Restoring protein balance to improve sleep, metabolism, and memory in Down syndrome

Restoration of proteostasis to address co-occurring conditions in Down Syndrome

['FUNDING_R01'] · UNIVERSITY OF PENNSYLVANIA · NIH-11297676

Researchers are trying a safe drug called 4-phenylbutyrate to help people with Down syndrome have better sleep, healthier metabolism, and clearer thinking by fixing how cells handle proteins.

Quick facts

Phase['FUNDING_R01']
Study typeNih_funding
SexAll
SponsorUNIVERSITY OF PENNSYLVANIA (nih funded)
Locations1 site (PHILADELPHIA, UNITED STATES)
Trial IDNIH-11297676 on ClinicalTrials.gov

What this research studies

This project focuses on people with Down syndrome who often have sleep, metabolic, and memory problems as they age. Scientists plan to use the drug 4-phenylbutyrate (PBA), which is already approved for another condition, to reduce stress on cellular protein-folding systems. The work combines lab studies in mice and analyses of human samples, and includes measures of sleep, metabolic health, and cognitive function to see if those areas improve. The goal is to restore normal protein handling in cells (proteostasis) so multiple co-occurring problems may be eased.

Who could benefit from this research

Good fit: Ideal candidates would be individuals with Down syndrome, especially those experiencing sleep disturbances, metabolic issues, or early changes in thinking and memory.

Not a fit: People without Down syndrome, or those with unrelated causes of cognitive or metabolic problems or who cannot take PBA for medical reasons, are unlikely to benefit from this work.

Why it matters

Potential benefit: If successful, this approach could improve sleep and metabolic health and slow memory decline for people with Down syndrome.

How similar studies have performed: Animal studies and some human data support the idea that reducing protein-folding stress can help, and PBA has prior clinical use, but applying it to Down syndrome-related sleep, metabolic, and cognitive problems is a relatively new approach.

Where this research is happening

PHILADELPHIA, 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.

View on NIH RePORTER →

Conditions: Alzheimer disease dementia, Alzheimer syndrome

Last reviewed 2026-05-15 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.