Applications for collaborative research on Myhre Syndrome (MS)

The Myhre Syndrome Foundation (MSF) was founded in 2019 as a grassroots effort to provide resources and advocacy for Myhre families and support research funding and education within the medical community.

Myhre syndrome (MS) is a rare genetic disorder caused by two loci of missense mutations in the SMAD4 gene, which plays a crucial role in various cellular pathways such as TGF-β, PTH1R, Wnt / Beta-Catenin, Notch, or BMP. Individuals with Myhre syndrome typically exhibit a distinctive and heterogeneous set of features, including short stature, fibrosis leading to hearing loss, gastrointestinal and respiratory pathology, aortopathy, as well as cardiac muscular and skeletal abnormalities, developmental delays, and IDD. 

The foundation has issued an RFP for high-impact research on prime gene editing strategies or cell therapy to address the increase in SMAD4 activity. Proposals will be accepted for Team Science Awards, which are defined as collaborative research amongst investigators with experience in gene-editing strategies or cell therapy in or outside the Myhre syndrome field. 

For multidisciplinary teams of two or more principal investigators (PIs), MS expects to provide up to $ 450,000 over three years per team to undertake projects with a clear potential to lead to gene therapies or cell therapy for MS patients. The objective of this RFP is to identify promising gene and cell therapies that have the potential to dramatically reduce pathologic burden in MS patients. Potential areas of interest include:

Gene editing: MS-identified pathogenic variants are limited to missense single nucleotide mutations SMAD4 I500V/T/M/L and R496C. MS is autosomal dominant, usually de novo, with a gain of function. Haploinsufficiency and loss of function of SMAD4 are highly pathogenic and push for a gene-editing therapeutic approach. Proposals using prime gene editing strategies would be preferred.

Fibrosis cell/gene therapy: Fibroproliferative reactivity is one of the threats and burdens of MS patients, and efficient therapeutic options in anti-fibrosis remain a major challenge for the treatment of MS. Proposals aimed at developing innovative therapeutics, other than the use of small molecules capable of meeting these challenges are of significant interest.

Awards for team science are designed to foster a collaborative research process amongst researchers with complementary expertise and capabilities, who will work together to advance new therapeutic solutions for MS. Teams may consist of investigators from the same institution or different institutions, including international ones. The designated administrative PI is responsible for administrative leadership. All PIs on the team share authority for scientific leadership.

To be eligible, PIs must hold a full-time faculty or industry appointment at the level of assistant professor (or equivalent) or above at an academic, nonprofit research institution or industry organization whose primary mission is medical research within or outside the United States. PIs must be able to show clear evidence of an independent research program. Fellows or those in other training or research support positions are not eligible.

Letters of intent are due July 1, 2024. Upon review, selected applicants will be invited to submit full-length proposal, due September 2, 2024.

For complete program guidelines and application instructions, see the MSF website.