JUL 23, 2018 12:20 PM PDT

Targeting a Protein Kinase in Sickle Cell Disease

WRITTEN BY: Nouran Amin

Searching for a drug that may treat sickle cell disease (SCD) blood disorder researchers identified a protein responsible for regulating the production of hemoglobin present in erythrocytes (red blood cells). The identified protein is a signaling molecule and a kinase known as HRI. HRI was seen to regulate the iron-carrying component of blood, hemoglobin. The results of this study were recently published in the scientific journal, Science.

Performing lab tests on cultured human cells revealed that inhibiting HRI resulted in a reduction of the characteristic sickling properties of SCD that cause a distortion of the red blood cell shape ultimately giving the disease its name. "We have found a protein with activity specifically in red blood cells that could be a 'druggable' target, possibly with a small molecule -- a pill that patients could take to treat sickle cell disease," explains study co-leader Gerd A. Blobel, MD, PhD, a scientist at Children's Hospital of Philadelphia (CHOP).

The results of the research study provided evidence of HRI and its role in a unique process known as "hemoglobin switching”; the biochemical transition normally occurring in infants where red blood cells switch from production of a fetal form of hemoglobin to the adult form. Therefore, it is known that the mutation responsible for SCD is actually present in the adult form of hemoglobin, which explains SCD happens to affect patients only after birth.

 

SCD mutation leads to red blood cells becoming abnormally crescent-shaped that clog blood vessels and damages organs; which is painful and life-threatening to affected individuals. The current standard treatment for SCD, prescribed by hematologists, is a hydroxyurea drug that increases fetal hemoglobin. Unfortunately, this treatment is not effective for all patients and so researchers are seeking other options.

Utilizing CRISPR gene-editing techniques, researchers screened a class of domains encompassing protein kinases; enzymes that can be inhibited by a small molecule. This screening method allowed the discovery of HRI, the kinase capable of aiding in the silencing of fetal hemoglobin production in red blood cells. Additionally, these results informed researchers how HRI works to suppress fetal hemoglobin production and how, if inhibiting HRI, can fetal hemoglobin rise.

 

Without altering the viability or maturation of red blood cells, a reduction of “sickling” was achieved on SCD patients, proving that inhibition of HRI function was not a loss. Researchers believe that developing a drug that inhibits HRI might not only be effective for SCD but also as a treatment option for a range of other hemoglobin disorders. "Our long-term goal is to carry out follow-up studies to evaluate whether this approach improves clinical outcomes in patients," said Blobel. "At this point, our results suggest that HRI is a potential target for a new treatment for disorders of hemoglobin."

Source: Children's Hospital of Philadelphia, Science  

About the Author
  • Nouran earned her BS and MS in Biology at IUPUI and currently shares her love of science by teaching. She enjoys writing on various topics as well including science & medicine, global health, and conservation biology. She hopes through her writing she can make science more engaging and communicable to the general public.
You May Also Like
JAN 20, 2020
Cancer
JAN 20, 2020
Did you know these non-cancer drugs can also fight cancer?
A study from MIT. Harvard and the Dana-Farber Cancer Institute has concluded that almost 50 existing non-oncological drugs have anti-cancer properties capa...
FEB 08, 2020
Cancer
FEB 08, 2020
Magic mushrooms help cancer patients' depression
A follow-up to a study originally published in the Journal of Psychopharmacology in 2016 reports the long-term benefits of a one-time, single-dose tre...
FEB 21, 2020
Drug Discovery & Development
FEB 21, 2020
Why is it so Difficult to Develop a Vaccine for Coronavirus?
As of February 21st, 2,250 have died worldwide from Coronavirus, while 18,862 have recovered and 55,703 are currently infected. Having made top news storie...
FEB 21, 2020
Drug Discovery & Development
FEB 21, 2020
New Antibiotics Found Using AI Technology
Using AI, researchers at MIT have found a powerful new antibiotic capable of killing some of the most dangerous drug-resistant bacteria known to man. ...
FEB 21, 2020
Drug Discovery & Development
FEB 21, 2020
Healing Bone Fractures
Studies on rats revealed that two existing drugs can boost repair machinery by triggering the release of bone marrow stem cells. Findings were published in...
FEB 28, 2020
Drug Discovery & Development
FEB 28, 2020
How Dietary Supplement Citicoline Improves Memory
For some time now, Citicoline has been known for its ability to improve memory and reduce cognitive decline. A primary ingredient in many pre-made nootropi...
Loading Comments...