Mucopolysaccharidoses are a group of inherited diseases that result from loss-of-function mutations in those genes that encode enzymes that degrade long-chain sugar molecules. One of these mucopolysaccharidoses, Hurler syndrome, is a consequence of the inability to make a functional version of an enzyme called iduronidase. Without functional iduronidase, cells cannot degrade molecules called glycosaminoglycans (formerly called mucopolysaccharides), which are found in mucus and in fluid around the joints. The concentrations of these glycosaminoglycans increase and damage organs, including the heart. Symptoms can range from mild to severe.
Hurler syndrome is inherited, and both parents must pass the faulty gene to inherit Hurler syndrome.
The symptoms of Hurler syndrome usually appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life. The most common symptoms include abnormal bones in the spine, claw hand, cloudy corneas, deafness, halted growth, heart valve problems, joint disease (including stiffness),
Intellectual disability that gets worse over time, and thick, coarse facial features with a low nasal bridge.
Hurler’s syndrome appears in about 1 in 100,000 live births, and those afflicted with it normally die in their teens.
Treatments for Hurler Syndrome include “enzyme replacement,” which is very expensive. Enzyme replacement therapy utilizes genetic engineering to make large quantities of iduronidase, which is then administered to Hurler Syndrome patients. A second treatment is bone marrow transplantation, but this requires finding a good tissue match.
Sharon Byers from the University of Adelaide, Australia and her colleagues are genetically modifying adult stem cells (mesenchymal stem cells, specifically) to make large quantities of iduronidase. These modified stem cells are then infused into Hurler Syndrome patients. To date, these experimental treatments seem to be providing Hurler Syndrome patients some relief, but it is still early in the trial.
Matilda Jackson, a PhD candidate in Byers lab, described their trial in this manner: “We have turned adult stem cells into little ‘enzyme factories” by coupling them with a virus that makes them pump out high levels of the enzyme.” Matilda Jackson is a member of the School of Molecular and Biochemical Sciences and Adelaide University.
Dr. Jackson continued, “Those stem cells can then be injected into the blood where they move around the body and become liver or bone or brain or other cells and start producing the missing enzyme. They automatically migrate to areas of damage in the affected individual. So far in our laboratory studies we’ve measured improvements in brain function but we’ve yet to complete the analysis to determine if there are improvements in other organs.”
Sharon Byers, an affiliate senior lecturer in the School of Molecular and Biomedical Sciences, explained, “There are two current treatments for Hurler’s Syndrome: costly enzyme replacement therapy or bone marrow transplants which require a perfectly matched donor. And while they bring some improvements,, neither of these treatments prevents damage to the brain and bones because not enough enzyme reaches either of these tissues.”
Dr. Byers continued: “These stem cells, modified so that produce large quantities of the enzyme that people with Hurler’s Syndrome lack, offer great hope for a potential new therapy. If we can help reverse the disease symptoms, we could see these children able to perform normal tasks, giving them a better quality of life and increasing their life span.”