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. 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) main article: enzyme replacement therapy (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 . 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 foundation's 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. no results are known to have been published. (current march 2013) natural history studies main article: natural history study a natural history study (nhs) launched in washington, dc in january 2014 to study 30 patients with additional study centers opened in the us, europe, south america, southeast asia, and south america. due to challenges in recruiting this study has been cancelled. a natural history study has been underway in pittsburgh, pa since november 2012.