Oral protein-targeting drugs to raise fetal hemoglobin for sickle cell disease

Targeted protein degraders for the treatment of b-hemoglobinopathies

NIH-funded research Yale University · NIH-11252565

Testing new oral medicines that remove proteins blocking fetal hemoglobin to help adults with sickle cell disease reduce red blood cell sickling.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionYale University NIH-funded
Lab location1 site (New Haven, United States)
Project IDNIH-11252565 on NIH RePORTER

What this research studies

This project aims to create oral small-molecule drugs (protein degraders) that target two proteins that normally keep fetal hemoglobin switched off. Researchers will test these compounds in lab-grown human blood cells and in animal models to see whether fetal hemoglobin (HbF) levels go up and sickling goes down. The teams will optimize the compounds for oral availability and study safety, bioavailability, and dosing in preclinical assays. If promising, they plan steps to move the best candidates toward clinical testing in people.

Who could benefit from this research

Good fit: Adults aged 21 and older with sickle cell disease who still experience sickling or painful crises despite current treatments are the likely candidates.

Not a fit: People under 21, those with other types of hemoglobin disorders not driven by fetal hemoglobin suppression, or patients already cured by transplant or gene therapy are unlikely to benefit from this specific work.

Why it matters

Potential benefit: If successful, these oral drugs could raise fetal hemoglobin to reduce red blood cell sickling and painful crises, offering a less invasive and more affordable option than gene therapy.

How similar studies have performed: Protein degraders are a new class of drugs with early successes in other diseases, but using them to boost fetal hemoglobin for sickle cell disease is largely novel and currently supported mainly by preclinical data.

Where this research is happening

New Haven, 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.
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.