Natural History and ERT
Dr. Maria Escolar at Children’s Hospital of Pittsburgh of UPMC is conducting a natural history study of late infantile MLD. The purpose of the study is to understand what happens to the neurodevelopment of children with MLD. The information obtained from the study will help physicians understand if treatments like enzyme replacement infusions or cord blood transplantation are effective in improving or stabilizing the disease progression. To see the invitation to participate in the study, please click here. Click here to read the study details and criteria. To learn more about Dr. Escolar and the Program for the Study of Neurodevelopment in Rare Disorders (NDRD) at Children’s Hospital of Pittsburgh of UPMC, click here.
MLD Enzyme replacement therapy (ERT)
In 2008, Shire HGT purchased the rights to Metazym, an enzyme replacement therapy (ERT) that was initially developed by Zymenex. In February 2009, Shire announced the results of its one-year Metazym trial with 13 late infantile MLD children and noted that no motor or cognitive function effects were observed. Shire had planned to initiate a Phase 2/3 study with intravenous (IV) enzyme replacement therapy but later canceled this after concluding that the IV route of administration was not succeeding. As a result, Shire decided to suspend further development of an IV formulation of arylsulfatase A (ASA) derived from CHO cells, also known as HGT-1111.
Going forward Shire believes that direct delivery to the central nervous system (CNS) offers the best chance for development of a successful treatment for MLD. Shire plans to develop HGT-1110, a formulation of ASA derived from human cells and compatible with direct CNS delivery for MLD patients. This human cell line has been used successfully by Shire for the development of other ERTs for Hunter syndrome, Fabry disease, and type 1 Gaucher disease. Development of the HGT-1110 formulation suitable for direct delivery to the CNS is ongoing, and according to Shire’s website, it is expected to be launched in in the 2013-2016 timeframe.
Volkmar Gieselmann discusses the genetics and new forms of treatment (gene therapy and enzyme replacement therapy) being studied for metachromatic leukodystrophy in the 2008 issue of Aecta Paediatrica. Click here to read the article. Gieselmann is not an advocate of transplant for the late-infantile form of MLD based on a paper published in Bone Marrow Transplant in 2007. This paper describes a case study with only one child who was pre-symptomatic yet MLD degradation continued despite transplant. While The Evanosky Foundation disagrees with this position based on personal experience, the discussion of other treatment studies is interesting. Please note that Dr. Gieselmann was a stockholder of Zymenex, which produced ASA (the enzyme required by MLD patients) for clinical application. In 2008, Zymenex’s ASA technology was purchased by Shire, LLC.