A new test allows doctors to diagnose genetic disorders in fetuses early in pregnancy by sequencing small amounts of fetal DNA in the mother's blood. Non-invasive prenatal tests are already available for chromosome disorders such as Down's syndrome. Two years ago, a similar test was developed for recessive single-gene diseases, which occur when someone has two copies of a faulty gene. That test is particularly useful when one or both parents are known to be carriers for inherited diseases such as sickle cell anaemia, haemophilia or cystic fibrosis. Now there is a test that looks at 30 genes associated with dominant genetic diseases, which occur when someone has just one copy of a faulty gene.
In a study published Wednesday by the New England Journal of Medicine, all 10 men given the therapy now make clotting factor in the normal range. Bleeding episodes were reduced from about one a month before gene therapy to less than one a year. Nine of the 10 no longer need clotting factor treatments, and the 10th needs far fewer of them. There were no serious side effects.
Gene Therapy The two most common monogenic diseases, transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD), result from mutations in the hemoglobin β-subunit gene ( HBB ), which is an essential element of adult hemoglobin A (α2b2). Current therapies for TDT and SCD are limited and do not address their underlying causes. Frangoul et al. report the treatment of two patients (one with TDT and the other with SCD) using gene therapy. After myeloablation, the patients were infused with their own hematopoietic stem and progenitor cells subjected to CRISPR-Cas9 gene editing of the erythroid-specific enhancer region of BCL11A. This transcription factor represses the expression of γ-globin, a component of α2γ2 fetal hemoglobin that is known to ameliorate the severity of these disorders. More than a year later, both patients showed sustained engraftment of edited cells in the blood and bone marrow and increased fetal hemoglobin expression, which relieved symptoms and obviated the need for transfusions. N. Engl. J. Med. 10.1056/NEJMoa2031054 (2020).
A TEENAGE boy with an inherited disease that affects millions worldwide seems to have been cured using gene therapy. The treatment appears to have stopped the painful symptoms of sickle cell disease, demonstrating the potential for gene therapy to treat common genetic diseases. "All the blood tests we performed show that the teenager has been cured of sickle cell disease" The idea of gene therapy – using strands of DNA to compensate for a person's malfunctioning genes – is almost three decades old. However, the approach has so far mostly been used to treat very rare diseases (see "Long road to success"). In contrast, sickle cell disease affects 100,000 people in the US alone.