Precision Medicine Treatment Used to Cure 95% of Children With Previously Incurable, Deadly Immune Disease

New genetic technology may lead to cures for many genetic diseases, starting with immune system disorders

A new, experimental precision medicine treatment has developed a potential cure for a deadly immune disease that is fatal in the first two years of life if untreated. Severe combined immunodeficiency (SCID) is a rare genetic disorder that causes severe immune system effects and makes children born with this condition severely susceptible to infection.

While more than a dozen genes have been implicated in SCID, more than 80% of SCID infants do not have a family history of the condition, according to the National Institutes of Health (NIH), which funds SCID studies and developed the original newborn screening test.

Treatment for SCID involves recognizing infections as they begin and treating them promptly. SCID is also treated by using a bone marrow transplant, a dangerous and complex procedure. Even if successful, bone marrow transplants can lead to rejection of the transplant, causing long-term health problems and decreasing survival and quality of life. It is believed that those who receive a transplant before the age of 3.5 months are most likely to survive SCID, regardless of the type of stem cell donor used.

Gene Therapy for SCID Instead of Bone Marrow Transplant

Between 2012 and 2017, a team of researchers from University of California, Los Angeles (UCLA) and Great Ormond Street Hospital (GOSH) in London used precision medicine to treat a specific genetic cause of SCID, sometimes referred to as SCID due to adenosine deaminase deficiency, or ADA-SCID. The researchers, co-led by Donald Kohn, MD, of UCLA and Claire Booth, PhD, of GOSH, applied a gene treatment that specifically targeted this unique cause of SCID.

The team enrolled 50 children into their clinical trials and collected blood-forming stem cells from each child. These stem cells, in healthy individuals, would create the immune cells needed to avoid infection and stay healthy.

The researchers used the genetic technologies they had developed to deliver a healthy version of the gene that was defective in these children. The goal was to change the function of these stem cells to create the functions that they were missing. These cells were then returned to the child where they could start producing normal immune system cells if the therapy was effective.

“Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging,” stated Donald Kohn, MD (above), professor of microbiology, immunology, and molecular genetics, and researcher at University of California, Los Angeles (UCLA), who studies precision medicine therapy for severe combined immunodeficiency (SCID). The treatment technology removes the need to find a match donor for bone marrow transplant and could become standard for ADA-SCID. (Photo: UCLA. Photo copyright: Reed Hutchinson 2018)

Restoring immune function is the primary goal for infants with SCID.

“All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems,” Kohn said in a recent interview. “Treatment was successful in all but two of the 50 cases, and both of those children were able to return to current standard-of-care therapies and treatments, with one eventually receiving a bone marrow transplant.”

One-Time Precision Medicine Treatment for Immune System Disorders?

Pediatric immunology specialists and hospitals that treat genetic conditions in infants and children will find it notable that this precision medicine-based approach is a one-time treatment. When successful, it allows children that would have faced a lifetime of medical monitoring and ongoing treatments to achieve a full and complete recovery.

Clinical trials for this research initiative closed enrollment in 2017, but similar research continues for others who could possibly benefit. Most of the children enrolled in the study have gone on to lead normal lives without any serious long-term health problems or need for ongoing treatment, according to the researchers involved.

“If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions,” said Booth, “removing the need to find a matched donor for a bone marrow transplant and the toxic side effects often associated with that treatment.”

While the treatment used by Kohn and Booth’s team only treated a single, rare immune system disorder, this precision medicine technology has countless applications and may allow clinicians to treat a variety of genetic diseases in the future that have previously been considered incurable.

—Caleb Williams

Related Information:

SCID via the National Institutes of Health (NIH)

SCID viaAmerican Academy of Allergy, Asthma and Immunology (AAAAI)

Precision Medicine Therapy Restores Immune Function in Children

Gene therapy offers potential cure to children born without an immune system

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency

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