Gaucher disease is an inherited functional deficiency of glucocerebrosidase. This enzyme breaks down a fatty substance (lipid) called glucocerebroside, which is present in all cells of the body. When cells renew themselves, the lipids must be broken down and discarded. Because the enzyme does not function well, the lipid builds up in certain tissues, such as the liver and spleen. The nervous system is involved as well; memory is impaired and it is difficult to move the eyes from side to side. It has been shown that repeated infusions of glucocerebrosidase help break down the stored lipid. However, this treatment does not improve any neurological symptoms.

A medicine called OGT 918 has been shown to slow the production of the lipid that builds up in Gaucher disease. It also has been shown to enter the brain. It is hoped that taking OGT 918 will reduce the storage of glycolipids in cells and improve the neurological symptoms of the disease. This clinical trial seeks to evaluate OGT 918 as a treatment for neuronopathic Gaucher disease by assessing changes in eye movement velocity. A secondary goal is to assess the clinical safety and tolerability of OGT 918 therapy.

Up to 30 patients from the National Institutes of Health and the Institute of Child Health (London) will be randomly assigned to OGT 918 or no treatment for 12 months. Study participants must be clinically diagnosed with neuronopathic Gaucher disease, 12 years of age or older, and able to swallow capsules. They must have been stable on ERT for at least 6 months before the study.

Patients receiving OGT 918 will receive a dose of 200 mg OGT 918 three times daily. Data analysis will be done after 12 months. The study will be extended up to 12 months to collect safety and efficacy data. All patients who complete the main study and enter the extension study will receive OGT 918.

During a 4-week screening period, eye movement velocity will be measured. These assessments will be repeated at months 12 and 24. Also at screening and months 12 and 24, the following tests will be done: MRI/CT, to measure spleen and liver volume; pulmonary imaging (by X-ray) and function tests; nerve conduction velocity studies and neuropsychological assessments; evoked response studies (to measure how the brain conducts electrical messages); and tremor measurements. Additional assessments for tremor will be conducted at months 6 and 18.

Plasma samples will be obtained every 3 months to measure disease markers and safety profiles. Proteasome samples will be taken at screening and month 6 to identify proteins that may be associated with Gaucher disease. Blood will be obtained at month 1 from the first 6 consenting patients who have been randomly assigned to take OGT 918. These patients will also have a cerebrospinal fluid sample taken by lumbar puncture at month 1. These samples will be measured for how much OGT 918 is present.

All patients receiving OGT 918 will have an initial assessment 1 week after beginning treatment to evaluate tolerance of the therapy. Clinic visits will be every 3 months. All patients will be asked to keep a simple diary of adverse events and dietary information. Dose levels may be reduced if a patient experiences severe gastrointestinal problems.