Our mission is to bring about new treatments to help delay the onset of symptoms in boys with Duchenne and ultimately find that cure! We hope to eradicate Duchenne for all in the next 5-10 years. The funds received through Alex’s Wish are directed in full to Duchenne Muscular Dystrophy research and clinical trials. We also collaborate with other non-profit organisations which have similar goals to Alex’s Wish concerning current and promising advances being made in Duchenne Research.
We have funded a number of exciting new projects including early-stage research, drug development and clinical research infrastructure.
Summary of projects funded
Early stage research:
Gene Therapy (Solid-GT)
Alex’s Wish partners with Solid-GT and funds important Gene Therapy Development
We would like to thank all of our supporters who have enabled us to give a £50,000.00 grant to Solid-GT to support their Gene Therapy Development.
“Solid is proud to establish meaningful and impactful relationships with DMD charities to accelerate the progress of as many of our programs as possible,” said Kerry Rosenfeld, lead of Solid Patient Advocacy in Europe. “We believe this work will bring us closer to finding effective treatments for this devastating disease.”
Gene therapy is a therapeutic approach that aims to significantly slow or even halt the progression of Duchenne muscular dystrophy by delivering the dystrophin protein throughout the body.
Solid Biosciences chose to form Solid GT and focus initial efforts on gene therapy due to the significant progress in our understanding of the dystrophin gene, recently reported successes in gene therapy clinical development and advances in gene therapy manufacturing.
Facts Important For Gene Therapy Development
Solid GT’s lead program is an adeno-associated virus (AAV) micro-dystrophin gene therapy candidate, which aims to enable the systemic delivery of a shortened yet functional version of the dystrophin gene to the body. In addition, we are actively exploring other potential gene therapy candidates that could be beneficial for Duchenne muscular dystrophy.
The vehicles that enable widespread delivery of these genes to the body are small viruses, derived from adeno-associated viruses or AAV. These viruses are not known to cause diseases and are currently being explored for the delivery of therapeutic genes for many genetic disorders. However, the gene carrying capacity of the viruses is too small to carry the entire dystrophin gene.
Over the past two decades, design improvements to minimize the size of the dystrophin gene have resulted in micro-dystrophin genes that are believed to retain the most critical components of the larger version yet are small enough for the AAV to carry.
Solid chose to pursue gene delivery of micro-dystrophin because this approach has the potential to restore widespread functional dystrophin expression regardless of a patient’s specific mutation. Results from two preclinical studies have demonstrated that a single administration of the AAV-micro-dystrophin vector led to significant expression of the micro-dystrophin protein in skeletal and cardiac muscles, as well as improvements in muscle histology and function.
Currently, Solid GT is conducting a number of key studies that are intended to enable us to enter the clinic in 2017. Solid GT is performing this research in collaboration with the University of Missouri, the University of Washington, the University of Florida and Texas A&M University.
For more information please visit Solid GT’s website
Alex’s Wish has proudly funded seven new research grants in collaboration called the Duchenne Alliance with a number of UK based charities: The Muscular Dystrophy UK, Joining Jack, The Duchenne Research Fund, and Harrison’s Fund – together we have committed £840k over 4 years (2013-2016). Click on the links for more details.
- Professor Dame Kay Davies, University of Oxford – Increasing Dystrophin
- Professor George Dickson, Royal Holloway University, London – Gene Therapy
- Professor George Dickson, Royal Holloway University, London – Genome Surgery
- Professor Jennifer Morgan, University College, London – Stem Cells
- Dr Angela Russell, University of Oxford – Increasing Utrophin
- Professor Mathew Wood, University of Oxford – Discovering Biomarkers
- Professor David Abbott, University of Bristol – End of Life Care
Each of these grants will move us closer to finding treatments for Duchenne Muscular Dystrophy
Repurposed Cancer Therapeutics
Drug repurposing takes existing generic drugs licensed for human use, and tries to find other illnesses that they could treat. It is faster and less expensive than normal drug discovery, because we already understand the drug’s behaviour and side effects in humans; we already know about dosing and delivery of the drug; and we understand the drug’s mode of action. It is therefore an excellent option for rare diseases, where there is a lack of research funding and few available treatments.
Alex’s Wish has helped co-fund this repurposed project alongside Action Duchenne, Duchenne Now and Harrison’s Fund, the project will be led by Professor Steve Winder in the Department of Biomedical Science at the University of Sheffield. With a total cost of £120,935, this project hits the strategic aims of each of the funding charities by showing the potential to treat all Duchenne patients and the possibility of a fast-track to the clinic.
The project will investigate the use of four drugs that are currently used to treat cancer as potential treatments for Duchenne, using mouse models. The project aims to assess:
- the long-term efficacy of three tyrosine kinase inhibitors in reducing the dystrophic patho-physiology in mdx mice.
- the long-term efficacy of a proteasome inhibitor in reducing the dystrophic patho-physiology in mdx mice.
- the possible synergistic effect of tyrosine inhibitors combined with proteasome inhibitors in further reducing the dystrophic patho-physiology in mdx mice.
In people living with Duchenne Muscular Dystrophy, a faulty signal in the cell acts as a switch which leads to disruption of the muscle cell surface. This ‘faulty switch’ is part of the cause of Duchenne. If this ‘faulty switch’ could be turned off it could stop or reduce the muscle damage associated with DMD. Some cancers are caused by the same kind of faulty switch, and therefore the same drugs that are used to treat these cancers may also have therapeutic benefit in Duchenne.
The team behind this project have previously experimented with these drugs in zebrafish models that have Duchenne, where they worked as expected. They have also used two of the compounds on mdx mice, with encouraging results. The next step is to use all four compounds individually and in combination in mouse models, over a longer period of time. If successful this project will be a crucial step in gaining approval for a clinical trial of these treatments in human subjects. Because the drugs used in this project are already approved for cancer patients they could potentially be fast tracked to the clinic for Duchenne patients if this research project is successful. We will keep the Duchenne community updated with the progress of this novel and exciting project.
Alex’s Wish co-funded a research project into Quercetin, a flavonoid with an outstanding safety profile, which may provide therapeutic relief to Duchenne patients as the wait for additional therapies continues. This study evaluated the capacity of orally administered quercetin in mice to improve respiratory function. Respiratory function was protected for the first 4–6 months of treatment but appeared to become insensitive to Quercetin thereafter. A continued study is needed to determine if this is related to disease severity, age or other factors.
HT-100 – A powerful Anti-Inflammatory and Anti-Fibrotic
We are supporters of this very exciting clinical trial which is being run by Akashi Therapeutics. Many other UK Duchenne charities have invested too into this promising new treatment which will hopefully help all boys with Duchenne, regardless of their mutation type.
In non clinical studies (animal studies), HT-100 an oral drug, has been shown to decrease fibrosis, decrease inflammation and muscle degeneration, increase muscle regeneration and improve motor, pulmonary and cardiac function. Akashi Therapeutics has been running clinical trials in boys with Duchenne Muscular Dystrophy.
During recent clinical trials in boys with Duchenne, a patient died and further investigations are now taking place to understand why and how this patient died and whether it was in part due to the trial he was taking part in. We are awaiting further details. For more information, please visit their website.
VBP15 – a novel steriod drug for Duchenne
In 2015, Alex’s Wish awarded a £50k grant to help progress clinical trials of an oral drug called VBP15, developed by ReveraGen BioPharma to treat Duchenne muscular dystrophy.
The Alex’s Wish funding is helping to speed up the Duchenne clinical trials, providing the first funding for setting up the trials in the US and Europe, as well as funding a GMP drug synthesis for these trials. The funding is also enabling innovations in biomarker studies through as benchmarking of VBP15 against Prednisone in mice with muscular dystrophy. These innovations in biomarkers could help speed the development of many other drugs in Duchenne, and other types of muscular dystrophy.
VBP15 has been shown to be effective in animal models of Duchenne muscular dystrophy, and clinical trials in humans are now under way. In studies, the drug reduced inflammation and stabilised cell membranes, both of which are believed to be relevant to treating Duchenne, a disease in which muscle fibre membranes are unstable. The drug is thought to have similar properties to steroids such as Prednisolone and Deflazacort, which up until now have been the cornerstone of treatment for boys with Duchenne. The benefit of VBP15, however, is that it is thought to have significantly fewer side effects than existing steroids, which can be life changing in themselves. Side effects include diabetes, high blood pressure, osteoporosis, short stature and weight gain.
Clinical Research Infrastructure:
Awarded a Fellowship to a vital Duchenne Researcher
Alex’s Wish is part of a consortium of charities working on Duchenne Muscular Dystrophy that has awarded a Fellowship to Dr Michela Guglieri in partnership with Newcastle University and Newcastle University Teaching Hospital to develop and advance the clinical trial agenda for this devastating and currently incurable condition. The group of charities: Alex’s Wish, Action Duchenne, Duchenne Children’s Trust, Duchenne Now, Duchenne Research Fund, Harrison’s Fund and Joining Jack all have a shared goal to bring new treatments to the clinic for Duchenne muscular dystrophy as quickly as possible.
The award of £250,000 over five years is being matched by Newcastle University to enable Dr Guglieri to develop the clinical trial capacity for Duchenne at the John Walton Muscular Dystrophy Research Centre and nationally via work on a range of different projects which will consolidate knowledge on the best way to run trials for DMD. There are currently eight trials in DMD ongoing at the Clinical Research Facility at NUTH supported by the John Walton Muscular Dystrophy Research Centre and by the NIHR CRN. Several new studies are also on the horizon.
About the John Walton Muscular Dystrophy Research Centre
The John Walton Muscular Dystrophy Research Centre brings together and consolidates Newcastle’s distinguished, international and world-leading record in research and care for neuromuscular diseases. The team of over 70 people based at Newcastle University and its associated hospitals work together towards the development and application of genomic and translational medicine to improve the health outcomes of people living with neuromuscular diseases. As a group, the Centre has developed a close and important link between research and clinical activities and actively pursues new partnerships with other stakeholders such as patient organisations, regulators and pharma. The John Walton Centre’s key areas of activity – including clinical care, research, diagnostics and networking – all are strongly interlinked. It is the collaboration and work across these teams that are key to the Centre’s success and impact in the neuromuscular field.
The Newcastle Plan
There is an increasingly community wide focus on clinical trial capacity in the UK, and Treat-NMD has coordinated and organised a national meeting in Newcastle concerning the apparent lack of capacity for trials in Duchenne. This brought together 75 stakeholders representing patient organisations, clinical experts, the pharmaceutical industry, as well as the National Institute for Health Research (NIHR), to develop a strategy to improve capacity and better utilise existing resources.
All stakeholders contributed to shaping ‘the Newcastle Plan’, published after the conclusion of this meeting and encapsulating the key areas of discussion. This document concluded that the UK must maintain its place as one of the key “go to” countries for clinical trials in Duchenne, positing a five year objective to ensure that all patients with Duchenne, children and adults, have access to clinical research opportunities. Intermediary objectives were also established aiming to stop the UK turning trials away and develop excellence and capacity at existing sites.
To read the full Newcastle Plan summary document, published by Treat NMD, please click here. To read a summary of discussions at the first patient organisation steering group meeting in September 2015, click here. Alex’s Wish has agreed to fund £29k into the Newcastle Plan for a Clerical Assistant Post in Newcastle for 1 year and we are hoping to invest more funds over the coming months.
Update on the Newcastle Plan – August 2016:
In December 2015, eight patient organisations, who are working to help support clinical trial development for Duchenne muscular dystrophy, announced £1.2million of investment, to fund sixteen clinical posts.
We are pleased to announce that TEN of those SIXTEEN posts have now been recruited.
The posts are at Great Ormond Street Hospital in London, The John Walton Muscular Dystrophy Research Centre at Newcastle University, University Hospitals Bristol NHS Foundation Trust and Alder Hey Children’s Hospital in Liverpool.
The funding was put together in just six months, after an unprecedented meeting in Newcastle in July 2015 – out of which came the Newcastle Plan – where patient organisations, clinicians, representatives from industry and from the NHS and the National Institute of Health Research, gathered together to address the lack of capacity for Duchenne research at neuromuscular centres in the UK.
NOW, only thirteen months after the workshop, there are already ten research-related posts in place all over the UK, making a difference to patients and their families TODAY.
These posts are funded by: Action Duchenne, Alex’s Wish, Duchenne Now, Duchenne Research Fund, Duchenne UK, Harrison’s Fund, Joining Jack, MDUK, the GOSH NHS Trust and Great Ormond Street Hospital Charity.
Here are details of the posts:
The John Walton Muscular Dystrophy Research Centre at Newcastle University
- Clinical Trial Co-ordinator in post
- Research Physiotherapist appointed
- Administrative post, Nurse and Clinical Research Associate close to appointment
Alder Hey Children’s Hospital in Liverpool
- Research Physiotherapist in post
- Trials Co-ordinator and Clinical Fellow currently recruiting
Great Ormond Street Hospital in London
These posts are being funded in collaboration with the GOSH NHS Trust and GOSH charity
- Two Clinical Research Fellows appointed
- Two Research Physiotherapists posts appointed
- Physiotherapy Assistant appointed
- Clinical Trial Co-ordinator appointed – with support from the family of Jacques Joubert
- A senior lecturer is close to appointment
- Professor and Data Manager being recruited
University Hospitals Bristol NHS Foundation Trust
- Clinical Research Physiotherapist being recruited