Research on rare diseases has always been not easy. By their very nature – they affect less than 5 in 10 thousand people – there are few patients. Studying them is difficult and setting up clinical trials to test the efficacy of any drugs is complicated, not only due to the reduced availability of patients but also due to the difficulties in attracting sponsors willing to finance the trials. Tay-Sachs disease, a rare genetic-based disease, is no exception, and the results for the first gene therapy for two children with this disease were also achieved thanks to donations from family members of one of the patients involved in the clinical trial.
To tell it, on the pages of The Conversation, is one of the scientists part of the team. His name is Miguel Sena-Esteves and he works at UMass Chan Medical School, where he heads the Translational Institute for Molecular Therapeutics for the development of gene therapies. It is here that he and some colleagues from Auburn University have developed a type of gene therapy suitable for administration to patients with Tay-Sachs.
Towards gene therapy for the most common muscular dystrophy
by Barbara Orrico
The disease – due to gene alterations in the gene for the enzyme hexosaminidase A (HexA), which cause a deficit with consequent accumulation of toxic substances in the brain and neuronal death – exists in different forms. The most common and the most serious is childhood, which affects children from the first months, with significant motor deficits, problems with sight, hearing, cognitive retardation, convulsions, generally leading to death in early childhood. Gene therapy, which aims to correct the genetic defect by administering the outside of the gene for the corrected enzyme, is a viable path for these patients. But it comes up against, among others, one difficulty in particular: to treat the disease it is necessary to bring gene therapy into the brain, and crossing the blood-brain barrier that protects it is not easy. For this, reports Sena-Esteves, the team of researchers developed viral vectors – harmless, they act as ferrymen in the body of the correct gene instructions – and injected them at the level of two distinct regions in the central nervous system, in two small patients. one of seven months and one of two and a half years. In the first, the experts observed an improvement in brain development and the disappearance of seizures up to the age of two, in the second, muscular and visual improvements and also in this case the absence of seizures, up to the age of 5. These results, notes Sena-Esteves, which in the natural course of the disease would be impossible to observe. In both cases, samples from the cerebrospinal fluid confirmed the production of the desired protein after the administration of gene therapy.
Metachromatic leukodystrophy, 29 children treated with gene therapy
by Irma D’Aria
The data reported are only extremely preliminary, especially since in one of the patients, after an initial stabilization, the recovery of the disease was observed. But they show that the path of gene therapy could be feasible for these patients, as the Sena-Esteves team tells in the pages of Nature Medicine, in the official presentation of the results. And it is a path that is worth pursuing, starting with new tests, on more patients, and with higher doses of the therapy, concludes the researcher.