2024 – 

Title: Validation of extracellular vesicle-associated circulating biomarkers for FSHD in cross-sectional & longitudinal clinical studies

Principal Investigator: M. Bilal Bayazit researcher/ in Nizar Saad lab – Nationwide Children’s Hospital at Ohio St. University

Aim 1: To determine the RNA and protein content of EVs from FSHD patient plasma in independent cohorts for the identification of prospective EV-associated FSHD biomarkers. This aim will serve as a study to compare RNAs and proteins found in EVs extracted from plasma collected from FSHD patients and healthy controls. Our goal is to identify EV-associated RNA and protein signatures for FSHD, and to validate our identified molecular biomarkers in two independent patient cohorts. We will correlate the identified molecular signatures with disease severity (clinical severity score) and confounding factors (i.e., age, and sex). Considering the heterogeneity of FSHD, this aim will address the specificity of biomarkers against multiple factors. Our goal is to identify unique plasma EV- associated RNA and protein signatures in FSHD patients that can be used to predict disease progression, stratify patients for clinical trials and assess efficiency of therapies used in clinical trials.

Award Amount: $115,000 – 1 year project *Co-funded with Friends of FSH Research

2023 – 

Title: Bio-marker Study

Principal Investigator: Dr. Nizar Saad, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital – Columbus, OH

The project is part of an ongoing pilot cross-sectional clinical study with Dr. Scott Harper and Dr. Kevin Flanigan to recruit up to 25 FSHD patients to validate alterations in therapeutically relevant biomarkers in muscle tissue from FSHD patients, to assess correlation between the expression of relevant biomarkers and clinical functional measures and to assess the utility of muscle MRI in identifying regions of muscle suitable for sampling for relevant biomarkers. 

Award Amount: $110,000

Title: MRI Imaging to Identify Bio-markers for porcine large animal models

Principal Investigator: Peter L. Jones Lab, University of Nevada, Reno School of Medicine

This is an additional grant to further the previous study from 2021

The primary therapeutic target in all forms of FSHD is DUX4-fl mRNA and DUX4-FL protein, and animal models of FSHD should be based on DUX4-fl expression. We have previously generated the first viable and fertile transgenic FSHD-like mouse, FLExDUX4, that conditionally expresses DUX4-fl and produces a DUX4-induced FSHD-like phenotype. The goal of this proposal is to use similar technology to generate large animal models of FSHD for preclinical validation of a wide range of potential FSHD therapeutic approaches using minipigs. Successful completion of this project will expedite advancement of therapeutic approaches to the clinic by providing vital tools for assessing preclinical efficacy, safety, toxicology, and dosing in a more human relevant system.

Award Amount: $100,000

2022 – 

Principal Investigator: Dr. Justin Cohen, Yale University

Live cell imaging project which we will test therapeutic compounds on FSHD patient cells that glow during the rare event when DUX4 is turned on. This can determine if a drug is effective in a model that more reflects what happens in patients.

Award Amount: $30,000

2021 – 

Title: Generation of porcine large animal models for FSHD therapeutic development and preclinical testing

Principal Investigator: Peter L. Jones Lab, University of Nevada, Reno School of Medicine

The primary therapeutic target in all forms of FSHD is DUX4-fl mRNA and DUX4-FL protein, and animal models of FSHD should be based on DUX4-fl expression. We have previously generated the first viable and fertile transgenic FSHD-like mouse, FLExDUX4, that conditionally
expresses DUX4-fl and produces a DUX4-induced FSHD-like phenotype. The goal of this proposal is to use similar technology to generate large animal models of FSHD for preclinical validation of a wide range of potential FSHD therapeutic approaches using minipigs. Successful completion of this project will expedite advancement of therapeutic approaches to the clinic by providing vital tools for assessing preclinical efficacy, safety, toxicology, and dosing in a more human relevant system.

Award Amount: $50,000

Title: Translational research and discovering prospective treatment option for FSHD patients. Year 3

Principal Investigator: Dr. Angela Lek, Yale University

This is an additional third year of funding for Dr. Cohen. He is a talented researcher living with FSHD. In part, the grant will further develop his skills at the bench, while concurrently training him in other non-bench options that will allow him to transition to various roles beyond his post-doctoral roles.

Award Amount: $70,000

2020 – 

Title: Molecular Mechanism of p38 Kinase-mediated inhibition of DUX4 Gene in Facioscapulohumeral Muscular Dystrophy

Principal Investigator: Rajanikanth Vangipurapu PhD, Postdoctoral Fellow, Saint Louis University

We have identified a class of transcription factors that are important for DUX4 expression, are known to be regulated by p38 and may link the expression of DUX4 to the p38 signaling cascade. We propose to identify the specific family member, determine where it binds to regulate the DUX4 gene and investigate how its activity is regulated by p38 kinase.

Award Amount: $130,465 over 2 years (Co-Funded with Friends of FSH Research)

Title: Deciphering the Role of Aberrant Protein Synthesis in FSHD

Principal Investigator: Sujatha Jagannathan PhD, University of Colorado, Anschutz Medical Campus

When healthy muscle cells grown in the laboratory are forced to make the FSHD-causing protein DUX4, they die catastrophically. Studying these dying cells can offer a glimpse into the molecular events set in motion by DUX4 that culminate in cell death. Using engineered muscle cells that express DUX4 synchronously upon addition of a small molecule inducer, we propose to study the downstream consequences DUX4-
mediated inhibition of an essential RNA quality control mechanism in the cell called NMD. Our hypothesis is that the translation of defective RNAs stabilized by DUX4 could flood the cell with defective and toxic protein products.

Award Amount: $197,753 over 2 years (Co-funded with Friends of FSH research)

2019 – 

Title: Drugs targeting DUX4 expression in FSHD

Principal Investigator: Dr. Fran Sverdrup, St. Louis University

The grant will sponsor a postdoctoral fellow supervised by Dr. Sverdrup.

Award Amount: $62,623

2018 – 

Dr. Peter L. Jones is the Mick Hitchcock, PhD, Endowed Chair in Medical Biochemistry and Associate Professor in Pharmacology at the University of Nevada, Reno School of Medicine.

BioPredict Inc. is a US biotechnology company focused on the development and application of novel drug discovery computational technologies.

The Carrino Foundation connected Dr. Peter Jones with BioPredict. The collaboration has identified new epigenetic regulators of DUX4 expression, which represent promising new drug targets for FSHD. This proposal aims to develop specific and effective small molecule inhibitors to these targets, in order to correct the underlying epigenetic defect in this disease.

Award Amount: $75,000

Title: Translational research and discovering prospective treatment option for FSHD patients. (Year 1 of 2)

Principal Investigator: Dr. Angela Lek, Yale University

Post Doc: Justin Cohen, PhD

Dr. Cohen is a talented researcher living with FSHD. In part, the grant will further develop his skills at the bench, while concurrently training him in other non-bench options that will allow him to transition to various roles beyond his post-doctoral roles.

Award Amount: $180,000 over 2 years

Title: Developing a novel FSHD therapy using N.A.P.A.L.M., a novel nucleic acid-peptide conjugate designed to destroy the DUX4 protein

Principal Investigator: Scott Q. Harper, PhD

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $85,000

Title: Regulation and activity of the DUX4 transcription factor

Principal Investigators: Dr. Stephen Tapscott and Dr. Amy Campbell

Fred Hutchinson Cancer Research Center

Award Amount: $325,950 over 4 years*

*Co-Funded with Friends of FSH Research

Title: Developing a muscle-specific DUX4 inhibition system for FSHD therapy

Principal Investigator: Jocelyn O. Eidahl, Ph.D.

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $71,613*

*Co-Funded with Friends of FSH Research

2017 – 

Title: Developing a muscle-specific DUX4 inhibition system for FSHD therapy

Principal Investigator: Jocelyn O. Eidahl, Ph.D.

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $78,658*

*Co-Funded with Friends of FSH Research

2016 – 

Title: Developing a muscle-specific DUX4 inhibition system for FSHD therapy

Principal Investigator: Scott Q. Harper, PhD

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $85,000

2015 – 

Title: Developing a muscle-specific DUX4 inhibition system for FSHD therapy

Principal Investigator: Scott Q. Harper, PhD

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $75,625

2014 –

Title: An FSHD Model for therapeutic development, Renewal for Year 2

Principal Investigator: Peter L. Jones

Department of Cell and Developmental Biology, University of Massachusetts Medical School

Award Amount: $107,777

Title: Developing a muscle-specific DUX4 inhibition system for FSHD therapy

Principal Investigator: Scott Q. Harper, PhD

Department of Pediatrics, The Ohio State University and Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital

Columbus, OH

Award Amount: $49,473

2013 – 

Title: An FSHD Model for therapeutic development

Principal Investigator: Peter L. Jones

Department of Cell and Developmental Biology, University of Massachusetts Medical School

Award Amount: $25,000