Duchenne UK announced that it has awarded a sizable grant to Evox Therapeutics to advance in early testing a way of using gene therapy to deliver — without a virus as a transport agent — the dystrophin gene or shorter versions of it to people with Duchenne muscular dystrophy.
The group’s £655,000 (about $864,000) award will be used by the company to explore exosomes — natural vesicles that carry information between cells — as a way of delivering dystrophin to muscle cells.
Most research underway into gene therapies uses harmless viruses to carry the treatment, called a viral vector, and patients with antibodies to those viruses cannot be treated.
“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,” Duchenne UK , a charitable organization that advocates for and supports research into DMD treatments, said in its press release.
“We are excited to be working with Duchenne UK on exploring a potential transformative solution to treat Duchenne patients,” said Antonin de Fougerolles, PhD, chief executive officer of Evox.
In DMD patients, the production of dystrophin is defective. This protein is essential for muscle development and its proper functioning. Lack of dystrophin results in weakening and eventual damage of the muscles, including the heart muscle.
Gene therapy has shown promise in increasing dystrophin levels by replacing the defective dystrophin gene with a synthetic functional one. But its use may be limited if it relies on genetically engineered viruses for delivery.
“One of the most challenging aspects of using viruses to deliver gene therapy is that many patients may already have what are known as pre-existing antibodies — they are ‘resistant’ to the virus — and so the replacement gene carried by the virus will never reach its target,” Emily Crossley and Alex Johnson, co-CEOs of Duchenne UK, said in a release on the group’s website.
Others may also have an immune reaction, should their systems perceive the virus delivering the treatment as foreign. And all patients can develop immunity after one treatment, meaning they cannot be treated again — and an initial treatment might not be sufficient for DMD patients, the group said in its release.
Evox is developing a gene therapy delivery system using exosomes instead of viruses. Exosomes are the body’s natural packaging system, i.e., they are small packets that carry information — such as DNA, RNA and protein — throughout the body, and into areas that are often inaccessible, including the central nervous system. Company scientists are attempting to modify exosomes in ways that would enable them to bring dystrophin (dystrophin mRNA) to muscle cells.
“Exosomes could provide a potential new method for effectively, safely, and repeatedly delivering genetic material encoding for dystrophin to muscles without the problem of pre-existing antibodies,” Crossley and Johnson said.
Since exosomes are naturally occurring in the body, researchers think that those modified to carry dystrophin mRNA may not be considered foreign, and patients won’t have reactions or develop resistance to them.
The dystrophin gene is the largest known human gene, and dystrophin mRNA also tends to be large. Researchers have found it difficult to pack this large molecule in virus-based delivery systems. Anticipating similar issues, Evox will focus on redesigning exosomes so that muscles cells can at least receive a functional, if shorter, form dystrophin mRNA.
“We will conduct research to assess the potential of our exosome drug platform to deliver functional dystrophin which is missing or defective in these patients,” de Fougerolles said. “This work will also allow us to explore targeted delivery of exosomes to muscle which may be beneficial not only for Duchenne patients, but also ultimately for patients with other musculoskeletal diseases.”