Understanding nerve damage in hereditary spastic paraplegia
Official title: Mechanisms Underlying Axonopathy in Hereditary Spastic Paraplegia
Funded at University of Wisconsin-Madison · NIH-11324245 · Data updated 2026-11-12
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.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Wisconsin-Madison NIH-funded |
| Lab location | 1 site (Madison, United States) |
| Project start | May 1, 2022 |
| Project end | March 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $375,430 |
| NIH project number | 5R01NS124165-05 |
| Project ID | NIH-11324245 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with a clinical diagnosis of hereditary spastic paraplegia or known pathogenic mutations in genes like SPG4, SPG57, or SPG80 would be the most relevant to contribute samples or join related future studies.
✕Less likely to help
Individuals without HSP or with unrelated causes of spasticity are unlikely to directly benefit from the findings of this genetically focused project.
What this research studies
The team creates rat models carrying the same HSP gene mutations seen in patients and grows neurons from patient-derived induced pluripotent stem cells (iPSCs). They use CRISPR genome editing to reproduce specific pathological variants and compare early- and late-onset forms of disease. High-resolution live confocal imaging and electron tomography let them watch axons and cellular structures break down over time. The goal is to link specific molecular problems to the progressive gait problems and paralysis patients experience and to use these models as platforms for finding new therapies.
Why it matters
Potential benefit: If successful, this work could identify cellular targets that lead to new treatments to slow or prevent paralysis in hereditary spastic paraplegia.
How similar studies have gone: Previous rodent and iPSC models have replicated many HSP features, but applying high-resolution live imaging and electron tomography to define the exact mechanisms of axon degeneration is relatively new.
Where this research is happening
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University of Wisconsin-Madison
Madison, United States Active
Researchers
- Principal investigator: Audhya, Anjon — University of Wisconsin-Madison
- Study coordinator: Audhya, Anjon
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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Understanding how full-length spastin works and its role in hereditary spastic paraplegia
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.
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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 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.