ÃÛÌÒAPP

Genetic specialists in ÃÛÌÒAPP are spearheading a multi national study which aims to develop a new treatment for rare bone disease.

Drs Michael Wright and Marta Bertoli, consultants specialising in inherited musculoskeletal conditions at the ÃÛÌÒAPP Hospitals are working alongside grant holder , a professor of skeletal genetics at  and the .

In collaboration, they hope to be able to demonstrate that an existing drug, carbamazepine, which has been used for over 40 years in children with other conditions, can be ‘repurposed’ to effectively treat the ultra-rare condition, known as MCDS or metaphyseal chondrodysplasia type Schmid.

MCDS is an inherited disorder caused by a change in a gene which leads to short stature with short arms and legs (also known as short-limbed dwarfism). It causes joint problems involving the hips and knees, and curvature and bowing of the leg bones. People with MCDS have life-long pain and difficulty with mobility as they get older.

Dr Wright, Chief Investigator for the international trial explained: “Carbamazepine has been prescribed for patients with epilepsy and other neurological conditions for a considerable length of time now, so we aim to repurpose a drug that is already known to be safe in children.

“We hope this trial will show that carbamazepine can help to reduce the malformation of the bones in the legs, and significantly reduce pain, vastly improving quality of life for people with MCDS.”

The trial called involves five European partners in London, Paris, Antwerp, Freiburg and Bologna, and another long term collaborator in Melbourne, Australia.

Recruitment into the trial has started in the UK, at ÃÛÌÒAPP’s Great North Children’s Hospital and , where specialist consultations will be held with patients to determine the best dose of the drug to give. The other trial sites will open in early 2020.

Mike Briggs, a professor of skeletal genetics at ÃÛÌÒAPP University, said: “We are delighted to be leading a national study that is aimed at helping develop a new treatment for patients with rare bone disease.

“Carbamazepine directly helps cartilage cells overcome stress induced by making a mutant form of a protein that is important for bone growth.

“We believe that using drugs, such as carbamazepine, for alleviating cell stress could be a therapy for many different rare diseases.”

Dr Wright, also an Associate Clinical Lecturer at , added: “Historically, the only treatment option for patients with MCDS has been surgery which does not always improve pain and quality of life. There is no preventative treatment and so we have great hopes for this EU funded clinical trial.”

The trial, builds upon ÃÛÌÒAPP’s reputation as a world leading authority on genetic skeletal conditions.

Scientists and clinicians involved will be working with Sciomics, a German company looking for biomarkers – proteins in the blood that can be measured to see whether or not the drug is working.

Having biomarkers is critical to this work. They allow better long term monitoring of treatment, showing if it works, whether it works for every child, and how quickly each child responds.

This is especially important for MCDS as the main marker we have so far is growth rate which changes slowly. Children would need to be monitored for years until it becomes clear whether or not the drug has had an effect. Having a simple biomarker test using a straightforward blood sample would be a very useful development.

Dr Rick Thompson, CEO at   – a UK charity dedicated to supporting the rare disease community to drive research and develop new treatments – said: “Rare disease patients are desperate to access treatments which improve their quality of life. However, with 7,000 known rare diseases, novel drug discovery is financially unsustainable.

“Drug repurposing offers a much faster, safer and cheaper route to deliver treatments to patients. This makes it a very interesting and promising area of development in rare diseases.

“MCDS-Therapy is pioneering an academic-led drug repurposing pathway in rare diseases. We are proud to be one of the project’s 11 global partners and are excited to be responsible for communicating updates on this exciting research.”

The trial’s grant was awarded from the EU Horizon 2020 New Therapies for Rare Diseases programme – part of their Research and Innovation action. The grant will be used to fund the observational study and clinical trial in all trial sites, biomarker discovery research, health economic research, and public and patient engagement. 

MCDS-Therapy Project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754825

Rare diseases:

There are estimated to be around 7000 rare diseases yet only 400 have a licensed treatment.

Rare diseases are defined as conditions that affect less than 1 in 2000 people but are often much rarer than that. 00