Giving children with immunodeficiency a chance to lead a normal life
For children born with a rare immune deficiency called ADA-SCID, day-to-day activities like going to school or playing with friends can lead to dangerous, life-threatening infections. If untreated, ADA-SCID can be fatal within the first two years of life.
But 11-year-old Eliana Nachem of Fredericksburg, Virginia, is starting sixth grade with dreams of becoming an artist. It鈥檚 a remarkably ordinary life that once seemed impossible.
After Eliana was diagnosed with ADA-SCID at 3 months old in 2014, she lived in complete medical isolation. No pets, no contact with the outside world, with HEPA air filters running constantly and all food and toys sterilized.
Facing the choice between bone marrow transplantation and an experimental gene therapy co-developed by UCLA鈥檚 Dr. Donald Kohn, Caroline and her husband, Jeff, carefully researched both options. A phone call from Kohn about compelling new results from another patient proved decisive.
In September 2014, at 10 months old, Eliana received her corrected cells at UCLA. Caroline and Jeff described watching the infusion as their daughter鈥檚 鈥渞ebirth鈥� 鈥� her own genetically modified cells carrying the promise of a normal life.
鈥淚 remember thinking, she鈥檚 born again, and now we just get to watch her grow,鈥� Caroline said.
Severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, is caused by mutations in the ADA gene, which creates an enzyme essential for immune function. For children with the condition, day-to-day activities like going to school or playing with friends can lead to dangerous, life-threatening infections. If untreated, ADA-SCID can be fatal within the first two years of life.
The blood stem cell gene therapy co-developed by Kohn restored immune function in 59 of 62 children with ADA-SCID with no serious complications reported in a recently published long-term study of the patients.
Current standard treatments 鈥� bone marrow transplant from a matched donor or weekly enzyme injections 鈥� come with limitations and potential long-term risks.
The experimental gene therapy offers a new approach. Doctors collect a child鈥檚 blood stem cells, which create all types of blood and immune cells, and use a modified lentivirus to deliver a healthy copy of the ADA gene. Once infused back into the patient, the corrected stem cells begin producing healthy immune cells capable of fighting infections. Development of immune cells starts shortly after the gene-modified stem cells are reinfused, but聽it takes six to 12 months for the immune system to reconstitute to normal levels.
鈥淲hat鈥檚 most remarkable is that everything has been completely stable beyond the initial three-to-six-month recovery period,鈥� said Kohn, a distinguished professor of pediatrics who has been working to develop gene therapies for ADA-SCID and other blood diseases for 40 years.