Metachromatic leukodystrophy is a neurological disease of the lysosomal deposit that has a significant impact given the implications for the neurodegenerative deterioration of the patient. Currently, there is no treatment available that reverses the development of characteristic neurological and systemic symptoms. Objective. Carry out an updated bibliographic search on the most critical advances in the treatment and diagnosis for LDM. A retrospective topic review published in English and Spanish in the Orphanet and Pubmed databases. Current treatment options, such as enzyme replacement therapy and hematopoietic stem cell transplantation aimed at decreasing the rapid progression of the disease, improving patient survival; however, these are costly. The pathophysiological events of intracellular signaling related to the deficiency of the enzyme Arylsulfatase A and subsequent accumulation of sulphatides and glycosylated ceramides have not yet been established. Recently, the accumulation of C16 sulphatides has been shown to inhibit glycolysis and insulin secretion in pancreatic cells. The significant advance in technology has allowed timely diagnosis in patients suffering from LDM; however, they still do not have an effective treatment.

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Metachromatic leukodystrophy is a neurological lysosomal deposit disease that affects public health despite its low incidence in the population. Currently, few reports are available on pathophysiological events related to enzyme deficiencies and subsequent sulfatide accumulation. This research aims to examine the use of metformin as an alternative treatment to counteract these effects. This was evaluated in human Schwann cells (HSCs) transfected or non-transfected with CRISPR-Cas9, and later treated with sulfatides and metformin. This resulted in transfected HSCs showing a significant increase in cell reactive oxygen species (ROS) production when exposed to 100 µM sulfatides ( p = 0.0007), compared to non-transfected HSCs. Sulfatides at concentrations of 10 to 100 µM affected mitochondrial bioenergetics in transfected HSCs. Moreover, these analyses showed that transfected cells showed a decrease in basal and maximal respiration rates after exposure to 100 µM sulfatide. However, maximal and normal mitochondrial respiratory capacity decreased in cells treated with both sulfatide and metformin. This study has provided valuable insights into bioenergetic and mitochondrial effects of sulfatides in HSCs for the first time. Treatment with metformin (500 µM) restored the metabolic activity of these cells and decreased ROS production.