Mucopolysaccharidosis I is caused by mutations in the gene for the enzyme alpha-L-iduronidase (IDUA). This enzyme is required for the breakdown of substances called glycosaminoglycans (GAGs) that are by-products of chemical reactions in the body’s cells. In 2018, a team of researchers was able to demonstrate the feasibility of CRISPR gene editing in vivo in mice via intravenous injection. The treatment partially restored IDUA enzyme activity in organs such as the heart, lungs, liver and kidneys, but not in the brain because the blood-brain barrier protects it. However, this is a problem for patients with the severe form of the disease who may develop cognitive decline. The researchers therefore had the idea of going through the nose to reach the olfactory bulb just above. As a result of the experiments, it was finally shown that non-invasive administration of CRISPR reagents via nasal administration allows gene editing and partial restoration of IDUA activity in the brain and improved cognitive function, while biomarkers of the disease in other organs also improved.
