Currently, the standards-of-care for patients with Hurler syndrome, or one of the forms of mucopolysacchardiosis type I (MPS I), include enzyme replacement therapy and hematopoietic stem cell transplants. However, Medical XPress shares that a more effective treatment option may be on the horizon: gene therapy.
Hurler Syndrome (MPS IH)
Hurler syndrome (MPS IH) is a rare metabolic disease and the most severe out of the three MPS I subtypes (others are Scheie syndrome or Hunter-Scheie syndrome). IDUA gene mutations cause Hurler syndrome. Because this condition is inherited in an autosomal recessive pattern, patients must inherit one defective gene from each parent. These mutations cause alpha-L-iduronidase deficiencies. Normally, this enzyme helps break down long chains of complex sugars called mucopolysaccharides. Symptoms occur as these sugars accumulate throughout the body. These include:
- Umbilical or inguinal hernia upon birth
- Short, broad hands with curved fingers
- Macrocephaly (abnormally large head size)
- Hydrocephalus (a buildup of fluid in the brain)
- Frequent respiratory infections
- Enlarged tonsils or adenoids
- Joint deformities
- Thickened or dysfunctional heart valves
- Enlarged spleen and liver
- Thick, coarse facial features with a low nasal bridge
- Corneal clouding
- Abnormal spinal bones or spinal curvature
- Progressive intellectual disability and developmental delays
Gene Therapy
To begin, let’s dive into what gene therapy actually is. Gene therapy can replace a disease-causing gene with a healthy copy of that gene; add a modified and beneficial gene to the body; or even inactivate disease-causing genes. To learn more about gene therapy, head here.
Researchers sought to understand whether gene therapy could be a prospective treatment for Hurler syndrome. This is because the current standards-of-care, while helpful, do offer some obstacles. For example, enzyme replacement therapy (ERT) cannot cross the blood-brain barrier. So if complex sugars accumulate in the brain, ERT is not always effective. While stem cell transplantation can provide the missing enzyme into the brain, using donor cells could cause intense immune reactions in patients.
Thus, researchers thought: why not gene therapy? Within their study, researchers evaluated gene therapy in 8 children with Hurler syndrome. The average age of those treated was two. Findings include:
- Gene therapy was shown to be safe and well-tolerated over a 2-year period, highlighting its potential treatment durability.
- After receiving treatment, the patients had 3-12x higher IDUA gene activity. Additionally, abnormal sugar build-up was greatly decreased.
- Those treated in the trial saw improved growth, as well as learning, thinking, and developmental skills.
Ultimately, researchers believe that gene therapy could be a more effective therapeutic option than stem cell transplants. While more research and observation are needed to determine this, this study does highlight potential new avenues for the future of Hurler syndrome treatment.
