AAV-MEDIATED GENE THERAPY OF THE MPSII MOUSE MODEL

Children affected by mucopolysaccharidosis type II (MPSII; Hunter syndrome) lack the activity of a particular enzyme that is known as iduronate 2-sulfatase (IDS). They accumulate specific compounds in their body that gradually kill their cells, with the consequent damage of all of their visceral organs. At present, efficient therapies are not available. We have in our laboratory a mouse model of MPSII. We have studied their characteristics and found that these mouse show similar symptoms to humans. A gene therapy approach was initiated to set up an efficient treatment for this disease. The affected mice were injected with viral particles that target the liver. Here they can produced high levels of active IDS that is secreted into their plasma and later taken up by all of the organs in their body. This approach gave important results, as the mice were cured of their visceral defects. Now we plan to determine the lowest dose of viral particles that is sufficient for treatment of these mice. Furthermore, we aim to characterize the defects in the brains of these MPSII mice, and to design an efficient gene therapy approach for their treatment. Finally, our aim is to determine if this gene-delivery approach that we have designed for adult mice is suitable to treat baby MPSII mice. Their liver and muscle will be modified in this way to produce and secrete high amounts of active IDS into the blood, which can again cross-correct the other damaged organs. If successful, this approach should allow the treatment of the disease at a very early stage, and even before the symptoms are manifested.