The clinical trial
In patients with Parkinson’s, melanoma, leukemia, HIV, hemophilia… gene therapy is envisaged as a valid option in more and more diseases. Now, a new clinical trial shows that it could also “safely” correct the immune systems of newborns diagnosed with a rare and life-threatening hereditary disorder: X-linked severe combined immunodeficiency (X-SCID).
At least, it has worked in eight babies affected by this pathology, which is genetically based and very rare (in the US, one in every 58,000 newborns suffers from it).
Their immune systems can’t behave correctly because the immune cells that fight infections don’t develop or function as expected.
“These children are highly susceptible to certain infections, especially those caused by bacteria. If this disorder isn’t treated, it can have a fatal outcome, usually within the first or second year of life,” the authors report in the article, which has just seen the light in The New England Journal of Medicine. In the clinical practice, the only therapeutic option is bone marrow transplantation with a fully compatible donor. However, less than 20% of babies have this possibility and sometimes, “immunity is only partially restored, with some medical complications such as chronic infections.”
With this scenario, although the treatment with gene therapy has been experimental and tested on a small group of patients, the “results offer great hope,” according to the responsible scientists, who explain that the children “experienced substantial improvements in their immune system function and they grew normally during the two years following the treatment.” In other words, this new approach seems “safer and more effective than the gene therapy strategies previously tested for this genetic disorder.”
At this point, Gloria González, director of the Gene Therapy Program at the Applied Medical Research Center (CIMA), explains that in “the first trials conducted many years ago, part of the patients were cured, but others developed leukemia afterwards.” Since then, “new safer vectors have been developed so the risk of activating oncogenes disappears”. Before, gammaretroviruses were used and now lentiviruses are used.
Gene therapy entails modifying these lentiviruses so they act as a vehicle and introduce genetic material into the altered DNA of the patients’ cells. The objective: to correct the genetic errors that cause different diseases.
Given the success achieved with the eight babies, “gene therapy could be an effective treatment option for newborns with this extremely serious condition, especially in those who lack an optimal donor for the transplant. This breakthrough offers the hope of developing a fully functional immune system and the opportunity to live a full and healthy life,” noted Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases (NIAID), a department of the National Institutes of Health (NIH).
PERFORMANCE OF THE TRIAL
Scientists from NIAID and St. Jude Children’s Research Hospital (Tennessee) developed in conjunction an experimental gene therapy that entails inserting a normal copy of the IL2RG gene into the patient’s cells. In this case, they weren’t older than 14 months and they lacked a genetically compatible donor. First, stem cells were extracted from the bone marrow, then a lentivirus designed to safely transport the normal IL2RG gene was introduced into them to finally infuse the genetically modified stem cells into the patients. “When dealing with their own cells, the chances of rejection are reduced to 0”, noted the deputy director of CIMA.
“With the help of a low dose of a chemotherapeutic drug, the introduced cells began to produce new blood cells,” reports the study. Four months later, the number of immune cells reached the appropriate level and the viral and bacterial infections the participants had before the treatment were cured afterwards. This experimental gene therapy “was generally safe,” according to researchers, although some participants experienced the expected side effects, such as low platelet counts after chemo.
These results achieved with the new approach of gene therapy “are unprecedented,” affirmed Harry Malech, Head of Genetic Immunotherapy at the Clinical Immunology and Microbiology Laboratory at NIAID. Gene therapy approaches from previous studies succeeded in restoring the function of T cells, but weren’t able to achieve the full function of other key immune cells, including B cells and NK cells. In the current trial, participants developed NK cells and B cells.
LUNGS WITH EDITED DNA BEFORE BIRTH
Through genetic edition with Crispr technology, a team of researchers has managed to correct the mutation responsible for a serious lung disease that causes death in the first hours after birth. At the moment, it has only been proven in an animal model, but it’s a first indication of the possibilities and hopes that genetic edition in the uterus could offer to treat diseases of this type before the beginning of life. This is reported by an article published in the journal Science Translational Medicine and conducted by scientists at the Children’s Hospital of Philadelphia. “The developing fetus has many innate properties that make it an attractive receptor for edited therapeutic genes,” according to one of authors for the paper, William H. Peranteau. This is especially important in diseases that affect the lungs, “whose function becomes dramatically more important at the time of birth.”
Date: April 18th, 2019
By: Laura Tardón
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