Breakthrough gene therapy gives hope to Artemis-SCID

10 infants under 5 years of age born with an immunodeficiency disorder Artemis SCID, Thanks to a new gene therapy that allows the diagnosed baby to be treated with his own cells, he is able to return to normal life. This is an important milestone as it is usually treated by a bone marrow transplant from a donor.

A Breakthrough Treatment for Artemis-SCID

“Already, their disease course is much better than usual treatment,” said Mort Cowan, Ph.D., professor of pediatrics at the University of California, San Francisco and lead investigator of the trial.

Artemis Severe combination Immunodeficiency (SCID) is a very rare genetic disorder that is usually treated with a bone marrow transplant from a healthy donor, ideally a matched brother or sister. But a new gene therapy adds a healthy copy of the Artemis gene to the baby’s harvested bone marrow stem cells. The modified stem cells are then injected into the body to avoid many of the short- and long-term complications of standard treatment, including death.

Artemis-SCID patients usually do not respond to standard bone marrow transplantation. Complications may include rejection of a bone marrow graft, graft-versus-host disease, in which the donor’s her T cells attack the recipient’s tissue. Chronic infections that lead to organ damage, failure to thrive and premature death are also a major risk.

New gene therapy phase I/II trial

treatment developed in UC San Francisco reported in a study published in New England Journal of Medicine.

“It’s great that the patients in the trial gain full T-cell immunity. B-cell recovery takes time, but so far, patients have had more B-cells than regular bone marrow transplants.” appears to be much more likely to reconstitute ,” commented Jennifer Puck, Ph.D., professor of pediatrics and co-chair at UCSF. research investigator.

Initial results from a Phase I/II trial included safe transfusion of gene-modified cells that differentiate into leukocytes by 42 days post-infusion. All 10 patients were safely transfused with their own genetically modified stem cells that gave rise to modified peripheral blood cells within this time period.

The researchers predicted that Artemis-SCID patients would need less chemotherapy to prepare their bone marrow for transfusion if their own cells were used, so they received 25% of the total dose of busulfan. only was administered.

The second outcome was T cell reconstitution at 12 months, a measure of immune system strength. All 10 had expanded their T- and B-cells by 12 weeks, and 4 of 9 (excluding patients on second treatment) reconstituted full T-cell immunity by 12 months A child who required a second injection of genetically modified bone marrow due to persistent infection Cytomegalovirus Prior to gene therapy, I am now infection-free due to good T- and B-cell immunity.

By 24 months, 4 of 9 had complete B-cell immunity and were able to discontinue immunoglobulin supplementation and receive standard childhood vaccinations.

Three additional Artemis-SCID patients with less than 24 months of follow-up showed promising B-cell development compared with previous results in donor transplant patients.

“Better B-cell immunity could help Artemis-SCID patients who undergo standard bone marrow transplants avoid problems such as chronic lung disease, which often develops later in childhood,” Cowan said. added.

“The success in reducing the amount of chemotherapy used is also a major benefit, minimizing adverse side effects of full-dose busulfan in infants,” Puck concluded.

Children participating in the trial are currently between the ages of 18 months and 4.5 years. Nine were born in the United States and diagnosed after newborn screening for SCID. One was born in Canada and was diagnosed with the clinical disease at 5 months of age. Four patients are of Navajo/Apache Native American descent, where Artemis-SCID mutations are more common. His median follow-up was 31.2 months. At the time of study publication, six patients had been followed for at least 24 months.