These cells are transduced ex vivo using a lentiviral vector encoding the human arylsulfatase A gene to insert a functional gene to produce the ARSA enzyme. When the modified cells are transplanted back into the patient as a one-time infusion, the cells have been shown to produce the missing ARSA enzyme. The children by the age of five were all in good condition and going to kindergarten when normally by this age, children with the disease can not even speak. Additional information can be found on the MLD Foundations Gene Therapy page and at the Clinical Trials.gov site. In November, 2020, Orchard Therapeutics acknowledged IND discussions with the FDA as the part of their effort to seek FDA approval in the USA. A trial for late juveniles was launched in February 2020. Orchard Therapeutics acquired the gene therapy IP from GSK in April 2018. Recruiting for the Phase I/II Clinical Trial formally started on March 24, 2010, after approval from the Italian Authorities. Recruiting the initial cohort of 8 patients was completed in mid-March 2013. The trial was to test the efficacy and safety of autologous (using the patients own cells) hematopoietic stem cell transplantation (HSCT) after genetic modification to deliver a super-therapeutic (over-expressing) ARSA enzyme to the nervous system by the route of the blood cells. Using the patients own stem cells with genetic correction should reduce or eliminate the complications of graft vs. host disease and provide a long-term solution to proper ARSA expression in MLD patients. Bench and animal tests showed positive results.
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.