Overcoming immunity challenges in gene therapy

Joining Jack has contributed £185,000 to a £1/2million Duchenne UK grant to overcome immunity challenges in gene therapy

The aim of this project is to give every DMD patient access to gene therapy

We have partnered with one of the world’s leading gene therapy teams focusing on AAV immunology, Drs. Manuela Corti and Barry Byrne at the Powell Gene Therapy Center, University of Florida to try to temporarily modify the immune system so that anybody can be treated with gene therapy, and, if necessary, can receive repeat doses.

There are currently several gene therapy programmes in the clinic, which all use a virus to try to replace the faulty dystrophin gene. The early data looks promising.

But there are challenges around immunity to the virus used to deliver the gene therapy, that we need to overcome to get this treatment to the entire DMD population,

Challenge 1: Natural immunity

Many people with DMD already have a natural immunity (sometimes described as pre-existing antibodies) to the virus, so their immune system would fight the virus and it would not be able to deliver the replacement gene therapy.

Challenge 2: Repeat dosing

People without natural immunity who can get one dose of gene therapy will develop immunity after their first dosing, so they cannot have more than one treatment.

We are funding this project to find solutions to BOTH the immunity issues.

Drs. Byrne and Corti are developing a newly designed piece of genetic code, to be delivered by the AAV virus. This will be tested in mdx mice using different regimes of immunosuppression devised by the Powell Gene Therapy Center team.

Our main goal is to identify the best strategy to modify the immune systems so that patients can receive gene therapy - both those with pre-existing immunity and those who require repeat dosing.

This is the first stage of a larger development approach. If the team is successful in this first phase, they will go on to test the best code and the best immunosuppression regimen in other DMD animal models more closely related to the human condition.

Drs. Manuela Corti and Barry Byrne at the Powell Gene Therapy Center, University of Florida, said

We are excited to collaborate with Duchenne UK and to take the next step in fulfilling our commitment to patients and families living with DMD. This project is an important milestone in the development of a successful gene therapy treatment that could dramatically improve the quality of life for patients with DMD of all ages to ensure durability and safety.

Alex Johnson, co-founder of Joining Jack, said:

We are committed to helping where it can to advance the development of gene therapy to and ensure that this promising treatment will be available for all patients regardless of the challenge of antibodies. We are very pleased to be announcing this project and are very grateful to our supporters in helping to fund this.

To find out more about this project, please join our webinar this Wednesday 8th July at 6pm. Co-founders of Duchenne UK, Alex Johnson and Emily Crossley, will be joined by Duchenne UK’s Director of Research Dr. David Bull and Drs. Manuela Corti and Barry Byrne to discuss gene therapy and this new project.

We would like to thank Duchenne Now and Jacobi’s Wish for generously supporting this project.

We would also like to thank the following partner charities and family funds: Project Go, Cure4George, Smile with Shiv, Team Felix, Following Felix, Team Oscar, Defending William Against Duchenne, Jack's Mission, Chasing Connor's Cure, Help Harry, Action for Arvin, Backing Jack, William's Fund.