Cara M. Weismann, PhD

Mucopolysaccharidoses (MPSs) are a family of lysosomal storage diseases, each of which is caused by the absence of a critical enzyme needed for normal lysosomal function. These lysosomal enzymes are needed to degrade mucopolysaccharides, now called glycosaminoglycans (GAGs), as well as other cellular debris. These diseases are autosomal recessive, except for mucopolysaccharidosis type II, which is X-linked. Their overall incidence can be as high as 1 in 29,000 live birth and their individual incidence is in the 1 in 50,000 to 1 in 300,000 range. Depending on the enzyme that is mutated and on the type of GAGs that builds up in the cells and connective tissues, MPSs can be multisytemic diseases involving visceral organs, skeleton, eyes, and central nervous system (CNS) such as MPS I and II; or they can be localized, such as MPS IV and VI which are primiarily peripheral disorders, or  MPS III, which affects the CNS. Therapies aim at restoring the defective enzyme in order to decrease the lysosomal storage and restore cell homeostasis and function.  Peripheral organs may be treated by life-long periodical intravenous recombinant enzyme infusion with approved and marketed drugs for MPS I, MPS II, IVa and VI. However these enzymes do not cross the blood-brain-barrier and cannot slow or prevent the cognitive decline that is associated with MPS I, II and III. ODC has a special interest in MPSs that affect the CNS. CNS directed gene therapy is especially promising for the neurogenic MPSs as the bystander effect of enzymatic cross-correction allows broad effect without having to transduce 100 % of cells.

To learn more about gene therapy for MPS I, click here!