These Million Dollar Bike Ride Pilot Grants were made possible by the fundraising efforts of Joseph Walewicz, Joe Martucci, Elizabeth Wolensky and the AJ Gonazales family. We are also grateful for a supportive gift from Clementia, as well as a generous match from the Penn Medicine Orphan Disease Center.
2018 Grant Awardees
Profiling Macrophage Transcription in FOP
Principal Investigator: David Mosser, PhD
Institution: University of Maryland
Country: United States
Award Amount: $37,633
Project Description: The episodic misplaced bone growth (heterotopic ossification) of FOP has been associated with inflammatory flare-ups in connective tissue following trauma. Dr. Mosser’s research seeks to understand how the inflammation that accompanies muscle trauma can lead to heterotopic ossification. This study will focus on one important host inflammatory cell; the activated macrophage. Macrophages from a mutant mouse carrying the FOP mutation will be stimulated, and their response to stimulation will be compared to macrophages from a normal mouse. Dr. Mosser hypothesizes that differences in gene expression between mutant and wild-type macrophages, at either the onset or the resolution of activation, may begin to reveal critical components of macrophage biology that contribute to FOP disease progression. The ultimate goal of these studies is to understand how macrophages contribute to the process of heterotopic ossification in FOP.
Role of the GM-CSF Pathway in Heterotypic Ossification Associated with FOP
Principal Investigator: Eileen Shore, PhD
Institution: University of Pennsylvania
Country: United States
Award Amount: $37,633
Project Description: The genetic cause of FOP is known to be heterozygous mutation of the ACVR1 gene, however the understanding of the cellular mechanisms that are altered by the gene mutation and lead to HO remains limited, restricting new strategies for drug development and treatments for FOP. Heterotopic ossification (HO) in FOP is often preceded by inflammatory ‘flare ups’ and recent lab studies in an FOP mouse model have further supported that inflammation and immune cells, notably mast cells and macrophages, provide important influences on HO formation. Dr. Shore’s research will elucidate the role of a potential inflammatory pathway, the GM-CSF pathway, that may support FOP pathophysiology and early stages of HO formation. GM-CSF is a major mediator of inflammation regulating many inflammatory cells including mast cells and macrophages. This research will examine the in vivo impact of a neutralizing anti-murine-GM-CSF antibody on HO formation in an Acvr1R206H FOP mouse. Confirmation that the GM-CSF pathway plays a direct or indirect role in HO may lead to new strategies to better define the specific cellular pathways associated with HO in FOP and offer new agents to treat and/or manage the disease, including near-term clinical trials using existing anti-GM-CSF monoclonal antibodies that have already been used in human clinical trials.
