DISCOVERY OF THE FOP GENE

It began with our support of basic science, the backbone of all therapeutic development. For 34 years the IFOPA has been supporting the Center for Research in FOP & Related Disorders at the University of Pennsylvania. The discovery of the FOP gene in 2006 was a direct result of IFOPA funding and the efforts of FOP community volunteers to find multi-generational families whose blood work would reveal the FOP gene. UPenn’s work continues to deliver groundbreaking results including the Resilient Patient Project published in 2024.

FOP BIOBANK

In 2018, the IFOPA launched a dedicated effort to collect biosamples from people living with FOP. FOP researchers need these biosamples (blood, urine, saliva and “baby teeth”) to make new discoveries, test new drugs, and look for new disease markers in FOP. Not only have we funded the preparation and storage of these samples, we’ve funded three collection events (soon to be 4) at FOP Family Gatherings to collect samples from people with FOP and their relatives who serve as healthy controls. We're grateful to Dr. Dan Perrien of Emory University for managing the IFOPA's FOP Biobank.

GENE THERAPY

Five years ago, we innovated once again when we launched the In Pursuit of a Cure campaign to fund the first gene therapy grants for FOP. We started with an idea. Could AAV9 gene therapy be used in FOP?

AAV-based gene therapies are being investigated in a variety of diseases, including rare diseases, neurological diseases, hematological diseases, and musculoskeletal disorders. As of May 2024, there have been more than 250 clinical trials worldwide using AAVs. The team at the University of Massachusetts (UMass) who received the first grants have proven in FOP mice that gene therapy can work.

The initial data was published in the prestigious journal Nature Medicine in late 2022. Now we need a commercial partner to take what the University of Massachusetts has found and move forward toward developing a clinical trial.

SILENCING RNA

But the promise of gene therapy goes beyond these initial findings. After being introduced to FOP through the AAV9 work of Jae Shim's lab at UMASS, another team became interested in how their genetic medicines could be used to treat FOP. Julia Alterman (who you heard from at last year's In Pursuit of a Cure event) and her team are developing a silencing RNA therapy for the treatment of FOP. At the IFOPA’s Drug Development Forum (DDF) held in June in Stockholm, two members of Dr. Alterman’s lab shared their work. Their session “RNA Therapeutics and Stem Cell Delivery” was one of the highest rated of the Forum.

DRUG DEVELOPMENT FORUM

Speaking of the DDF, the IFOPA just hosted its sixth event – the only research meeting in the world dedicated to the sharing of scientific studies and clinical trials in FOP. The DDF fosters collaboration among all members of the FOP research and development pipeline through the sharing and discussion of emerging FOP data, highlights gaps in our understanding of FOP disease pathogenesis that could offer new therapeutic options, and creates opportunities for biotech and pharmaceutical companies, academic researchers and clinician scientists to take on shared challenges.

In 2024, there were nearly 200 attendees representing 43 academic centers and hospitals, 9 pharmaceutical & other corporate entities, and 17 patient organizations.

STOPFOP CLINICAL TRIAL

At the DDF we heard the latest updates on an investigator-led trial that the FOP community has played a major role in making possible.

The aim of the Saracatinib Trial to Prevent Fibrodysplasia Ossificans Progressiva (STOPFOP) was to investigate the drug AZD0530, also known as saracatinib, to see if it could stop the advancement of bone growth in FOP patients. The research team had already demonstrated that the medicine was effective in mice; if it worked the same way in humans, it would be a significant discovery.

Only a few weeks into recruitment, the world shut down due to the COVID-19 pandemic, and STOPFOP recruitment paused with it. The few patients who had already enrolled continued on with the trial throughout 2020, receiving the drug under the direction of the principal investigator, but new patients could not enroll until October 2020.

Recruiting participants during a global pandemic was hard and the funding the STOPFOP trial had secured from the European Commission Innovative Medicine Initiative would run out before all of the needed participants could enroll and complete the 18-month trial.

The IFOPA recognized the importance of the STOPFOP trial and stepped in to provide three years of support for the principal investigator. Because that cost was now covered, the STOPFOP team was able to secure other grants to cover additional trial expenses, including nearly £725,000 from LifeArc, a UK-based funder. Clinical trials are very expensive and other FOP organizations and family fundraisers have joined in to support the STOPFOP trial as well.

ALTERNATIVE IMAGING OPTIONS

All drugs that are going through clinical trials have endpoints which are measures of whether or not the drug is working. In FOP, bone growth is an endpoint. Currently available methods to measure new lesions and increased bone growth are expensive, require high degrees of training to perform and analyze, and can often be inaccessible for FOP patients with permanent changes in their mobility and body positioning caused by the condition. Even more importantly, the sensitivity of current methods requires a minimum of 6-12 months to detect a statistically significant change in the number of new lesions or total bone volume. This results in very long clinical trials.

The IFOPA is looking for new — more efficient, safe, noninvasive, and user-friendly —approaches that should be capable of measuring new bone formation (or lack thereof) in no more than 3-6 months. We’re also funding the exploration of ultrasound to measure new bone growth through an ACT for FOP grant funded this year.

MUSCLE REGENERATION

As drugs are approved to stop bone growth in FOP, the next question that begins to be asked is, could we give people this drug and then do surgery to remove the heterotopic bone? While surgery to remove FOP bone is being studied, a key question is if you remove FOP bone that has replaced the muscle, can you regrow the original muscle so that people with FOP can move without restrictions? One of the ACT for FOP grants funded this year will explore the science of muscle regeneration should surgical removal of bone be a possibility one day.