Cure (£20,000), Duchenne Now (£100,000), Hope for Gabriel (£5,000) and Joining Jack (£200,000) Archie’s March (£5,000), Help Harry (£14,000), Hope for Harry (£10,000), Jack’s Mission (£20,000), Jacobi’s Wish (£15,000), Lifting Louis (£20,000), Project GO (£20,000), Smile With Shiv (£10,000, Team Dex (£10,000), Team Felix (£60,000) and William’s Fund (£40,000).
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