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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Aminopyridines and Acetyl-DL-leucine: New Therapies in Cerebellar Disorders

Author(s): Roger Kalla and Michael Strupp*

Volume 17, Issue 1, 2019

Page: [7 - 13] Pages: 7

DOI: 10.2174/1570159X16666180905093535

Price: $65

Abstract

Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain forms of cerebellar ataxia. This article will give an outline of the present pharmacotherapy of different cerebellar disorders. As a current key-therapy for the treatment of downbeat nystagmus 4-aminopyridine (4-AP) is suggested for the treatment of downbeat nystagmus (5–10 mg Twice a day [TID]), a frequent type of persisting nystagmus, due to a compromise of the vestibulo-cerebellum. Studies with animals have demonstrated, that a nonselective blockage of voltage-gated potassium channels (mainly Kv1.5) increases Purkinje- cell (PC) excitability. In episodic ataxia type 2 (EA2), which is frequently caused by mutations of the PQ-calcium channel, the efficacy of 4-AP (5–10 mg TID) has been shown in a randomized controlled trial (RCT). 4-AP was well tolerated in the recommended dosages. 4-AP was also effective in elevating symptoms in cerebellar gait ataxia of different etiologies (2 case series).

A new treatment option for cerebellar disease is the amino-acid acetyl-DL-leucine, which has significantly improved cerebellar symptoms in three case series. There are on-going randomized controlled trials for cerebellar ataxia (acetyl-DL-leucine vs placebo; ALCAT), cerebellar gait disorders (SR-form of 4-AP vs placebo; FACEG) and EA2 (sustained-release/SR-form of 4-AP vs acetazolamide vs placebo; EAT2TREAT), which will provide new insights into the pharmacological treatment of cerebellar disorders.

Keywords: Cerebellar ataxia, central vestibular disorders, aminopyridines, 4-aminopyridine, episodic ataxia type 2, downbeat nystagmus, acetyl-DL-leucine.

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