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Minocycline Clinical
Trial in ALS
In this trial, high doses of minocycline will be administered to study participants in hopes of obtaining the greatest potential of neuroprotective benefit. ALS is a progressive neurodegenerative disorder without any cure or known treatment that significantly improves function. Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Minocycline, currently approved by the U.S. Food and Drug Administration for treatment of bacterial infections, is an antibiotic in the tetracycline group that penetrates the brain and spinal cord when taken orally. Minocycline was selected for study because its effects may inhibit motor nerve degeneration at several points. It likely inhibits cell death pathways by preventing both pro-apoptotic (apoptosis is a process which may lead to cell demise in neurodegenerative disorders) and pro-inflammatory enzyme activation. Laboratory studies have linked inducible nitric oxide synthase (iNOS) and caspase enzyme activation to motor nerve cell death in ALS. The drug inhibits iNOS, caspases and other enzymes, which are involved in cell death pathways such as apoptosis. Minocycline slows deterioration in laboratory models of neurodegeneration including Parkinson disease and Huntington disease, which have modes of cell death similar to ALS. It also has neuroprotective benefit in experimental stroke and trauma, and it has proven efficacy in human inflammatory arthritis, separate from its antibiotic properties. Several laboratories have now shown that minocycline also delays disease progression in the ALS SOD1 mouse model. Intraperitoneal injections of minocycline have provided an increase in lifespan of 11-16% compared to placebo-treated mice. Two preliminary human trials were conducted to test the initial safety and tolerability of high doses of minocycline prior to embarking on the definitive phase III trial. In those studies minocycline was reasonably well tolerated, but gastrointestinal side effects and abnormalities of liver and kidney function became more prominent at the higher doses, necessitating close monitoring while taking the drug. The objective of this phase III clinical trial is to determine whether minocycline slows disease progression and helps maintain function in patients with ALS. In this multicenter trial, participants will be randomly assigned to treatment with the study drug or a placebo. The trial investigators will measure changes in function, using the ALS Functional Rating Scale, and measures of strength, pulmonary function, survival and quality of life. Each participant will undergo monthly outpatient evaluations and analysis of laboratory and adverse events for 13 months. Subjects will be allowed to take riluzole, but not other investigational agents such as creatine or Celebrex during the trial. Subjects with kidney disease, liver disease, or lupus will be excluded. Because minocycline may cause harm to the unborn child, women of childbearing age cannot be pregnant and must practice adequate birth control. This is the first phase III trial in human ALS of a medication that acts as both an anti-apoptotic and anti-inflammatory agent. Participation in the trial will allow patients with ALS to contribute to the scientific understanding of the disorder and to the discovery of treatments that impact its course. Any compound proven in a controlled study to slow the course of human ALS will be of immediate importance. If you live in the tri-state area and are interested in the Minocycline Trial contact: Jackie Montes, PT If you live outside the tri-state area and are interested in the Minocycline Trial contact: Nayra Gad, MA
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The
multi-center clinical trial of Minocycline is anticipated to begin enrollment
throughout the United States by the end of July. In preparation for this
we asked our Associate Medical Director, Dr. Paul Gordon to provide an
overview of the rationale for testing Minocycline in ALS and the project
goals. 
