Mutations in a handful of genes can cause severe combined immunodeficiency (SCID), which severely disrupts the body's ability to fight infection. The condition is typically fatal in the first year of life. Artemis-SCID is a rare form of the disorder that is caused by mutations in the DCLRE1C gene, whish encodes for Artemis, an enzyme that is crucial to the functionality of T and B immune cells. Bome marrow transplants from healthy, matched donors (typically close relatives) can sometimes treat SCID, but those transplants do not work very well as treatments for Artemis-SCID. A new therapy aimed to treat kids with the disorder with their own cells. The researchers have reported that a trial of the approach was successful, and has helped ten young children lead more normal lives. The work has been reported in the New England Journal of Medicine.
In this trial, researchers harvested bone marrow from the patients, then used a lentivirus vector to deliver a normal copy of the gene to the patient cells. The gene-edited bone marrow stem cells were then returned to the patients. Within 42 days, the edited, healthy stem cells were producing peripheral blood cells. Twelve weeks after treatment, all ten patients were generating their own functional T and B cells, except one individual, who had to have a second treatment due to a viral infection. Full reconstitution of immunity was restored within a year for four of the nine patients. Three other patients showed great progress compared to bone marrow donation recipients.
All of the children in the trial are now living at home and are able to attend daycare or preschool; they are leading normal lives, said the lead study investigator Mort Cowan, MD, a UCSF pediatrics professor who has treated over 30 Artemis-SCID patients with bone marrow transplants.
“Already, the course of their illness is so much better than with the typical treatment. I’ve never seen results like this in any of the other kids. It’s amazing,” Cowan added.
The first trial volunteer, named HT, experienced a lot of pain in his early life. Shortly after he was born, his condition was identified and he was taken to UCSF for treatment.
“HT was born with Artemis-SCID, but after he went through the clinical trial, he’s living a normal life now,” said his grandmother and caregiver, Laverna Shorty. “He’s not sick anymore. He discarded all of his medication. He’s happy and he’s growing to be a young man.”
Source: UCSF, New England Journal of Medicine
