The advent of effective enzyme therapies for the visceral manifestations of Gaucher disease has stimulated renewed interest in both the basic science and therapeutics for the neuronopathic Gaucher disease variants, types 2 and 3.  In numerous Scientific  workshops, led by Dr. Tony Futerman and hosted by the PBRF, basic scientists discussed the mechanisms causing the brain disease in Gaucher disease.  The discussion was vigorous and will lead to many interesting and important discoveries related to the neurologic involvement in Gaucher disease.

A major recommendation coming from that workshop was to begin the development of a clinical trial protocol for a remaining major unmet medical need in Gaucher disease – treatment of the central nervous system involvement (the brain) in Gaucher disease type 3. The development of clinical trial protocols or assessment tools, that are not specific to the mode of therapy, are critically needed to assess potential therapeutic benefit for Gaucher disease type 3. Because of this general need, the group recommended a new workshop to address the global scope of a treatment protocol or clinical trial design that could determine effectiveness in treating Gaucher disease Type 3 brain involvement.

The workshop members recommended that a small group convene within the coming months to initiate discussions about trial design and to have experts provide measurable outcomes for assessments of new therapies. This would be sponsored by, but completely independent of, at least 4 major companies involved in the treatment of Gaucher disease, including Genzyme/Sanofi, Pfizer/Protalix, Shire/HGT, and Amicus Therapeutics. The workshop would be sponsored and organized by the Children’s Gaucher Research Fund (CGRF) and be conducted by independent experts from the United States and Europe. Drs. Gregory Grabowski, from the US, and Ashok Vellodi, from the UK, agreed to spearhead this effort. The workshop will consist of 6 Gaucher experts, 3 from the US and 3 from Europe, with expertise in the neuropathic manifestation of Gaucher disease.  In addition, 1 or 2 additional experts will be involved for specific aspects of neurologic assessments, for example, brain imaging and/or biomarkers of brain involvement. Each of the companies mentioned above may have one representative at the meeting.

The overall goal of this initial meeting is to develop a common vocabulary and assessments for the neuropathic involvement by Gaucher disease that will lead to measurable endpoints of clinical relevance to assess therapeutic benefit. These metrics may include overall assessments of cognitive and/or neurologic involvement. The group will also address the issue of reversibility of the brain manifestations. The discussions will be facilitated by a highly experienced physician with extensive previous work with the FDA (Food and Drug Administration – USA) and the EMA (European Medicines Agency) so that a document can be tailored for input from the EMA and FDA. After this initial workshop, a second workshop is anticipated. This second workshop that will include the same group of neurologist, plus representatives of the EMA and FDA, patient groups interested in neuropathic Gaucher disease, and additional neurologists. Such additional input will be essential. The goal is to produce a document for the overall assessment of therapeutic outcomes of the neurologic involvement in Gaucher disease type 3.

Fortunately, a number of physicians and staff at the EMA and FDA have previous experience in this area and will be able to provide valuable insights and guidance for the final development of a clinical trials protocol. The final product will be a protocol for discussions with the EMA and the FDA in their deliberations of any type of therapy for the neuropathic manifestations of Gaucher disease. This document will be available in the public domain either as a publication or from the CGRF to investigators and/or companies with a significant interest in developing treatments for the neuronopathic variants of Gaucher disease.

Gregory A. Grabowski M.D.
Professor and Director
Division of Human Genetics
Cincinnati Children’s Hospital Medical Center