There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population.There are an estimated 3,600 MLD births per year, with 1,900 alive in the US, 3,100 in Europe, and 49,000 alive worldwide with MLD.MLD is considered a rare disease in the US and other countries. Research
Bone marrow and stem cell transplant therapies
Several trials are underway to continue to improve the effectiveness and reduce the risks of bone marrow and stem cell transplants. Gene therapy
(current as of April 2021)
Two different approaches to gene therapy are currently being researched for MLD. Gene therapy with an autologous stem cell transplant – Italian researchers at the San Raffaele Telethon Institute tested a novel approach combining gene therapy with an autologous stem cell transplant.Gene therapy for late infantile and early juvenile patients was approved by the European Commission in December 2020 after receiving a favorable European Medicines Agency CHMP review in October 2020. The product is being marketed in the EU as Libmeldy. Libmeldy is a gene therapy medicinal product, for which CD34+ haematopoietic stem and progenitor cells are collected either from the patients own bone marrow or mobilised peripheral blood.
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.