One million dollars (US$) are committed to fund the best research proposal/s which support enhancing gene therapy delivery for the treatment of Duchenne Muscular Dystrophy

Duchenne UK (DUK), a UK-based patient organisation, and Parent Project Muscular Dystrophy (PPMD), a USA-based patient organisation, are pleased to announce the launch of their joint 2020 Research Grant Call and wish to invite research proposals for submission and review.

Specifically, and solely, we are interested in receiving proposals relating to:

Minimising the immunological issues of gene therapy in the treatment of Duchenne Muscular Dystrophy

It is likely (but not certain) that funding will be awarded to a single project.

Why have we chosen to focus on this area?

Over the last few years we have seen huge progress in the treatment of the root cause of Duchenne muscular dystrophy through the delivery of replacement (micro) dystrophin using gene therapy. The delivery to muscle of the genetic material for these microdystrophins has been achieved through the use of viral capsids, predominantly AAV-derived. Although we are still in the early stages of this research, we do have evidence that we can detect the presence of microdystrophin protein in treated boys. However, there are some major drawbacks relating to the immune responses to such delivery vehicles. A significant number of boys have a pre-existing resistance to the capsids (and so are ineligible for treatment), but even those that have no such innate resistance will develop it after the first administration, making second dosing (if required) very difficult.

More is needed to advance our understanding of the best ways we can safely, effectively and repeatedly deliver gene therapies to the muscles where they are needed.

What sort of projects are we looking to fund?

Primarily we are inviting proposals which are investigating ways to mitigate the immune response both in terms of pre-existing resistance and resistance induced by receiving a gene therapy dose. These may focus on the ‘damping down’ or ‘circumventing’ the immune system itself or may be investigating alternative delivery methods that promote a minimal immune response. It is important to note that if the latter is the focus of a proposal, we will only consider methods that can deliver full-length dystrophin constructs or enable robust transfection of satellite cells.

In addition, this call has a relatively narrow remit in terms of the development stage. Submissions ready for, or in, early clinical trials will be favoured although we will consider proposals that are in late preclinical stage which show great promise.

Who can apply?

Proposals may be submitted from academic groups or from small commercial concerns. In either case, contracting discussions will include shared ROI.

How to submit your proposal?

In the first instance send an email, including a brief (2-3 page) outline of the project and approximate costs using the template (download template here). If your proposed project is accepted for further consideration, we will send you a detailed submission template which you should complete in full and return.

Please send to this address:

[email protected]

Submissions, sent as above, should be received by 21st July 2020 at the latest

How will your submissions be reviewed?

All submissions will be carefully reviewed, initially by our joint Science Review team and by the CEOs from DUK and PPMD. Subsequently there will be a thorough review of proposals by a specially convened Scientific Advisory Board. You will, of course, be advised of the progress of your submission at all stages.

PPMD’s Founding President & CEO, Pat Furlong, and Duchenne UK’s CEO, Emily Crossley explained in a joint statement:

Supporting patients and accelerating innovative research is at the heart of what we do at Duchenne UK and PPMD. We are pleased to partner with each other and offer this grant of US$1million. Gene therapy is offering great promise, but there are challenges associated with the immune response which are limiting the rate of progress and a barrier to ensuring all patients can have access to these potentially transformative therapies. We hope that this call will encourage groups working in this area to submit applications and engage with us in bringing new treatments to the clinic.

The Directors of Research at DUK and PPMD, said:

We know that research groups around the world are doing varied and exciting work aimed at defeating this disease. By partnering together to identify and support these cutting-edge projects DUK and PPMD seek to accelerate the timeline of translation to patients in need of these exciting therapies.

Notes for editors:

Previous Grant Calls

Both PPMD and Duchenne UK have launched and managed successful grant calls previously. Below are the most recent:

In 2019, Duchenne UK launched a Grant call for £2 million. The successful recipients were:

  • Dr Rita Perlingeiro - Preclinical Studies in Pluripotent Stem Cell-Derived Myogenic Progenitors to Enable a First in Human Phase 1 Safety/Dose Escalation Trial for Duchenne Muscular Dystrophy
  • Dr Ingrid Verhaart - Effect of nicotinamide riboside on DMD: preclinical studies in DMD mouse models
  • Dr Olivier Dorchies - Novel approaches designed to regenerate muscle fibres and/or remove/reduce fibrosis in muscles
  • Dr Kitipong Uaesoontrachoon - Repurposing FDA Approved JAK inhibitors (Tofacitinib and Ruxolitinib) as the treatment option for DM

In 2019, PPMD placed a Request for Application for $500,000 to develop therapies aimed at cardiac dysfunction in Duchenne. The successful recipient of that RFA was Dr. Renzhi Han, at The Ohio State University. Dr. Han’s work utilizes a CRISPR platform to correct mutations in the DMD gene without inducing double stranded breaks. Dr. Han is investigating restoring full length dystrophin production through gene editing in an exciting new model that more accurately mimics cardiac disease progression in DMD.

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 currently no treatment or cure. There are around 300, 000 patients affected worldwide. It is classified as a rare disease.

Who are Duchenne UK and PPMD?

Duchenne UK has one clear aim – to end Duchenne. We are the largest funder of Duchenne research in the UK. We connect leading researchers with industry, governing bodies and families to challenge every stage of drug development. Together, we will find treatments and a cure for this generation of patients with Duchenne.

Parent Project Muscular Dystrophy (PPMD) is the largest most comprehensive non-profit organization in the United States focused on finding a cure for Duchenne—our mission is to end Duchenne. We demand optimal care standards and strive to ensure every family has access to expert healthcare providers, cutting edge treatments, and a community of support. We invest deeply in treatments for this generation of Duchenne patients and in research that will benefit future generations. Our advocacy efforts have secured hundreds of millions of dollars in funding and won three FDA approvals. Everything we do—and everything we have done since our founding in 1994—helps those with Duchenne live longer, stronger lives. We will not rest until we end Duchenne for every single person affected by the disease.

For more information about Duchenne UK: visit www.duchenneuk.org or email Molly Hunt – Communications Manager, Duchenne UK at [email protected].

For more information about PPMD: visit www.parentprojectmd.org or email Will Nolan – SVP of Communications, PPMD at [email protected].