Breakthrough gene therapy gives hope to Artemis-SCID

Ten young children all under the age of 5, born with an immunodeficiency disorder Artemis-SCID, have been able to resume a normal life, thanks to a new gene therapy that allows babies diagnosed with their own cells to be treated, an important step since the disease is normally treated by transplanting bone marrow from a donor.

A revolutionary treatment for Artemis-SCID

“Already, their disease course is so much better than with typical treatment,” said Dr. Mort Cowan, professor of pediatrics at UCSF and principal investigator of the trial.

Combined Artemis-Severus immunodeficiency (SCID) is a very rare genetic disease usually treated with a bone marrow transplant from a healthy donor, ideally a compatible sibling. However, the new gene therapy adds a healthy copy of the Artemis gene to marrow stem cells harvested from the baby. Then the corrected stem cells are injected back into their body to try to avoid many of the short and long term complications of standard treatment, including death.

Patients with Artemis-SCID generally respond less well to standard bone marrow transplants. Complications can include bone marrow transplant rejection, graft-versus-host disease, where donor T cells attack recipient tissue. Chronic infections leading to organ damage, stunted growth and premature death are also significant risks.

The Phase I/II trial for the new gene therapy

The therapy, developed at uc san francisco was the subject of a study published in the New England Journal of Medicine.

“The fact that the patients in the trial achieve complete immunity against T cells is exceptional. B-cell recovery takes longer, but so far it appears that patients also have a much better chance of B-cell recovery than they would with a regular bone marrow transplant,” commented the Dr. Jennifer Puck, UCSF professor of pediatrics and co-lead. study investigator.

The first result of the phase I/II trial involved the safe transfusion of genetically corrected cells that would differentiate into white blood cells 42 days after infusion. All 10 patients were safely transfused with their own genetically corrected stem cells which gave rise to corrected peripheral blood cells during this period.

The researchers predicted that Artemis-SCID patients would need less chemotherapy to prepare their marrow for transfusion when their own cells were used, so only 25% of a full dose of busulfan was given.

The second outcome was T cell reconstitution at 12 months, a measure of the strength of the immune system. All 10 were developing their own T-cells and B-cells at 12 weeks, and four of nine (excluding one patient who received a second treatment) achieved full T-cell immune reconstitution at 12 months. The child who required a second corrected bone marrow infusion due to persistent infection with cytomegalovirus before gene therapy is now infection free with good T and B cell immunity.

Four out of nine also achieved full B-cell immunity at 24 months, allowing them to stop immunoglobulin replacement and receive standard childhood vaccinations.

Three other Artemis-SCID patients, who were followed for less than 24 months, had promising B cell development compared to previous results for donor transplant patients.

“Better B-cell immunity could help avoid problems like chronic lung disease that often develops later in childhood for Artemis-SCID patients who receive standard bone marrow transplantation,” Cowan added.

“Achieving less chemotherapy is also a big win, minimizing the harmful side effects of full-dose busulfan in small infants,” Puck concluded.

The children in the trial currently range in age from 18 months to four and a half years; nine were born in the United States and were diagnosed following newborn screening for SCID; one was born in Canada and diagnosed with clinical illness at five months of age. Four patients are of Navajo/Apache Indian descent, where the Artemis-SCID mutation is more common. The median follow-up was 31.2 months. At the time of publication of the study, six patients had been followed for at least 24 months.