Genomic sequencing may also confirm MLD, however, there are likely more mutations than the over 200 already known to cause MLD that are not yet ascribed to MLD that cause MLD so in those cases a biochemical test is still warranted. Newborn screening
MLD Foundation formally launched a newborn screening initiative in late 2017. The screen development started in the early 2010s at the University of Washington Gelb Biochemistry lab. A deidentified pilot study launched in April 2016 in Washington state. Positive results led to MLD being included in the ScreenPlus identified baby research project in New York state, which is currently scheduled to launch in Q12021. Treatment
There is currently no approved treatment for MLD in symptomatic late infantile patients or for juvenile and adult-onset with advanced symptoms. These patients typically receive clinical treatment focused on pain and symptom management.Pre-symptomatic late infantile MLD patients, as well as those with juvenile or adult MLD that are either presymptomatic or displaying mild symptoms, can consider bone marrow transplantation (including stem cell transplantation), which may slow down the progression of the disease in the central nervous system. However, results in the peripheral nervous system have been less dramatic, and the long-term results of these therapies have been mixed.In 2020 the European Medical Agency, approved the Cell Therapy Drug Libmeldy for treatment of infantile and juvenile forms of metachromatic leukodystrophy in Europe. Libmeldy is a type of advanced therapy medicine called a ‘gene therapy’. This type of medicine works by delivering genes into the body.
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.