What is drug repurposing?
Drug repurposing, also known as drug repositioning, is the process of finding new uses for old or existing drugs. Researchers take a drug that’s already been approved to treat one patient population and investigate via clinical trials if it can be an effective and safe treatment for another condition entirely. Drug repurposing is a lot like recycling and has become the cheaper and faster way to bring treatments to market, especially for those living with rare and ultra-rare diseases!
What are the benefits of drug repurposing?
Besides being a cheaper and faster way to deliver treatments to patients, drug repurposing also provides the following benefits:
- It removes the need for de novo (“new”) drug discovery and candidate synthesis, the process of identifying a drug with a strong therapeutic potential pre-clinical trial, since the compound being repurposed already exists.
- Researchers already know how the drug will enter, move through and exit the body, which makes the drug’s absorption, distribution, breakdown and excretion no mystery to those studying it. This upfront knowledge allows researchers to save time, money and resources by only screening a few vs. thousands of candidates before a clinical trial.
- Since the drug in question has already been used in a variety of different age groups and body types, the drug’s safety profile is well understood. This speeds up the drug development process for researchers because they can conduct a reduced safety trial before working to determine the proper dosage.
- Drug repurposing has a high likelihood of success and progressing to the market faster than drugs which have been developed from scratch using the de novo method.
Drug repurposing helps to mitigate the challenges associated with orphan drug development, such as small patient populations, money and time, and has proven to be a new, attractive alternative to researchers, industry and pharma who want to get involved in rare disease research and treatment!
How drug repurposing relates to MCDS-Therapy
For all the reasons outlined above and more, the MCDS-Therapy consortium have turned to drug repurposing in the hope of finding a new treatment for metaphyseal chondrodysplasia type Schmid, or MCDS. We have identified the drug, Carbamazepine, as a potential treatment for MCDS, which was originally used to treat epilepsy and bipolar disorder in the 1960s!
Repurposing Carbamazepine to treat MCDS
We know that MCDS is caused by an error in the body’s genetic code on the COL10A1 gene, which results in the protein, collagen X (collagen 10), being built incorrectly and getting trapped in the cell’s endoplasmic reticulum (or ER). Collagen X is only produced at the ends of bones in the cartilage growth plate, so when collagen X gets trapped or “stressed” (ER stress), the cell slowly begins to die and starts to hinder one’s bone growth. This results in the symptoms of MCDS, such as disproportionately short limbs, bones flaring at their ends, short stature and curvature of the long bones, amongst other painful symptoms.
Knowing what results from this gene mutation, our team conducted an experiment to prove that ER stress was in fact the underlying cause of MCDS; first by creating ER stress within growth plate cells that were unaffected by MCDS and later with mice models. We were proven correct in both models, leading us to progress to the next stage: identifying a drug that could effectively reduce ER stress in growth plate cells. As you can guess, Carbamazepine proved to reduce ER stress the most in both our cell and mice models, making it the perfect drug to repurpose as a potential treatment for MCDS. After all, it’s been 25 years and we still don’t have a treatment!
Current Status
We’re thrilled to say that we have officially relaunched the MCDS-Therapy clinical trial at both our UK sites after having to halt our trial in response to COVID-19. We’ve officially moved onto the dosing stage of the trial and have successfully dosed our first patient with carbamazepine in December 2020.
We look forward to more patients receiving the drug in the coming months so that we can confirm the appropriate dose of carbamazepine to give to patients. From there, we’ll focus our efforts on proving that carbamazepine is an effective and safe treatment for MCDS, so stay tuned for the results of our EU-funded clinical trial and read up on the Science of MCDS-Therapy learn more!
More about drug repurposing and MCDS from our consortium
Findacure CEO, Dr. Rick Thompson, and Professor of Skeletal Genetics, Newcastle University, Professor Michael Briggs, discuss drug repurposing and the MCDS-Therapy clinical trial at Findacure‘s 2018 Drug Repurposing conference. Watch their presentations below now to learn more and let us know what you think on Twitter and Facebook!
For rare disease patient groups, academics and researchers
If you or your rare disease patient group are thinking about setting up a drug repurposing project, read Findacure’s in-depth drug repurposing guide to learn what needs to be considered before getting involved in drug repurposing research. There you’ll find additional examples of drug repurposing projects and all the information you need to begin your journey with a clear focus.
View Drug Repurposing Guide
Don’t have time to read through the guide? Watch Findacure CEO, Dr. Rick Thompson, present on drug repurposing during Findacure’s drug repurposing workshop below!
Please note: The Drug Repurposing workshop upon which this guide was based, and Findacure’s own work in developing this guide, was completed in collaboration with the MCDS-Therapy Consortium. The work was partially funded through their grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754825.
