Phase 2 Study of 4-Aminopyridine for the Treatment of Episodic Ataxia Type 2

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DESCRIPTION (provided by applicant): Familial episodic ataxia (EA) syndromes are rare and heterogeneous monogenic disorders characterized by dramatic episodes of imbalance and uncoordination. Episodic ataxia type 2 (EA2) is the most common and the best characterized of all the EA syndromes. EA2 caused by mutations in CACNA1A (a neuronal calcium channel gene) typically presents with early onset debilitating ataxia episodes variably associated with nystagmus, headaches, and fluctuating weakness. Since the discovery of dramatic response of EA2 to acetazolamide, acetazolamide has been the first-line treatment for EA2. Yet, some patients are not responsive to acetazolamide, cannot tolerate the side effects, or are allergic to acetazolamide. For these patients (roughly a third of individuals who are currently participating in an ongoing UCLA Episodic Ataxia study as well a collaborative study with the University of Rochester), there are no alternative treatments. 4-Aminopyridine (4AP) was found in Europe to be effective in a few patients with EA2, and an extended release formulation of 4AP by Acorda Therapeutics has just been approved by the FDA in January 2010 for use in patients with multiple sclerosis. With assurance from Acorda to supply 4AP and placebo, a randomized trial is proposed to test the efficacy of 4AP in reducing ataxia episode frequency and secondarily to evaluate its tolerability and its impact on treatment satisfaction and health-related quality of life in patients with EA2. Recruitment of 20 subjects for this 3-year, double-blind, two-crossover, randomized trial of 4AP is proposed.