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An article recently published in Science Daily quotes the results of a study showing a favorable outcome for six out of nine x-linked chronic granulomatous (CGD) patients. The patients were treated with stem cell gene therapy by an international team that included UCLA researchers. The six patients are currently in remission and have discontinued their previous antibiotics.
CGD is a rare blood disease causing infections and shortened lifespan. Previously, the only possibility for remission was a bone marrow transplant. Otherwise, the maintenance regimen involves treating each recurring infection or using preventive antibiotics.
Bone Marrow Transplant
The bone marrow is comprised of blood-forming stem cells that produce white blood cells. If the donor is well matched, then the bone marrow is capable of producing white blood cells that can prevent infection.
A small percentage of patients survive after bone marrow transplants (BMT). The majority seeking a transplant may not be eligible for the transplant because of advanced age or having comorbidities. Also, their doctors may be unable to locate an appropriately matched donor.
Other complications that arise with BMT include the risk of infection, rejection of the transplantation, or graft versus host disease (GVHD).
Acute GVHD occurs when the patient’s immune system attacks the newly transplanted foreign bone marrow. This may occur in up to eighty percent of transplant patients. Anti-rejection drugs are administered for six to twelve months to prevent GVHD. Over ten percent of these patients do not survive.
Our systems contain five genes that employ a group of chemicals to assist white blood cells in the destruction of fungus and bacteria. If one of these cells have a genetic mutation, then patients become more vulnerable to infections. CGD patients have that one genetic mutation. It is classified as a genetic immunodeficiency disorder.
X-CGD is a common form of CGD affecting the X-chromosome. It affects only males. Infections range from being severe to being life-threatening. Abscesses may appear in the liver, brain or lungs. Infections may occur in the bone or skin.
About the Study
Dr. Donald Kohn is a member of the Broad Center at UCLA and senior author of the newly published paper on CGD in the journal Nature Medicine.
Dr. Kohn joined collaborators in the United Kingdom, France, the NIH in the U.S. and associates at Boston Children’s Hospital.
Dr. Kohn explained that the new gene therapy eliminated one of the complications of bone marrow transplant by using the patient’s own stem cells for the transplant rather than using cells from a donor.
In this way the cells will be perfectly matched and eliminate the risk of rejection.
About the Stem Cell Gene Therapy
A team in London, England collaborated with Dr. Kohn on the X-CGD viral delivery system. Patients ranged from age two to age 27. Four patients were treated at the London facility and five patients were treated in the United States.
The procedure required the blood-forming stem cells to be removed from the CGD patients. The cells were modified in the laboratory and the genetic mutations were corrected.
Once modified, the now healthy stem cells produced white blood cells which contained the missing group of chemicals. The patients then received their modified cells back again through transplantation.
Although this procedure is new for X-CGD patients, Dr. Kohn is credited with pioneering a cure for a type of combined immune deficiency in over fifty cases called the bubble baby disease. There he used a very similar stem cell gene therapy approach.
Two patients in the new gene therapy died within the first three months of treatment. The deaths were reported to be due to infections they were experiencing prior to entering the study.
Seven of the patients who survived the gene therapy were followed for twelve to thirty-six months. All seven patients were free of the CGD-related infection. Six out of the seven patients discontinued the preventive antibiotics that they were taking prior to entering the study.
Dr. Kohn said that not one of the patients had the usual complications that accompany donor cell transplants. He added that the results were as good or even better than those that resulted from donor transplants.
Since the new paper was written, four more patients were treated and have been free of CGD-related symptoms. Also, there have been no further complications.
About the Company
Dr. Kohn is the co-founder of the biotechnology company, Orchard Therapeutics. The company acquired the rights to the X-CGD gene therapy through Genethon. Orchard is working with U.S. and European regulators in an effort to put forth a larger study. According to Dr. Kohn, the company intends to eventually submit an application for approval to market the treatment.
Dr. Kohn and his associates intend to develop similar therapies to treat other types of CGD. These four mutations affect the immune function in a similar manner as X-CGD.
In thinking beyond CGD, Dr. Kohn spoke of other diseases that could be treated in a similar manner as they are also caused by proteins that are absent in white blood cells.
What are your thoughts about this new type of stem cell transplantation that does not require a donor?