Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON)
About This Grant
Project Summary Mitochondria play a crucial role in maintaining neuronal health and function. Dysfunction of these organelles leads to various neurological diseases. Retinal ganglion cells (RGCs), the primary output neurons in the retina, are particularly vulnerable to mitochondrial damage. The two most common hereditary optic neuropathies characterized by RGC degeneration, Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON), both stem from mitochondrial dysfunctions. ADOA arises from mutations in OPA1, which regulates inner mitochondrial membrane fusion, while LHON is caused by mutations in the complex I subunit genes encoded by the mitochondrial genome. Currently, no effective treatments exist for either condition, underscoring a critical unmet need to unravel the disease mechanisms and develop therapies to safeguard RGCs from degeneration. The project’s significance lies in investigating the role of SARM1, a trigger of neurodegeneration, in mitochondria-induced RGC degeneration. Our lab has built a novel ADOA mouse model carrying the pathogenic Opa1R290Q/+ mutation. This model recapitulates key features of human ADOA, including mitochondrial fragmentation, aberrant glutathione redox, age-related RGC degeneration, and declines in RGC function. We found that knocking out Sarm1 in these ADOA mice nearly completely protects against all the degenerative phenotypes, suggesting that SARM1 activation drives RGC death in ADOA. Given the similarities between ADOA and LHON, we hypothesize that the same mitochondria-SARM1 pathway also contributes to LHON pathology. Therefore, the central hypothesis of the project posits that mitochondria-induced SARM1 activation leads to RGC death in both ADOA and LHON, and inhibiting SARM1 represents a promising therapeutic approach. Aim 1 of the proposal aims to identify specific mitochondrial defects triggering SARM1 activation in OPA1 mutant RGCs, and elucidate the underlying mechanisms. Aim 2 seeks to establish a dominant-negative SARM1-based therapeutic approach in ADOA mice. During the R00 phase in Aim 3, I will characterize a LHON mouse model and examine whether Sarm1 KO provides protective effects. I have assembled an advisory committee to provide conceptual and technical guidance as I pursue this study. Furthermore, I have also formulated a comprehensive training and career development plan to be executed during the grant period. This integrated proposal, encompassing the research plan and mentoring activities, will provide me with a solid foundation to embark on an independent academic career.
Grant Summary
Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) is a NEI - National Eye Institute grant providing up to $133K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $133K
2028-04-30
- 1Confirm your organization is eligible for Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) from NEI - National Eye Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NEI - National Eye Institute before the deadline.
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Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON): Frequently Asked Questions
Who is eligible for the Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON)?
Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) is offered by NEI - National Eye Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) provide?
Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) provides up to $133K per award from NEI - National Eye Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) deadline?
Applications for Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON) are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NEI - National Eye Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON)?
To apply for Targeting SARM1 as a Therapeutic Strategy for Autosomal Dominant Optic Atrophy (ADOA) and Leber Hereditary Optic Neuropathy (LHON), confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NEI - National Eye Institute.