Glycans and Lysosomal Storage Diseases
In patients with lysosomal storage diseases, genetically-caused enzyme deficiencies result in fragments of undigested glycans accumulating in the lysosomes of cells, producing cell, tissue, and organ dysfunction. The family of lysosomal storage diseases includes approximately forty inherited diseases such as Tay Sachs disease, Metachromatic Leukodystrophy, Fabry disease, and the Mucopolysaccharidoses (MPS). The progressive clinical course can include mobility problems, cardiovascular and respiratory complications, facial abnormalities, hearing and vision loss, profound mental retardation, spinal cord compression, and other serious symptoms with often fatal consequences.
For some lysosomal storage diseases, existing therapies (enzyme replacement therapy) have demonstrated clinical benefit. However, intravenously infused enzymes do not cross the blood-brain-barrier and therefore cannot prevent the severe neurological decline associated with many lysosomal storage diseases. In addition to neurological decline, patients can continue to experience other debilitating and sometimes fatal symptoms due to poor tissue penetration, immune tolerance, and other limitations of existing treatments. As a result, novel approaches are required to reduce the severe morbidity and mortality associated with these diseases.