Clearing excess alpha-globin to help people with beta-thalassemia
ULK-mediated autophagy of α-globin in ß-thalassemia
['FUNDING_R01'] · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · NIH-11125822
This research looks at whether boosting a cell 'self-cleaning' pathway (ULK1-driven autophagy) can remove toxic excess alpha-globin and help people with beta-thalassemia.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | ST. JUDE CHILDREN'S RESEARCH HOSPITAL (nih funded) |
| Locations | 1 site (MEMPHIS, UNITED STATES) |
| Trial ID | NIH-11125822 on ClinicalTrials.gov |
What this research studies
Researchers are exploring how cells normally clear excess alpha-globin and whether enhancing that cleanup can reduce the damage that causes anemia in beta-thalassemia. In the lab they use mouse models that mimic human beta-thalassemia and cellular experiments to test the role of the ULK1 autophagy pathway and its regulation by mTORC1 and AMPK. They have tested drugs (for example rapamycin) that turn on this clearance pathway to see if it lowers immature red blood cell death, hemolysis, and anemia in preclinical models. If these approaches work in the lab, the team hopes to move toward treatments that could reduce transfusion needs or improve blood production in patients.
Who could benefit from this research
Good fit: People with beta-thalassemia caused by HBB mutations—including those who are transfusion-dependent or non-transfusion-dependent—would be the most relevant candidates for related future trials or sample donation.
Not a fit: Patients whose anemia is due to other causes (for example sickle cell disease or non-hemoglobinopathy disorders) or those with irreversible organ damage from long-standing iron overload may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could reduce toxic alpha-globin, improve red blood cell production, and lower anemia and transfusion needs for people with beta-thalassemia.
How similar studies have performed: Preclinical work in validated mouse models has shown that inhibiting mTORC1 (for example with rapamycin) can stimulate ULK1-dependent autophagy of alpha-globin and reduce ineffective erythropoiesis, but human clinical use of this exact strategy has not been established.
Where this research is happening
MEMPHIS, UNITED STATES
- ST. JUDE CHILDREN'S RESEARCH HOSPITAL — MEMPHIS, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: WEISS, MITCHELL J — ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- Study coordinator: WEISS, MITCHELL J
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.