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
SEP 20, 2020
Drug Discovery & Development
New Drug Combo Prolongs Survival with Advanced Kidney Cancer
SEP 20, 2020
New Drug Combo Prolongs Survival with Advanced Kidney Cancer
Biopharmaceutical company Bristol-Myers Squibb has found that a new drug combination can reduce death rates among those ...
SEP 21, 2020
Drug Discovery & Development
Metformin Does Not Work in All Type 2 Diabetics
SEP 21, 2020
Metformin Does Not Work in All Type 2 Diabetics
Although metformin is the first-line drug for type-2 diabetics, research shows that it is not always effective for all t ...
OCT 06, 2020
Cannabis Sciences
Cannabis Use May Reduce Cancer Risk by 10%
OCT 06, 2020
Cannabis Use May Reduce Cancer Risk by 10%
A recent meta-analysis of 34 studies found that cannabis use may decrease one’s risk of developing certain kinds o ...
NOV 01, 2020
Cannabis Sciences
Can Cannabis Treat ALS?
NOV 01, 2020
Can Cannabis Treat ALS?
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative illness that damages motor neurons and leads to progressive m ...
NOV 06, 2020
Drug Discovery & Development
Anti-depressant Shows Promise in Treating Childhood Cancer
NOV 06, 2020
Anti-depressant Shows Promise in Treating Childhood Cancer
Researchers from Sweden and the US have found that a commonly prescribed antidepressant may help stop the growth of a ca ...
NOV 20, 2020
Drug Discovery & Development
Cat Parasite Gives Clues on New Drug Targets for Schizophrenia
NOV 20, 2020
Cat Parasite Gives Clues on New Drug Targets for Schizophrenia
Researchers from the UK and France have discussed a mechanism of action behind the infamous Toxoplasma gondii  ...
Loading Comments...