SJ-20-0030 – Inhibiting Mir-451 to Treat Beta-Thalassemia

  • Genetic disruption of the red cell expressed microRNA locus miR144/451 causes a dramatic reduction in the severity of beta thalassemia.
  • miR451 acts through a biochemical signaling cascade to inhibit the activity of the autophagy protein ULK1
  • Reduces the severity of beta thalassemia by degrading toxic free alpha globin.

Abstract

There are currently poor drug choices to treat beta thalassemia, a chronic, often debilitating form of genetic anemia that is very common in some parts of the world. New treatments might be achieved using “antagomirs” (oligonucleotides that interfere with the functions of natural microRNAs). Researchers at St. Jude discovered that genetic disruption of the red cell expressed microRNA locus miR144/451 causes a dramatic reduction in the severity of beta thalassemia. They believe that miR451 acts through a biochemical signaling cascade to inhibit the activity of the autophagy protein ULK1, which we recently showed to reduce the severity of beta thalassemia by degrading toxic free alpha globin. Lechauve et al, “The autophagy-activating kinase ULK1 mediates clearance of free alpha-globin in beta-thalassemia,” Sci. Transl. Med., 11 (506), eaav4881, 2019. DOI: 10.1126/scitranslmed.aav4881 https://www.science.org/doi/10.1126/scitranslmed.aav4881 More information is available under a confidentiality agreement.

Advantages

There are currently poor drug choices to treat beta thalassemia, a chronic, often debilitating form of genetic anemia that is very common in some parts of the world. New treatments might be achieved using “antagomirs” (oligonucleotides that interfere with the functions of natural microRNAs).

Potential Applications

Researchers at St. Jude discovered that genetic disruption of the red cell expressed microRNA locus miR144/451 causes a dramatic reduction in the severity of beta thalassemia. They believe that miR451 acts through a biochemical signaling cascade to inhibit the activity of the autophagy protein ULK1, which we recently showed to reduce the severity of beta thalassemia by degrading toxic free alpha globin.

Contact Information

Name: Scott Elmer

Email: scott.elmer@stjude.org

Phone: 901-595-2756