Could Gene Therapy Help Cure Sickle Cell Disease?

By Dennis Thompson
HealthDay Reporter

MONDAY, Dec. 13, 2021 (HealthDay News) — A gene remedy that would present a everlasting remedy for sickle cell illness continues to point out success by way of a 3rd wave of sufferers, researchers report.

The remedy, LentiGlobin, restored regular blood perform in 35 sickle cell sufferers who had the one-time process, in response to medical trial findings printed Dec. 12 within the New England Journal of Medicine.

The sufferers are all now producing secure quantities of regular purple blood cells containing wholesome hemoglobin, stated lead researcher Dr. Julie Kanter, director of the University of Alabama at Birmingham’s Adult Sickle Cell Clinic.

In addition, they haven’t suffered the extreme ache episodes that include sickle cell illness, she stated.

“It’s the start of a brand new life” for these sufferers, Kanter stated.

Around 49 sufferers have been handled with LentiGlobin till now, in response to the gene remedy’s developer, pharmaceutical firm Bluebird Bio.

Sickle cell illness impacts the form of an individual’s purple blood cells. Normally, these cells are disc-shaped and versatile sufficient to maneuver simply by way of blood vessels.

The purple blood cells of an individual with sickle cell illness are crescent-shaped, resembling a sickle. The cells are stiff and sticky, and trigger ache episodes and different well being issues once they clump collectively in several elements of the physique.

These issues are brought on by a substance known as hemoglobin, which is the a part of a purple blood cell that carries oxygen to tissues all through your physique, Kanter defined. A defective gene causes the physique to provide faulty hemoglobin that distorts the form of the blood cells.

“They nonetheless carry oxygen, however they do not maintain the oxygen as properly, and when the cells drop off oxygen the hemoglobin intertwines with its fellow hemoglobins, inflicting the cell to be misshapen and sickled,” Kanter stated.

In this remedy, stem cells are faraway from an individual’s blood-producing bone marrow. Lab technicians expose them to a virus that inserts into them a wholesome copy of the defective hemoglobin gene.

While this takes place, the affected person’s remaining bone marrow is killed off with chemotherapy. The lab-repaired stem cells are then implanted and begin producing wholesome hemoglobin.

“This is form of like doing a bone marrow transplant into your self,” stated Dr. Lewis Hsu, chief medical officer of the Sickle Cell Disease Association of America.

The medical trial replace printed within the NEJM — and offered concurrently at a gathering of the American Society of Hematology, in Atlanta — stated that as a lot as three years previous their therapy, the third wave of LentiGlobin sufferers displayed a sequence of promising indicators indicating a everlasting remedy:

• Almost all their purple blood cells comprise wholesome hemoglobin, fairly than the defective hemoglobin brought on by faulty genes.
• Their purple blood cells are breaking down at a standard charge; sickle cell illness often causes the cells to interrupt down a lot quicker.
• None had skilled extreme ache episodes that landed them within the emergency division; previous to therapy, they usually suffered greater than three a 12 months.

“This is an amazing enchancment, as many of those people had a number of occasions previous to this transplant the place they had been within the hospital or within the emergency division due to these horrible painful occasions,” Kanter stated.

The researchers proceed to trace sufferers for one ultimate indication of a real remedy — long-term well being of their organs. Sickle cell places stress on the kidneys, lungs, coronary heart and mind, and it is hoped that the LentiGlobin therapy will forestall the organ injury brought on by the illness.

“We simply do not know that but as a result of it takes a very long time to collect that data, nevertheless it’s actually thrilling,” Kanter stated.

The sickle cell illness group has been pulling for the success of LentiGlobin, Hsu stated.

“This is the gene remedy that is been out the longest now for sickle cell,” he stated.

However, Hsu famous that there are security considerations that also must be ironed out with the process.

One of the primary sufferers handled with LentiGlobin developed leukemia about 5 years later and died, Hsu stated.

A second paper printed within the new NEJM shed some mild on her loss of life, explaining that LentiGlobin itself didn’t instantly trigger her leukemia. Instead, it seems to have been induced indirectly by her sickle cell illness together with the transplant process.

Leukemia has been a priority with this remedy, Kanter stated.

“We fear that when the virus places the brand new gene in, it places it someplace it is not presupposed to,” she stated. “It did not try this. That shouldn’t be what occurred. It wasn’t in any respect associated to LentiGlobin itself, nevertheless it was associated to the method of the stem cell transplant, we expect.”

Since that first wave of sufferers, Kanter stated, researchers have modified the best way stem cells are collected and the best way the virus is launched to them.

The researchers hope the adjustments will forestall the method that induced the leukemia. “We hope we have prevented that further stress on the bone marrow,” Kanter stated.

Combined, the 2 papers are “displaying actually good outcomes.” Hsu stated the factor now could be to determine what dangers the gene remedy could pose.

“The undeniable fact that it is nonetheless not defined nonetheless makes us take a look at the success of this and understand that there is nonetheless dangers in gene remedy, there’s nonetheless dangers in medical trials,” he added.

Kanter expects that LentiGlobin will transfer to U.S. Food and Drug Administration approval throughout the subsequent couple of years. The remedy doubtless shall be dear, factoring in the price of the remedy, the chemotherapy and the weeks spent in a hospital.

“Unfortunately, I believe for a very long time it is going to be very costly. The subsequent steps of this are how do you make it simpler and cheaper and extra obtainable,” Kanter stated.

More data

The U.S. National Institutes of Health has extra about sickle cell illness.

SOURCES: Julie Kanter, MD, director, Adult Sickle Cell Clinic, and affiliate professor, division of hematology and oncology, University of Alabama at Birmingham; Lewis Hsu, MD, PhD, chief medical officer, Sickle Cell Disease Association of America, Hanover, Md.; New England Journal of Medicine, Dec. 12, 2021, on-line; presentation, American Society of Hematology assembly, Atlanta, Dec. 12, 2021