Home » Rare diseases » Accelerating rare disease drug discovery by combining research and therapeutics development

Professor Matthew Wood

Director, Oxford-Harrington Rare Disease Centre

Jonathan S. Stamler, MD

President, Harrington Discovery Institute

Rare disease research and drug discovery require collaboration between patients, organisations, researchers and clinicians. Only then can treatments for the millions of people with a rare disease become a reality.

Only a small percentage of people living with a rare disease have an approved therapy for their condition, presenting a great challenge to global health.

Turning promise into action

Most rare diseases have a genetic cause, resulting from variations in a person’s DNA. With recent developments in genomics and the ability to quickly and cost-effectively sequence patients’ DNA, there is now the exciting opportunity to design personalised medicines for rare diseases.

The Oxford-Harrington Rare Disease Centre (OHC), a partnership between the University of Oxford and Harrington Discovery Institute, is combining world-leading research with expertise in therapeutics development to accelerate the discovery and delivery of new treatments for rare diseases.

New hope for patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease characterised by progressive muscle degeneration and weakness. DMD is caused by a defect in a gene that makes dystrophin, which acts like a shock absorber when muscles contract. Without dystrophin, muscles progressively become damaged and weakened. People with DMD typically do not live past their 30s.

Angela Russell, Professor of Medicinal Chemistry at Oxford, has been working on a protein called utrophin, which was found to function similarly to dystrophin in protecting muscle. Her group has discovered new classes of molecules that increase utrophin production. Her project was recently selected by the OHC for further drug development and commercialisation support.

We are now in a position to make a difference for people who have had little hope of finding a treatment.

Matthew Wood

Innovative technologies: DNA repeat expansion disorders

Huntington’s disease (HD) is a fatal disease that causes certain brain cells to degenerate. Symptoms include uncontrolled movements and difficulty walking. HD results from a disease-causing DNA repeat expansion, wherein a segment of DNA within the huntingtin gene expands.

Edward Grabczyk, Professor of Genetics at Louisiana State University and Harrington Rare Disease Scholar, identified that the genetic mutation underlying DNA repeat expansion in HD is driven by the protein MLH3. He designed novel oligonucleotide drugs to decrease MLH3 activity, which in turn should slow or stop the progression of the disease. Grabczyk’s approach may enable the treatment of other related disorders, and today, his technology is licensed with Takeda Pharmaceuticals.

The OHC has a philanthropically funded programme focussed on Friedreich’s ataxia, a neurodegenerative rare disease with a related disease mechanism. It works with an international network of patients, foundations, researchers and clinicians towards developing new therapies for the one in 40,000 people affected by this disease.

Advancing treatments towards patients

Harrington Discovery Institute is an international drug discovery and development organisation established to address unmet therapeutic needs. It provides comprehensive support to leading scholars and entrepreneurs across academic centres in the US, UK and Canada. The focus is on medical breakthroughs that show great promise but would not otherwise advance to clinical trials.

By concentrating on philanthropic, scientific and business development resources during the early, high-risk stage of drug discovery and creating pathways toward commercialisation, Harrington drives the progress of therapeutic candidates towards further investment and clinical trials.

Partnering for cures

The University of Oxford has hundreds of researchers working on a range of rare diseases and cutting-edge therapeutics. Its new Institute of Developmental and Regenerative Medicine (IDRM), where the OHC is based, aims to develop new drugs and therapeutic strategies for neurological, cardiovascular and immune diseases.

Matthew Wood, Director of the OHC, Professor of Neuroscience at Oxford’s Department of Paediatrics, and Director of the MDUK Oxford Neuromuscular Centre, recognises the need for partnership with the global rare disease community in achieving the goal of accelerating rare disease therapeutic development. Wood explains: “There are significant challenges in meeting the needs of rare diseases. With advances in genomics and drug development and delivery, we are now in a position to make a difference for people who have had little hope of finding a treatment.”

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