AsianScientist (Jun. 19, 2017) – Stem cell transplantations for patients with mutations in the STAT1 gene are highly risky but can cure those that survive the treatment. These findings have been published in the Journal of Allergy and Clinical Immunology.
The STAT1 gene plays a vital role in the body’s immune system. Rare mutations can lead to STAT1’s over activation (gain of function, GOF) and autoimmunity where the body starts attacking its own healthy tissues. While the majority of patients afflicted typically show mild to moderate symptoms involving fungal, bacterial, and viral infections, about ten percent of cases are severe and life threatening.
Until now, developing suitable treatments has been challenging. Anti-fungal drugs temporarily treat the symptoms but not the source mutation, and immunosuppressive therapies often do more harm than good by knocking out already overburdened immune systems.
Prior to the present study, only one case of a patient being cured using stem cell transplantation has been confirmed. To investigate the possibility of using stem cell transplantation more widely, an international team of researchers led by Dr. Satoshi Okada at Hiroshima University studied 15 young patients who had undergone the procedure.
The selected patients were sourced via an international appeal to transplant centers and consortiums. Their ages ranged from 13 months to 33 years at the time of treatment. Screening by researchers at Hiroshima university confirmed that the STAT1-GOF mutation was present in each and was the source of their ailments.
Treatment was carried out independently by centers across the world. They used chemotherapy to eradicate the host’s bone marrow, the source of disease-fighting blood cells in a healthy body—and in these patients—the damaging STAT1 mutation.
Healthy stem cell cultures, sourced from donors, were then transplanted into the host, with the aim of reconstituting their bone marrow to a mutation-free disease-fighting state. Sadly, only six patients survived the transplantation. Of these six, however, five were completely cured and disease-free by the end of the study.
“Overall, this result is disappointing; but the fact five patients were cured proves that treatment with stem cells can work, and we now need to learn from these 15 individual cases,” said Okada, who first discovered the STAT1 gain of function mutation in 2011.
The researchers suspect that the type of chemotherapy used and the age of the patients played a role, as younger patients tended to fare much better. They advised that only patients suffering from severe symptoms should be treated with stem cell transplantation, and that lower doses of chemotherapy should be used.
The article can be found at: Leiding et al. (2017) Hematopoietic Stem Cell Transplantation in Patients with Gain of Function STAT1 Mutation.
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Source: Hiroshima University; Photo: Shutterstock.
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