MCDS-Therapy

We were part of the EU Horizon 2020 funded project for the ultra-rare disese MCDS.

MCDS-Therapy

Beacon was part of an EU-Horizon 2020-funded project that tested whether the drug carbamazepine could be repurposed to treat the ultra-rare bone disease, metaphyseal chondrodysplasia type Schmid (MCDS).

MCDS-Therapy worked to prove that carbamazepine was not only safe to use but also effective in reducing the pain and mobility difficulties experienced by MCDS patients.

MCDS-Therapy aimed to deliver the first non-surgical therapeutic intervention for MCDS.

MCDS Logo

What is Metaphyseal chondrodysplasia schmid type (MCDS)?

MCDS, or metaphyseal chondrodysplasia type Schmid, is an ultra-rare inherited bone disease, which leads to:

  • Short stature with disproportionately short arms and legs (Short-limbed dwarfism)
  • Curvature or bowing of the leg bones (Genu varum)
  • Ends of long bones and ribs flaring outward
  • Hip deformities causing the thigh bone to be angled towards the centre of the body (Coxa vara)

The characteristics listed above can result in an impaired gait, which makes walking difficult. Pain in the legs and joints tend to be experienced throughout life.

About MCDS-Therapy

MCDS-Therapy received funding from EU Horizon 2020 to test whether the drug carbamazepine (CBZ) could be repurposed to treat the ultra-rare bone disease, metaphyseal chondrodysplasia type Schmid (MCDS). CBZ was originally used to treat epilepsy and bipolar disorder in the 1960s!

The project ran from 2018 until 2024 after the EU granted the project an extension due to unforeseen delays from the global COVID pandemic. Beacon was one of 11 international consortium members working on this project, which included a clinical trial and sub-projects that evaluated the health economics of CBZ and biomarker development. Before MCDS-Therapy, a comprehensive health economic assessment had rarely been undertaken for a rare bone disease and no biomarker signature existed for any rare bone disease!

What is a biomarker?

A biomarker can be a molecule, a gene, a cell, or any other measurable characteristic found in your body that indicates if something is standard or not. Think of a biomarker like a signal or a flag.

Biomarkers help detect diseases early, sometimes even before you have any symptoms. They can be used to monitor the progress of a disease or how well a treatment is working.

What is a biomarker signature?

A biomarker signature is a unique fingerprint for a disease or health condition.

Imagine a biomarker as a clue that doctors or scientists look for in your body. It could be something in your blood, like a protein, or a pattern in your genes.

Biomarkers help tell what’s going on inside your body.

A biomarker signature isn’t just one clue, but a combination of several clues put together. It’s like solving a puzzle – each piece (biomarker) adds to the whole picture (signature).

About the health economics work

A comprehensive health economic assessment of the socio-economic burden of MCDS and the potential benefit of pharmacological intervention was completed.

A Qualitative study to explore the perceptions and experiences of patients and caregivers living with a rare bone disease was also completed. The Health Economics team conducted 15 one-to-one interviews to complete this study, hearing their stories and personal experiences of what it’s like to live with a rare bone disease.

Building off this qualitative study, the MCDS-Therapy health economics team conducted a quantitative study of preference elicitation. A discreet choice experiment and assessment of marginal willingness to pay was then conducted through a survey that was open to anyone living with a rare bone disease, musculoskeletal condition, or specific childhood cancers from around the world. The survey and discreet choice experiment could be taken in English, Spanish and Italian, and saw an overwhelming 190 responses!

What is a qualitative study?

Instead of using numbers and statistics, a qualitative study explores people’s experiences, feelings, and opinions. It aims to gain a deep understanding of a topic.

Researchers gather detailed information by talking to people, observing them, or analysing written content.

What is a quantitative study?

A quantitative study collects data that can be counted or measured. It uses mathematical and statistical methods to analyse data, making it more objective and less influenced by personal opinions or feelings.

Researchers often use surveys to ask a lot of people the same questions. The answers are usually in the form of numbers or choices.

Researchers then use statistical software and methods to look for patterns and relationships in the collected data.

What is preference elicitation?

Preference elicitation is a way to figure out what people like or prefer when they have choices.

It’s about learning what someone would pick or prefer when given different options. For example, if you’re trying to decide on the best movie to watch or which features you want in a new phone, preference elicitation helps identify those choices.

What is a discreet choice experiment?

A discrete choice experiment (DCE) is a research method used to understand how people make choices when they are presented with different options.

In a DCE, people are given a set of options and they must choose one. Each option has different characteristics or features.

Researchers create scenarios where each option has a mix of attributes. For example, if it’s a study about cars, the attributes might include price, color, fuel efficiency, and brand.

Participants are shown these scenarios and asked to pick the option they prefer the most in each scenario. This is done multiple times with different combinations of attributes.

By analysing the choices people make, researchers can understand what attributes are most important to them. For example, they can tell if people care more about the price or the brand of a car.

DCEs help predict how people might choose in real life based on different factors, which is useful for businesses and policymakers.

DCEs help researchers learn what people value most in the options they choose.

 

About the MCDS-Therapy clinical trial

MCDS-Therapy was the first academic-led drug repurposing clinical trial for a rare bone disease!

MCDS-Therapy recruited patients at four trial sites (Newcastle, London, Melbourne and Bologna) from three countries for the first-ever clinical trial for the ultra-rare bone disease, metaphyseal chondrodysplasia type Schmid (MCDS).

In total, 27 patients were recruited for the clinical trial across four trial sites and three countries. The recruitment goal for the clinical trial was 40 participants.

The consortium’s statement on the use of Carbamazepine (CBZ)

“Preliminary results of the MCDS-therapy trial of the use of carbamazepine (CBZ) in children with Metaphyseal Chondrodysplasia Schmid type (MCDS) are now available. These results suggest that carbamazepine is safe to use in children with MCDS and is associated with similar side effects in this group of children to those seen in children who do not have MCDS. These side effects are less in children on lower doses of CBZ. We treated participants in MCDS-Therapy with a maximum of 20mg/kg/day of CBZ.

The results suggest that some children with MCDS who take CBZ may find that there is a reduction in the pain they feel and their growth rate may be a little faster than in those children who do not take CBZ. The results on growth in particular are not final and do not show a definite increase in growth rate. It is possible that CBZ may slow the progression of some of the abnormal changes in bone growth seen in MCDS at the hips and knees.

It is very important to emphasise that these are preliminary results and we need to do more work on the information we have from the trial to understand whether our assumptions are correct.

Doctors may want to consider treatment with CBZ in children with MCDS but this has to be only after careful discussion between the family and the doctor balancing the risk of side effects with the possible improvements in pain and growth. CBZ is not licenced for the treatment of MCDS and so doctors will need to consider whether the regulations in their country allow the prescription of the drug to children with MCDS. If children with MCDS are treated with CBZ they should be closely monitored throughout treatment. We will be issuing further information about our suggested monitoring regime in the next few months.

This statement is not a recommendation of CBZ for use in children with MCDS by the MCDS consortium and we do not accept responsibility for any effects of treatment with CBZ in children with MCDS.”

 

Beacon’s role in MCDS-Therapy

Beacon was responsible for the external communications and patient engagement work at MCDS-Therapy.

We maintained the official MCDS-Therapy website and ran the project’s social media channels. We built a supportive community of rare bone disease patients, families, researchers and clinicians through the MCDS-Therapy’s Facebook and Twitter profiles and quarterly newsletters.

Beacon brought the patient experience to the forefront of the consortium’s work. We met with MCDS and skeletal dysplasia patients, shared their stories on the MCDS-Therapy blog and sought their feedback through surveys and focus groups. Patient responses were highlighted and shared by us at consortium meetings to ensure that the patient voice remained at the forefront of our work.

We championed the patient voice and ensured that patients remain at the heart of the MCDS-Therapy project and clinical trial.

Beacon highlight

On 30th May 2024, the MCDS-Therapy consortium hosted the MCDS-Therapy Final Conference at The Catalyst in Newcastle, UK and online. The final conference was organised by us and was our first hybrid event!

The conference was a brilliant event, offering a platform for insightful discussions between the rare bone and MCDS community. It was fantastic to hear the stories of those involved with the MCDS-Therapy clinical trial and project, from patients and families to researchers and healthcare professionals from around the world.

Join the new MCDS patient registry!

Because of the success of MCDS-Therapy, a new MCDS patient registry was launched by Newcastle Hospitals!

If you/your child has a diagnosis of MCDS, then you’re eligible to join this international registry!

If you have any questions, don’t hesitate to contact the registry coordinator: sam.mcdonald@newcastle.ac.uk

Further advice and support

If you’d like further support with living with a rare bone disease or skeletal dysplasia, view MCDS-Therapy’s curated list of organisations that can help!