Novel, point of care biomarker to detect pre-clinical flares for people living with fibrodysplasia ossificans progressiva (FOP)

Awardee: Nezihi Murat Karabacak

Institution: Massachusetts General Hospital

Grant Amount: $64,000

Funding Period: February 1, 2022 - January 31, 2023

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Summary:

Fibrodysplasia ossificans progressiva (FOP) is a severely debilitating condition with no accurate and clinically applicable biomarkers or imaging approaches. Our overall goal is to develop a novel, non-invasive assay to detect the initiation and progression of FOP. We will define a series of novel blood-based biomarkers specific for monitoring heterotopic ossification predicated in people living with FOP. As a result, we will establish an innovative way to detect and evaluate progression and monitor treatment outcomes for this disease process.

Role of the GM-CSF Pathway in Heterotopic Ossification Associated with Fibrodysplasia Ossificans Progressiva (FOP) and Novel Therapeutic Strategies to Suppress the Inflammatory Response

Awardee: Eileen M. Shore

Institution: University of Pennsylvania School of Medicine

Award Amount: $40,000

Funding Period: February 1, 2021 - January 31, 2022

Influence of microbiota on innate immune responses and heterotopic ossification in fibrodysplasia ossificans progressiva (FOP)

Awardee: Daniel Perrien

Institution: Emory University

Award Amount: $40,000

Funding Period: February 1, 2021 - January 31, 2022

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Summary:

Fibrodysplasia ossificans progressiva (FOP) is a currently untreatable genetic disease in which skeletal muscle repair is misdirected to endochondral bone formation (heterotopic ossification, HO) causing pain, muscle destruction, and joint fusion, leading to progressive immobilization and eventually premature death.  Despite the monogenetic cause of FOP (gain-of-function point mutations in ACVR1/ALK2), disease severity and progression vary widely among patients with the same mutation, suggesting additional factors such as background genetics, environmental, or nutritional influences can modify the course of disease. Exciting preliminary data demonstrate that ablation of the gut bacteria (microbiota) in FOP mice reduces injury induced EHO. This project will determine whether introduction of specific anti-inflammatory bacteria to the gut microbiota can regulate the severity of injury-induced flares in FOP mice. Unlike commercially available supplements, the probiotics in these studies will include highly potent live bacteria specifically selected for their newly discovered roles in regulating musculoskeletal diseases.  If our hypothesis is proven correct, these studies may form the foundation for a clinical trial in FOP patients and multiple applications for NIH funding.

Eludicating the role of marrow-resident myeloid cells in FOP

Awardee: Shailesh Agarwal

Institution: Brigham and Women's Hospital, Harvard University

Award Amount: $40,208

Assessment of Disease Activity in FOP Patients using Electrical Impedance Myography

Awardee: Jaymin Upadhyay

Institution: Boston Children's Hospital, Harvard Medical School

Award Amount: $40,208

Publications:

Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography

Synthetic CT Assessment of Lesions in Children With Rare Musculoskeletal Diseases

Role of the GM-CSF Pathway in Heterotypic Ossification Associated with FOP

Awardee: Eileen Shore

Institution: University of Pennsylvania

Award Amount: $37,633

Funding Period: February 1, 2019 - January 31, 2020

Profiling macrophage transcription in FOP

Awardee: David Mosser

Institution: University of Maryland

Award Amount: $37,633

Funding Period: February 1, 2019 - January 31, 2020