Understanding how full-length spastin works and its role in hereditary spastic paraplegia
Official title: Regulation of full-length spastin and the etiology of Hereditary Spastic Paraplegia
Funded at Yale University · NIH-11437995 · Data updated 2026-11-12
This grant aims to uncover how the spastin protein uses ATP to cut and regrow microtubules, shedding light on the most common inherited cause of a neurodegenerative leg-weakness disorder.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project start | September 1, 2026 |
| Project end | August 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $462,750 |
| NIH project number | 1R21NS150836-01 |
| Project ID | NIH-11437995 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with hereditary spastic paraplegia or related SPAST mutations may benefit from advances driven by this research.
✕Less likely to help
Results may have limited direct benefit for patients without SPAST-related HSP or related neurodegenerative conditions.
What this research studies
Spastin is an enzyme that consumes ATP to remodel the cell's skeleton and is linked to hereditary spastic paraplegia (HSP). The project seeks to purify the full-length spastin protein and study how its two activities—severing microtubules and promoting regrowth—balance to influence neuron structure. By combining biochemical and biophysical approaches, researchers hope to clarify why spastin mutations lead to disease. The findings could reveal targets for therapies that stabilize microtubules in people with HSP. This is a short, focused grant (R21) intended to push forward basic understanding with potential downstream impact on patient care.
Why it matters
Potential benefit: A deeper understanding of spastin could guide future therapies to protect nerves in people with hereditary spastic paraplegia.
How similar studies have gone: Previous work shows that dissecting spastin's activities can illuminate how microtubule dynamics affect neurons, but full-length purification and mechanistic insight remain challenging and potentially novel here.
Where this research is happening
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Yale University
New Haven, United States Active
Researchers
- Principal investigator: Howard, Jonathon — Yale University
- Study coordinator: Howard, Jonathon
Related research
Other NIH-funded projects on the same topics.
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Understanding axon degeneration in hereditary spastic paraplegia and ALS using patient-derived neurons
Aimed at understanding why certain nerve fibers die in hereditary spastic paraplegia and ALS by studying neurons made from patients’ own stem cells.
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Combinatorial Therapy for SPG4 hereditary spastic paraplegia
Aims to test gene-based treatments to help people with SPG4-related hereditary spastic paraplegia manage mobility and related symptoms.
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Finding hidden genetic causes of hereditary spastic paraplegia
Using whole genome sequencing to find genetic causes for people with hereditary spastic paraplegia whose earlier genetic tests came up inconclusive.
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A new antibody-based therapy for SPG4 hereditary spastic paraplegia
A small NIH grant is funding a therapy aimed at reducing mutant M1 spastin protein to help people with SPG4-HSP, a gradual leg-weakening neurodegenerative condition.
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Understanding nerve damage in hereditary spastic paraplegia
Researchers are using genetically modified rats and patient-derived stem cells to learn how gene mutations cause nerve fiber damage in people with hereditary spastic paraplegia.
-
Understanding and treating a genetic condition that affects movement in children
This study is looking at how certain genes affect movement problems in children with hereditary spastic paraplegia and is testing new treatments that might help improve their nerve function and overall health.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.