Sickle Cell Cure – Genetic Engineering Shows The Way

Highlights

• Sickle cell anemia is an inherited disorder that causes defective hemoglobin to be produced in the red blood cells.
• The defective hemoglobin leads to various clinical symptoms, and may reduce life expectancy.
• Presently, stem cell transplant from a healthy donor is the only hope for a cure.
• In this research, scientists have tried to fix the disease-causing defective gene in the patient’s own stem cells, and re-infusing them, paving the way for a possible cure.

Genetic modification of defective stem cells from sickle cell patients can correct the mutation, and lead to the formation of healthy hemoglobin, indicates a recent research from the University of California, Berkeley, UC San Francisco Benioff Children's Hospital Oakland Research Institute (CHORI) and the University of Utah School of Medicine. Aim of the Study
Scientists hope that correcting the mutation in the stem cells of patients suffering from sickle cell disease , and transplanting back into the patient could be a potential cure for the disease.

"We're very excited about the promise of this technology," said Jacob Corn, a senior author on the study at UC Berkeley. "There is still a lot of work to be done before this approach might be used in the clinic, but we're hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease."

The goal of this research is to develop genetic engineering-based technology to correct the disease-causing mutation in the patient's own stem cells, and to ensure that new red blood cells formed thereafter are healthy.

Details of the Research

The team of scientists performed CRISPR-Cas9 gene editing to correct the defective mutated gene in the stem cells of patients suffering from sickle cell anemia. For the first time, they have managed to correct the mutation in enough number of stem cells, that would lead to the production of healthy hemoglobin, not possible earlier, and alleviate the symptoms of the disease.

Initial tests in mice, using the genetically engineered stem cells have shown that they remained for at least four months after transplantation, indicating that the therapy would be long lasting.

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"This is an important advance because for the first time we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia," said co-author Mark Walters, a pediatric hematologist and oncologist and director of UCSF Benioff Oakland's Blood and Marrow Transplantation Program.

About Sickle Cell Anemia
Sickle cell disease is an autosomal recessive genetic disorder in both copies of the gene coding for beta-globin, a protein occurring in hemoglobin, the oxygen-carrying pigment found in red blood cells.

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This genetic defect causes the hemoglobin molecules to stick to each other, deforming the red cells into the typical "sickle" shape. These misshapen cells get clump together within the blood vessels, and block them, causing signs and symptoms of ischemic tissue damage.

Other clinical features include anemia due to a reduced oxygen carrying capacity, pain, organ failure, and importantly a reduced life expectancy.

Sickle cell disease is particularly common in African-Americans and the sub-Saharan African population, and affects millions of people globally. It is estimated that 1 out of every 365 Black or African-American born suffers from sickle cell disease.

Scope of The Research and Future Plans

• The researchers stress that future pre-clinical work would necessitate additional optimizations, large-scale mouse studies and rigorous safety measures in place.
• Corn and his lab have teamed up with Walters, an expert in developing curative therapies for sickle cell disease including bone marrow transplant and gene therapy.
• They hope to begin an early-phase clinical trial to try out this novel treatment within the next five years
• Additionally, other research groups could employ the approach described in this study to develop treatments for other hematological (blood-related) disorders such as β-thalassemia, chronic granulomatous disease, severe combined immunodeficiency (SCID), and other rare conditions like Wiskott-Aldrich syndrome, Fanconi anemia, and also HIV infection

"Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome," Corn said. "It's very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases."

Says co-senior author, Dana Carroll of the University of Utah, who co-developed one of the first genome editing techniques over a decade ago. "It's very gratifying to see gene editing technology being brought to practical applications."

References:

1. How is Sickle Cell Disease Treated? - (https://www.nhlbi.nih.gov/health/health-topics/topics/sca/treatment)
2. Sickle Cell Disease - Data and Statistics - (http://www.cdc.gov/NCBDDD/sicklecell/data.html)

Source-Medindia