Metachromatic Leukodystrophy (MLD) is a rare lysosomal storage disease which is genetic, degenerative, neurometabolic in nature. It is generally inherited from carrier parents and at present doesn’t have any cure. Patients suffering from MLD are deficient in the arylsulfatase-A enzyme, which is responsible for breaking down fatty substances called sulfatides into harmless chemicals. A person with MLD cannot break down these sulfatides, causing them to accumulate in the body. This accumulation causes the destruction of myelin (demyelination), which is the protective covering on the nerve fibers that enables communication between the nerves and the brain.

In terms of disease types, there are four types Metachromatic Leukodystrophy i.e. Infantile, Early Juvenile, Late Juvenile and Adult forms. These forms might affect people at different stages of life. Till date, treatment relating to bone marrow and stem cell transplants have been successful in slowing or stopping MLD in patients. However, in the late infantile phase, which is the most common and most aggressive form of the disease, transplants can generally only happen with younger siblings of patients who have been diagnosed with MLD.

The treatment scenario of Metachromatic Leukodystrophy- apart from stem cell and bone marrow transplants- is not very encouraging as there is no approved treatment for this indication and very few drugs are present in the development pipeline. Only 5 companies are working in drug development for its treatment, providing bleak future for treating this degenerative disease. The pipeline of Metachromatic Leukodystrophy is quite weak at present with only one Phase III drug i.e. GSK-2696274 with GlaxoSmithKline and one drug in Phase II stage with Shire. As Metachromatic Leukodystrophy is a genetic disorder, companies are however intent on exploring technologies related to Gene Therapy, Cell therapy, and Enzyme technology while certain institutions are also working relentlessly towards exploring new treatment scenarios.

Assessing this indication landscape, it can be said that the sphere has a high unmet need for new therapies and therefore needs robust research effort. At present, controlling the expression of malfunctioning gene as well as modulating the activity of ARSA enzyme is the only currently available treatment that can provide some ray of hope for treating this untreated indication while new research output may provide a much-needed boost for patients suffering from this genetic condition.

Insight by:
Anurag Mathur
Senior Associate Analyst