Research Towards Effective Therapies and Clinical Trials
Bone Marrow and Stem Cell Transplant Therapies
- Several trials are underway to continue to improve the effectiveness and reduce the risks of bone marrow and stem cell transplants. Cord blood transplants and reduced preparative routines are being studied.
- Families are cautioned that there are unregulated hucksters usually operating in Central or South America, or China that would be happy to take your money and have you believe stem cell infusions will "cure" MLD. These claims are false.
Gene therapy
- Two different approaches to gene therapy are currently being researched for MLD.
- Italian researchers at the San Raffaele Telethon Institute are testing a novel approach combining gene therapy with a stem cell transplant. Recruiting for the Italian Phase I/II Clinical Trial formally started on March 24, 2010 after approval from the Italian Authorities. The trial is testing the efficacy and safety of an autologous (using the patient's own cells) hematopoietic stem cell transplant (HSCT) after genetic modification to deliver a super-therapeutic (over-expressing) ARSA enzyme to the nervous system by the route of the blood cells. Using the patient's own stem cells with genetic correction should reduce or eliminate the complications of graft vs. host disease and provide a long term solution to proper ARSA expression in MLD patients. Bench and animal tests showed positive results.
- 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 is single center in Milano, Italy. All costs to be paid by the researchers. This is a 3 year study. Five patients have been enrolled, four have completed the transplant, and recruiting is still underway. It is too early to determine efficacy.(Current January 2012)
- A French group is exploring a direct injection into the brain. They anticipate starting clinical trials in 2012 (current as of January 2012)
- Italian researchers at the San Raffaele Telethon Institute are testing a novel approach combining gene therapy with a stem cell transplant. Recruiting for the Italian Phase I/II Clinical Trial formally started on March 24, 2010 after approval from the Italian Authorities. The trial is testing the efficacy and safety of an autologous (using the patient's own cells) hematopoietic stem cell transplant (HSCT) after genetic modification to deliver a super-therapeutic (over-expressing) ARSA enzyme to the nervous system by the route of the blood cells. Using the patient's own stem cells with genetic correction should reduce or eliminate the complications of graft vs. host disease and provide a long term solution to proper ARSA expression in MLD patients. Bench and animal tests showed positive results.
Enzyme replacement therapy (ERT)
- Shire Human Genetic Therapies (Shire HGT), a division of Shire PLC of the UK, is now recruiting for their clinical trial for their intrathecal HGT-1110 product . (current June 2012)
- Additional clinical trial information, including inclusion criteria, can be found on the MLD Foundation website here.
- The clinical trial is a 40 week multi-site European study of 18 children in three different dosing cohorts. The 'no treatment' placebo arm was removed in June 2010
- HGT-1110 has orphan product status in both Europe and the United States.
- History: Shire suspended development of the Metazyme intravenous ERT product in 2010. It was in clinical trial when it was acquired from Zymenex in 2008 (subsequently renamed HGT-1111 by Shire) after it was shown to not have sufficient efficacy by a Phase I/II clinical trial in Europe. The initial study completed September 2008 and the extension study completed October 2010 with the cessation of product supply to trial participants.
Substrate reduction therapy
- Zacharon Pharmaceuticals from San Diego is initiating 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 January 2012)
- 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 January 2011)
Research & Clinical Trial updates provided by the MLD Foundation''
Read more about this topic: Metachromatic Leukodystrophy
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