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 enjoys writing on various topics 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
OCT 09, 2018
Drug Discovery
OCT 09, 2018
Weight Loss Drug Reduces Incidence of Diabetes
A clinical trial weight loss drug, by the name of Lorcaserin—manufactured by Eisai Inc., was found to reduce the risk of diabetes by 19 percent in pa...
OCT 09, 2018
Drug Discovery
OCT 09, 2018
'Copper Antibiotic Peptide' Effective in Eradicating Tuberculosis
The bacterium responsible for Tuberculosis has found a way to avoid antibiotics by hiding inside the macrophages which are the specific immune cells that a...
OCT 16, 2018
Drug Discovery
OCT 16, 2018
Immunotherapeutic Targets A Blood-Clotting Protein
Fibrin is a blood protein that normally does not cross to the brain, however, several neurological disorders have a defect in the blood-brain barrier that ...
NOV 21, 2018
Drug Discovery
NOV 21, 2018
Drug Could Seek New Approach For Autoimmunity
From a failed pain drug, a protein called ‘BH4’, was recently discovered to have surprising implications in the treatment of autoimmunity and c...
DEC 26, 2018
Drug Discovery
DEC 26, 2018
Novel Water Approach May Improve Drug Design
An understanding of the basic molecular properties of water greatly influences drug design. But, a significant comprehension of water interactions and its ...
FEB 08, 2019
Drug Discovery
FEB 08, 2019
Drug Combination Generates New Neurons from Neighboring Cells
In a study published in Stem Cell Reports, scientists at Penn State University have developed a drug cocktail that converts neighboring cells—often k...
Loading Comments...