Understanding nerve damage in hereditary spastic paraplegia

Mechanisms Underlying Axonopathy in Hereditary Spastic Paraplegia

NIH-funded research University of Wisconsin-Madison · NIH-11324245

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 typeR01 grant
Study typeNIH-funded research
Funding institutionUniversity of Wisconsin-Madison NIH-funded
Lab location1 site (Madison, United States)
Project IDNIH-11324245 on NIH RePORTER

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.

Who could benefit from this research

Good fit: 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.

Not a fit: Individuals without HSP or with unrelated causes of spasticity are unlikely to directly benefit from the findings of this genetically focused project.

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 performed: 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

Madison, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Amyotrophic Lateral Sclerosis Motor Neuron Disease
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.