Extensive work in the lab and some encouraging ALD studies provided the basis for this trial. This trial was subsequently terminated before completion. Enzyme replacement therapy (ERT)
(current as of February 2021)
Takeda acquired the MLD ERT from Shire in early 2018 and continues to develop and studying their intrathecal SHP 611 (formerly HGT-1110) ERT [Enzyme Replacement Therapy]. Clinical Trial
A third global trial studying the late infantile form of MLD for 42 patients aged 6 – 72 months launched in April 2019 and was fully recruited in January 2021. This is the first time ERT study sites are open in the US. Clinical trial information & inclusion criteria can be found on the MLD Foundations ERT page and at the Clinical Trials.gov site. Substrate reduction therapy
Biomarin South (formerly Zacharon before being acquired by Biomarin in January 2013) from San Diego had initiated a drug discovery program for MLD. This program is based on using assays which measure sulfatide accumulation in cultured fibroblasts as a means to discover and develop small molecule drugs for MLD. (This approach differs from other approaches which have measured enzyme activity to discover effective drugs.) As of July 2011, Zacharon has begun adapting the assays it developed for other lysosomal storage diseases so that they can be employed to discover and develop drugs for MLD. (current March 2013)
The Cooper Health System (New Jersey) sponsored a clinical trial underway to determine the safety and efficacy of a Vitamin K antagonist (Warfarin) in treating Metachromatic Leukodystrophy (MLD) in 2009.
Generally early-juveniles have motor skill declines as their first symptoms while late-juveniles show cognitive declines first. The adult form commonly begins after age 16 often with an onset in the 4th or 5th decade of life and presents as a psychiatric disorder or progressive dementia. Adult-onset MLD usually progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.Palliative care can help with many of the symptoms and usually improves quality of life and longevity.Carriers have low enzyme levels compared to their family population ("normal" levels vary from family to family) but even low enzyme levels are adequate to process the bodys sulfatide. Causes
MLD is directly caused by a deficiency of the enzyme arylsulfatase A (ARSA) and is characterized by enzyme activity in leukocytes that is less than 10% of normal controls. However, assay of the ARSA enzyme activity alone is not sufficient for diagnosis; ARSA pseudodeficiency, which is characterized by enzyme activity that is 5~20% of normal controls does not cause MLD. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system. The myelin sheath is a fatty covering that protects nerve fibers. Without it, the nerves in the brain (central nervous system – CNS) and the peripheral nerves (peripheral nervous system – PNS) which control, among other things the muscles related to mobility, cease to function properly.Arylsulfatase A is activated by saposin B (Sap B), a non-enzymatic proteinaceous cofactor.