Dr Ewelina Mamcarz, from the St June Department of Bone Marrow Transplantation and Cellular Therapy, said: "These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and lead normal lives".
Infants born with an extremely rare, life-threatening genetic disorder sometimes known as "bubble boy" disease have been effectively cured thanks to a gene therapy developed by United States scientists.
The therapy worked well enough that four of the babies were eventually able to stop getting antibody infusions, which doctors often use to boost immunity. If untreated, the disease is fatal, usually within the first year or two of life.
Ten infants have received the experimental therapy. The treatment was pioneered by a St. Jude doctor who recently died, Brian Sorrentino. He is the senior author and died after the manuscript was submitted for publication.
UCSF played an instrumental role in the St. Jude protocol by including targeted dosing of busulfan, a chemotherapy agent commonly used in bone marrow transplantation to make space in the marrow for donor stem cells to grow.
The trial involved harvesting blood stem cells from the bone marrow of eight infants newly diagnosed with SCID-X1.
New-borns with X-SCID have a mutation in a gene called IL2RG, which encodes for a protein needed for the growth and maturation of lymphocytes and normal immune system function.
Also, it's another respect in which gene therapy could hold an advantage over bone marrow transplant from a matched donor, added Sullivan.
"The hallmark of this disease is infection", and all the patients treated presented with severe, life-threatening disease, she noted.
This process is less likely to cure the bubble boy disease, and is more likely to cause serious side effects as a result of treatment.
With this in mind, the researchers at St. Jude turned to gene therapy - an experimental technique whereby a reengineered virus is used as a vehicle "to introduce a normal copy of the mutated gene into patients' blood stem cells", said Dr. Steven Gottschalk, a co-author of the study from the same department at St. Jude as Mamcarz. The cells were then frozen and underwent quality testing.
Doctors are still monitoring the eight initial patients, who each received the treatment between six months and two years ago and are all seeing positive ongoing results with no severe, negative side effects thus far, the Associated Press reports.
Patients with infections prior to gene therapy have recovered. All are developing and growing normally. The new approach appears safer and more effective than previously tested gene-therapy strategies for X-SCID.
"There remains a theoretical risk but so far with this type of vector (i.e., self-inactivating, or SIN, configured vector), no leukemias have been observed in any of the current HIV-based lentiviral vector studies including in patients with hemoglobinopathies and other diseases such as adrenoleukodystrophy or metachromatic leukodystrophy", commented Hans-Peter Kiem, MD, PhD, director of the stem cell and gene therapy program at the University of Washington in Seattle. In these earlier studies, gene therapy restored T cell function but did not fully restore the function of other key immune cells, including B cells and NK cells.
This new therapy uses a genetically altered virus to infect stem cells in bone marrow collected from the babies.
Once the genes had been delivered, the modified HIV viruses self-destructed inside the patient's blood.
"Past gene therapy efforts did not have these insulators which inadvertently caused leukaemia by activating the genes next to the inserted vector", Professor Gottschalk said.
Vector production and gene therapy treatment were streamlined using a stable producer cell line and cryopreservation. Both are important steps for expanding access to treatment and commercializing production.
Reference: E Mamcarz et al.
The research was funded in part by the California Institute of Regenerative Medicine (CLIN2-09504); grants (HL053749, AI00988, AI082973, CA21765) from the National Institutes of Health; the Assisi Foundation of Memphis; and ALSAC, the fundraising and awareness organization of St. Jude.