Metachromatic leukodystrophy (MLD) is an inherited condition characterized by the accumulation of fats called sulfatides in cells, especially cells of the nervous system. Affected individuals experience progressive deterioration of intellectual functions and motor skills, such as the ability to walk. This condition is inherited in an autosomal recessive pattern and is caused by genetic changes in the arylsulfatase A (ARSA) gene. MLD is characterized by three clinical subtypes: late-infantile MLD, juvenile MLD, and adult MLD.
Existing studies have shown that the age of onset for MLD patients is related to the enzyme activity of ARSA. The higher the enzyme activity, the later the onset. Rapid disease progression upon onset can be observed for the late-infantile and juvenile-onset patients, which would quickly lead to death within a few years if no treatment were applied. Currently, there is no curative treatment option for MLD patients, so the focus is on improving quality of life by symptom management.
Combining gene therapy and hematopoietic stem cell transplantation is the most promising treatment as of now. Asymptomatic or early symptomatic juvenile-onset patients may benefit more from this treatment. Bone marrow transplantation stabilizes neurocognitive function. However, there is still a gradual loss of motor skills. In late teenage and adult-onset patients, bone marrow transplantation may slow down disease progression.
Encouraging results have been achieved using gene therapy to deliver the wild-type ARSA gene, as well as using combined gene-cell therapy with mesenchymal stem cells.
