The NOA Project: Collagen VI Myopathies Pilot Grant Programme
THE NOA PROJECT. COLVI- Pilot Grant Program provides a grant up to two years for $50,000.00 (total cost) to support research related to Collagen Type VI Myopathies (COLVI). The number of grants may vary.
Mutations in the COL6A1, COL6A2, and COL6A3 genes can cause the various forms of collagen VI- related myopathy. These genes each provide instructions for making one component of a protein called type VI collagen. Type VI collagen makes up part of the extracellular matrix that surrounds muscle cells. This matrix is an intricate lattice that forms in the space between cells and provides structural support. The extracellular matrix is necessary for cell stability and growth. Research suggests that type VI collagen helps secure and organize the extracellular matrix by linking the matrix to the cells it surrounds. Changes in type VI collagen structure or production lead to an unstable extracellular matrix that is no longer attached to cells. As a result, the stability of the connective tissue surrounding muscle cells progressively declines, which leads to the muscle weakness, contractures, and other signs and symptoms of collagen VI-related myopathy.1
There are no approved disease modifying therapies for Collagen VI Myopathies and limited standard of care consists of Physical Therapy and stretching. Of all the mutations that exist, the most neglected are those leading to premature stop mutations (PTC) that affect about 10% of patients with COLVI- myopathy. Cell and animal model studies have suggested that increasing the production of COLVI improves muscle function. Advancing research in COLVI myopathies will positively impact research for all stop mutations.
We are seeking grant applications that aim to advance the discovery or development of treatments and/or a cure for COL6A2 PTC mutations. We recognize, however, that many gaps exist in the basic understanding of COLVI protein. Therefore, basic science projects that address these gaps are welcome, provided that they are tethered to the development of a potential therapy. While the RFA is broad in scope, priority will be given to grants that cover the following areas:
- Novel therapeutic approaches for Stop Mutations in COLVI Myopathies, including but not limited to techniques in genome editing, Read-through, RNA-based mechanisms, biologics, novel cell-based therapeutics, network modulation, and development of novel therapeutic compounds, including through small molecule repurposing or screening in human cellular systems.
- Targeting. Interstitial fibroblasts have this far shown decreased efficacy in molecular and viral targeting. Research is needed to learn how to transduce and target resident fibroblast in the muscle tissue to potentially develop novel therapies including genetic manipulation.
- Complements, Investigation into other types of collagen or mutations that can help ease the effects of lack of COLVI. (e.g. compensation by editing/manipulating other collagen family members.)
- Unraveling pathways involved in disease to provide deeper understanding, such as protein Translation, downstream effectors and collagen heterotrimer formation, and intracellular signaling. Identifying novel drug targets. Identifying how much COLVI is needed in the Extra Cellular Matrix to create muscle stability.
- Testing new strategies to treat disease or any of its incapacitating consequences (e.g. contractures, muscle strength, respiratory function decline).
- Discovery and validation of Biomarkers (molecular and functional) with the goal to have clinical setting impact. Currently the standard approach for confirming diagnosis is MRI imaging to confirm phenotypic differences from any other neuromuscular disease and show characteristic findings of deregulated Collagen VI. Of particular interest is biomarker discovery that uses minimally invasive testing. (e.g. skin biopsy, blood).
All applicants with a faculty level appointment at an academic institution or a senior scientific position at a non-profit foundation institution or are eligible. Biopharmaceutical companies are eligible to apply as well as contract research organizations that provide services that are aligned to the RFA.
Applicants must first submit a Letter of Interest (LOI) to be reviewed for consideration of a full application submission.
Format for the 1 page LOI:
- Letter Of Interest
PI and CoPIs, and associated institutions or organizations
- Overall Project, Goals and Budget – it must be clearly described why application is responsive to the RFA.
- Brief background
- Specific Aims provided as a brief list
- Requested resources in terms of one to two years of funding. The total award amount is
$50,000 (including direct and indirect costs). It is strongly preferred that the total amount go towards research, nevertheless indirect costs up to a maximum of 10% could be accepted in exceptional cases.
- Please attach a short video (not more than 2 minutes) explaining the project and goals.
- LOI Due Date: Tuesday June 30th 2020, via this email firstname.lastname@example.org
With the title RESPONSE RFA COL6
- Applicants will be notified via email on Wednesday July 15th, with a decision regarding their LOI. If successful the applicant will be invited to submit a full application.