Neuronal Cholesterol Enzyme CYP46A1 and Rett Syndrome biology
Official title: Neuronal Cholesterol Homeostasis Enzyme CYP46A1 in the Pathophysiology of Rett Syndrome
Funded at Syracuse University · NIH-11465463 · Data updated 2026-11-12
A study in Rett syndrome explores whether tweaking a brain cholesterol enzyme called CYP46A1 could help with the disease by affecting brain pathways involved in Rett.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Syracuse University NIH-funded |
| Lab location | 1 site (Syracuse, United States) |
| Project start | August 15, 2026 |
| Project end | July 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $224,250 |
| NIH project number | 1R21NS147521-01A1 |
| Project ID | NIH-11465463 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with Rett syndrome or MECP2-related conditions, or those contributing samples in future translational work, may benefit depending on subsequent clinical steps.
✕Less likely to help
This study is preclinical and may not directly benefit patients in the short term until clinical translation is pursued.
What this research studies
Rett syndrome is a complex brain disorder caused by MECP2 mutations, and this project looks at how a neuron-specific enzyme that controls brain cholesterol (CYP46A1) might influence Rett-related problems. The researchers will examine how altering CYP46A1 activity relates to Rett symptoms and whether vitamin D could modulate this pathway to improve outcomes. The study builds on prior findings that vitamin D can impact multiple brain pathways and that CYP46A1 expression changes in Rett models, with the goal of identifying a feasible therapeutic angle. This work focuses on mechanisms in neurons and may inform future approaches that are safe for humans already approved as therapies.
Why it matters
Potential benefit: If successful, this work could identify a brain-chemical pathway that can be targeted with available or safe interventions to help manage Rett-related symptoms.
How similar studies have gone: Previous work suggests that vitamin D can modulate Rett-related pathways, but direct targeting of CYP46A1 in Rett is a novel but plausible direction.
Where this research is happening
-
Syracuse University
Syracuse, United States Active
Researchers
- Principal investigator: Macdonald, Jessica L. — Syracuse University
- Study coordinator: Macdonald, Jessica L.
Related research
Other NIH-funded projects on the same topics.
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Neurophysiological biomarkers to speed Rett syndrome therapies
A study to find measurable brain signals that show whether treatments are helping children with Rett syndrome.
-
MeCP2 reactivation on the inactive X to treat Rett syndrome
This project explores turning on the silent MECP2 gene on the inactive X chromosome to help people with Rett syndrome feel better.
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Glial signaling and breathing in Rett syndrome
Aims to understand how brain support cells (glia) in Rett syndrome affect breathing and whether IGF-1 related signals can improve it.
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Studying how deep brain stimulation helps Rett syndrome in mice
Researchers are testing how deep brain stimulation affects brain cells and memory in a mouse model of Rett syndrome to uncover mechanisms that could guide future therapies.
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Molecular Pathways Behind Rett Syndrome in Humans
A patient-focused look at how changes in the MECP2 gene affect brain function and development in Rett syndrome.
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Understanding Rett Syndrome: How MECP2 Mutations Drive Brain Disease
This grant explores how mutations in MECP2 cause Rett syndrome and aims to uncover the brain changes that lead to intellectual disability in affected individuals.
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.