Your new post is loading...
A stem-cell-modifying gene therapy has helped six patients with a rare blood disease, X-linked chronic granulomatous disease (X-CGD), the most common form of CGD, a hereditary immune disorder. Of the nine patients who received the gene therapy in a recent clinical trial, six are currently in remission and no longer receiving other treatments.
In this therapy, hematopoietic stem cells are removed from the patient’s bone marrow, genetically modified outside the body, and then reintroduced to the patient, where the modified cells mature into white blood cells that can produce the pathogen-killing compounds known as reactive oxygen species—immune-boosting chemicals that are lacking in untreated CGD patients. The therapy, if it proves to be effective in larger trials, would be an attractive alternative to an existing therapy that relies on bone marrow donations. “With this gene therapy … cells are perfectly matched to the patient,” said Donald B. Kohn, MD, a stem cell researcher at the University of California, Los Angeles (UCLA). “It should be a much safer transplant, without the risks of rejection.”
Kohn is a co-corresponding author of a new article (“Lentiviral gene therapy for X-linked chronic granulomatous disease”) that describes the clinical trial. The article, which appeared January 27 in Nature Medicine, may remind readers of an earlier clinical trial, one that used a similar stem cell gene therapy to effectively cure a form of severe combined immune deficiency (also known as bubble baby disease) in more than 50 babies. “The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months,” the current article noted. “The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment.” People with CGD have a genetic mutation in one of five genes that help white blood cells produce reactive oxygen species to destroy harmful bacteria and fungi that are ingested during phagocytosis. Without this defensive chemical burst, patients with the disease are much more susceptible to infections than most people. The infections can be severe to life-threatening, including infections of the skin or bone and abscesses in organs such as lungs, liver, or brain. X-CGD affects only males and is caused by a mutation in a gene found on the X-chromosome.
Published in Nat. Medicine (27 January 2020):
