Technology used in COVID-19 vaccine to be used for Duchenne muscular dystrophy gene therapy research 5 May 2021 Duchenne UK has invested £287,500 into a new 18-month study investigating whether Lipid Nanoparticles (LNPs) could be used to help in gene therapy treatments for DMD. Lipids are naturally occurring small fatty molecules that exist within the body, and nanoparticles refers to their small size. LNPs are currently being used as a key component in the Pfizer/BioNTech and Moderna COVID-19 vaccine. Duchenne UK is now funding work to see whether these LNPs could be used to deliver gene therapy in DMD. Several clinical trials of gene therapy are now underway in DMD using harmless viruses, called AAVs, to deliver synthetic gene to replace the faulty dystrophin gene in Duchenne. The early data looks 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. There are also difficulties in transferring the genes from the viruses into muscle cells. This study aims to address some of these challenges by exploring LNPs as a method of delivering gene therapy. The study is called ‘mRNA Targeted Therapeutics for Duchenne Muscular Dystrophy’ and will be led by Professor Shenhav Cohen at Technion Institute of Technology, Israel, in partnership with Professor Aartsma-Rus at Leiden University Medical Center and Professor Peer at Tel Aviv University. LNPs can be filled with a variety of materials, including genetic material. Because LNPs are made of naturally occurring lipids, they should not cause an immune response. They also have a good safety profile for use in humans. This study will explore whether a larger dystrophin construct can be carried by the LNPs. The dystrophin gene is the largest gene in the body, but in current gene therapy trials, a shortened construct must be used. Our current understanding of the impact of shortened dystrophin on long-term muscle function is limited, but using a longer gene could lead to better muscle function. The research group plans to engineer the LNP surface such that the LNP will effectively fuse with muscle and deliver its cargo. This research is currently in very early stages. If the researchers can show that this method can effectively deliver genetic material into muscles using a mouse model of DMD, they would have a high chance of receiving a much larger grant for further research. We are excited to be funding this early research into a safer and more effective way to deliver gene therapy, alongside other projects looking to reduce the immunological issues of using viruses. If successful, this project could have a transformative impact on the way gene therapy is delivered for DMD in future. We would like to thank our charity partners, Alex's Wish and Little Steps, and the following Family Funds for contributing to this project: Chasing Connor’s Cure, Jack’s Mission, Help Harry, Archie’s March, Muscles for Mitchell, Jacobi’s Wish, William’s Fund, Project Go, Action for Arvin, Following Felix, Defending William Against DMD, Henry’s Hurdles; Ben vs Duchenne. Q&A Why are immune responses a problem when delivering gene therapy? An immune response is how your body recognises and defends itself against potential harm, such as viruses. Currently, gene therapy is being trialled using viruses called AAVs (adeno-associated viruses). However, if an individual has come into contact with the virus before, they will have already developed antibodies which will detect and attack the virus as soon as it enters the body. This means that the genetic material cannot reach the cells. This is the case for a significant percentage of patients. In addition, once a dose has been given to a patient, they will develop an immunity. There will then be little to no chance of further dosing, should it be required. For more information on the challenges of gene therapy, watch our video here. How will LNPs be engineered to facilitate gene therapy? We know that using AAVs to deliver new genetic material is inefficient – we need to give far more virus than we would wish to. The LNPs will be linked to a molecule that can bind muscle cells more effectively, and therefore improve the transfer of the genetic material into the cell. What’s the difference between LNPs and Exosomes? Exosomes are naturally occurring, but they are smaller, and there have been difficulties around getting a large enough construct into them. LNPs, on the other hand, are manufactured and can be built to a larger size to allow a larger amount of genetic material to be inserted. You can read more about our work with Evox Therapeutics on exosomes here. If this project is successful, when could it lead to treatments being developed? This research is currently in very early stages, and as with all research, there is no guarantee of success. If this study can prove that LNPs are effective in an animal model of DMD, further research would then be needed to prepare this delivery method for clinical trials. A potential clinical trial could then start within five to six years. NOTES FOR EDITORS About Duchenne UK Duchenne Muscular Dystrophy (DMD) is a devastating muscle-wasting disease. It is the most common and severe form of Muscular Dystrophy. Diagnosed in childhood, it mainly affects boys. There is currently no cure. Started by families affected by the disease, Duchenne UK has one clear aim – to end Duchenne. Duchenne UK are funding research that’s focused on getting treatments to those affected now – as well as pushing for an effective treatment in the future. Duchenne UK connects leading researchers with industry, the NHS and patients to challenge every stage of drug development, from research to clinical trials to drug approval. They connect families with each other to create a network of mutual support and to pool resources, knowledge and experience. How to donate COVID-19 has caused a funding crisis in medical research. But we cannot, and will not, let it slow us down in our mission to find new and effective treatments for DMD. Because this generation of boys cannot wait. Donate now, and together we will end Duchenne Duchenne UK is entirely reliant on donations. This can be done via: Direct Debit – Duchenne Direct Individual Donation – Donate If you are a family or friend affected by DMD you can set up your own fund with Duchenne UK – Family and Friend Funds Take part in one of our fundraising events – Events Text DUCHENNE to 70085 to donate £5. This costs £5 plus a std rate msg.