Gurler Syndrome Was Suppressed For The First Time With The Help Of Intrauterine Gene Therapy
Intrauterine gene therapy for the first time suppressed Gurler syndrome in mice, a rare genetic disease that causes many congenital developmental defects to manifest in the first months of life. The description of the study is available in the scientific journal Nature Communications.
"It also turned out that with the help of this procedure, some of the manifestations of the disease can be suppressed even after birth. This gives confidence in the further success of this therapy," said one of the authors of the study, William Peranto from the Children's Hospital of Philadelphia (USA).
Gurler syndrome is a severe hereditary disease. It occurs due to malfunctions in the work of lysosomes – cellular "incinerators." As a result, there are problems in the work of metabolism, which causes severe disorders of intrauterine and postnatal development.
This disease affects about one person out of a hundred thousand, and in most cases, mutations in the IDUA gene are the cause of its appearance. This section of DNA is responsible for the production of one of the enzymes of lysosomes, which is involved in the decomposition of glycosaminoglycans – substances that are part of the secretions of the mucous membranes and intercellular substance of connective tissue.
Peranto and his colleagues have been working for several years on a gene therapy that could correct one of the most common mutations associated with the development of Gurler syndrome. The therapy is based on an adenovirus, inside which scientists have placed a CRISPR/Cas9 genomic editor and a set of RNA "instructions" according to which this system finds and corrects one specific point mutation in the IDUA gene.
Such therapy should be used even during the intrauterine development of children with such a mutation since the first manifestations of Gurler syndrome occur even before the child or cub is born. In addition, the embryo's immunity does not react to adenoviruses as actively as the body of children and adults.
Therefore, biologists tested their therapy on two-week-old embryos of mice whose parents had a mutant version of the IDUA gene. Further observations show that in 15-23% of cases, the virus successfully penetrated the cells of the future liver and heart and replaced the damaged version of the gene with its correct version.
According to scientists, this is quite enough to suppress a significant part of the symptoms of Gurler syndrome, which usually begin to manifest themselves in the first weeks of life of children and mice. In particular, the rodents participating in the experiments did not suffer from heart disorders, which usually cause premature death of carriers of this disease, as well as muscle deformities and other consequences of its development.
Then the scientists tested whether the therapy would improve the condition of young rodents born with Gurler syndrome. It turned out that after the introduction of adenovirus into the body of mice, their health and behavior improved. But in celos, this did not save them from the consequences of the development of the disease.
Now Peranto and his colleagues are working on a new version of gene therapy that could correct mutations not only in heart and liver cells but also in the fetal brain tissues. Its creation will be a big step towards the development of the first full-fledged methods of treating Gurler syndrome, the researchers concluded.