3rd November 2020

The collaboration with Evox on exosomes has been completed early. We have successfully demonstrated mRNA loading but optimising this process requires further work by Evox alone.

In September 2018, Duchenne UK funded Evox Therapeutics with a grant of £655,000 to investigate using exosomes, a potential alternative to using viruses, to deliver gene therapy.

Exosomes are nanoparticles that all cells release, and which contain proteins and other large molecules. They are the body’s natural way of effectively, safely, and repeatedly delivering molecules from cell to cell, and even crossing the blood brain barrier to access the brain.

The aim of this project was to see if exosomes could be used to deliver gene therapy to muscle cells.

Several companies are now testing gene therapy in DMD, by using viruses to deliver the micro-dystrophin. However, many people with DMD may have pre-existing antibodies to the viruses being used to deliver gene therapy, which makes them ineligible for this treatment. Similarly, patients receiving viral gene therapy would develop immunity making repeated dosing, if required, impossible. This is why we collaborated with Evox – to look at ways of making gene therapy available to all patients.

During the course of this collaboration, Evox has been able to load mini- and micro-dystrophin mRNA into exosomes (for technical reasons full-length dystrophin was not available for testing).

Evox has decided to carry out further optimisation of its mRNA loading approach work itself (and at its own cost) before then directing it towards the treatment of a variety of muscular skeletal diseases, including potentially DMD.

As a consequence, Duchenne UK has completed its work with Evox early.

We carefully fund projects in staged payments, so the remaining funds for this project will be re-distributed.

Q&A with our Director of Research, Dr David Bull

Why can’t we continue to use viruses to deliver gene therapy, rather than exosomes?

Well, we can – but there are problems. The main one is that our bodies have evolved to protect us from invading viruses and bacteria. We call this ‘immunity’ or the ‘immune response.’ Putting a dystrophin gene (or part of one) inside a virus is a great way of getting it into muscle cells but as soon as we give this to our boys we hit two problems: First, the patient may already have developed an immunity to the virus – picked up naturally from the environment. Our bodies will see this and mount a defence – they will also remember the virus and be ready for the next time. Up to 30 or 40% of boys may have this natural defence. Secondly, if we give the gene therapy to someone who has not seen the virus before then it will get to where it is needed. But the body will remember this for the next time and be ready – a second administration of the viral therapy will not work.

We think there may be better ways to deliver gene therapy – so, exosomes.

What are exosomes?

Think of them as minute transport containers. They are only about 1/100,000th of a cm across but they very important for cell to cell communication. They are packed with a cargo of lipids, proteins and nucleic acids and can access all cells in your body – they even get into the brain.

Critically, the body sees nothing unnatural about exosomes – no need to mount a defence. Indeed, if you have ever had a blood transfusion you have received many millions of someone else’s exosomes with no adverse effect. 

Why were they being investigated as a treatment for Duchenne?

It’s possible to make artificial exosomes and then to fill them with a desired ‘treatment’ – in our case genetic mRNA with instructions for dystrophin (or a shortened form). It is also possible to modify the exosome coating with proteins that instil a preference for them to enter muscle. So – these exosomes have the potential to be used to deliver a new copy of the dystrophin gene to Duchenne boys in the same way that we are doing with viruses but without the immune issues associated with viral therapy.

Duchenne UK would like to thank our partner charities for their contribution to this project: Alex’s Wish, Caring for Connor, Chasing Connors Cure, Duchenne Now, Hope for Gabriel and Joining Jack 

We would like to also thank our family funds for supporting the project: Archie’s March, Help Harry, Hope for Harry, Jack’s Mission, Jacobi’s Wish, Lifting Louis, Project GO, Smile With Shiv, Team Dex, Team Felix and William's Fund.

NOTES FOR EDITORS

What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no treatment or cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease.

Who are Duchenne UK?

Duchenne UK has one clear aim – to end Duchenne, a devastating muscle-wasting disease. As the leading Duchenne charity in the UK, we connect the best researchers with industry, the NHS and families to challenge every stage of drug development to make the incurable, curable. Together, we will find treatments and cures for this generation of patients with Duchenne.

Our president is HRH The Duchess of Cornwall. Our patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell. 

We need your help, because we need to keep funding promising new research.

How to donate?

Duchenne UK is entirely reliant on donations to fund research for treatments and a cure to DMD. 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.

For more information visit www.duchenneuk.org