How a BH4 (SPR) gene mutation may cause oxidant-driven brain cell damage linked to cerebral palsy
Ferroptosis in knock-in sepiapterin reductase mutation rabbits
Researchers are testing whether a human SPR gene mutation that lowers BH4 causes a type of oxidant-driven brain cell death linked to cerebral palsy, using gene-edited rabbits to learn about effects relevant to children with motor problems.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Wayne State University NIH-funded |
| Lab location | 1 site (Detroit, United States) |
| Project ID | NIH-11135415 on NIH RePORTER |
What this research studies
The team made rabbits carrying a human SPR (R150G) mutation using CRISPR and will compare them to normal rabbits. They will use a fetal hypoxia-ischemia model that mimics placental insufficiency to produce cerebral palsy-like injury. Researchers will study ferroptosis pathways, the role of BH4 in oxidant-driven cell death, and measure motor and biochemical outcomes. They will also compare effects with antioxidant approaches to see whether blocking this pathway reduces motor deficits.
Who could benefit from this research
Good fit: Children with confirmed sepiapterin reductase deficiency and infants or young children with early-onset cerebral palsy from perinatal hypoxia could be future candidates for trials informed by this research.
Not a fit: Patients whose cerebral palsy stems from non-oxidative causes or adults with long-standing motor impairment are less likely to benefit directly from these preclinical rabbit results.
Why it matters
Potential benefit: If successful, this work could point to new antioxidant or BH4-related treatments to prevent or lessen motor deficits in children with SPR deficiency or forms of cerebral palsy tied to oxidative injury.
How similar studies have performed: Previous animal work shows antioxidants can reduce motor deficits after hypoxic brain injury, but targeting ferroptosis specifically in the context of SPR mutations is a novel approach.
Where this research is happening
Detroit, United States
- Wayne State University — Detroit, United States (Active)
Researchers
- Principal investigator: Tan, Sidhartha — Wayne State University
- Study coordinator: Tan, Sidhartha
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 below.