When the arylsulfatase A enzyme level is normal but the sulfatides are still high – meaning that they are not being broken down because the enzyme is not activated – the resulting disease is saposin B deficiency, which presents similar to MLD. Saposin B Deficiency is very rare, much more rare than traditional MLD. The enzyme that is present is not "enabled" to a normal level of efficiency and cant break down the sulfatides which results in all of the same MLD symptoms and progression.A 2011 study contended sulfatide is not completely responsible for MLD because it is nontoxic. It has been suggested lysosulfatide, sulfatide which has had its acyl group removed, plays a role because of its cytotoxic properties in vitro. Genetics
MLD has an autosomal recessive inheritance pattern.
The researchers published 2-year outcomes for the first three patients in July 2013. Results were described as promising. The Phase I/II clinical trial is complete. No additional patients are being recruited while the data is analyzed and work progresses to improve the manufacturability and repeatability of the technology while expansion to other geographies to increase access is being considered. Recruiting was completed for the 20 patient cohort in April 2015, which includes an expansion in December 2014 to add 6 additional patients. Inclusion criteria are pre-symptomatic late infantiles and both pre- and early-symptomatic juveniles. See details on inclusion criteria and the trial protocol here. The trial was at a single center at the San Raffaele Institute in Milan, Italy. All costs were to be paid by the researchers. This was a 3-year study. In March 2013, the last of the 8 primary trial patients started therapy. The trial had several compassionate access patients and ultimately was expanded to 20 patients
In late 2013 GSK exercised its option for the San Rafaelle gene therapy technology and is working with the Milan Investigators to prepare for the next phase of study. Intracerebral Gene therapy – A Phase I/II Clinical Trial started recruiting in Paris in late March, 2013 for an Intracerebral Gene Therapy clinical trial where special "vectors" carrying genetically modified material are directly injected into a dozen sites in the brain. The hope is that the corrected cells and the enzyme they produce will then diffuse into surrounding areas of the brain.