Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia

Overview

Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches. Purkinje cells are the sole output of the cerebellar cortex: they project inhibitory signals to the deep cerebellar nuclei (DCN), which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement. Recent evidences support the notion that an increase in DCN excitability may be an important step in the development of cerebellar ataxia and point to the underlying molecular mechanisms: the inhibition of small-conductance calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in DCN, correlates with cerebellar ataxia. The rationale of the present project is that SK channel openers, such as riluzole, may have a beneficial effect on cerebellar ataxia. The researchers propose to perform a pilot study investigating safety and efficacy of riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach in patients with chronic cerebellar ataxia.

Forty patients with chronic cerebellar ataxia will be enrolled in a double-bind, randomized, placebo-controlled trial. By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 8 weeks. Electrocardiogram routine laboratory tests and pregnancy tests will be performed before drug administration, after 4 weeks of treatment and at the end of the study (after 8 weeks of treatment). At the same time points the International Cooperative Ataxia Rating Scale (ICARS) for pharmacological assessment of the cerebellar syndrome will be administered to the two groups (riluzole and placebo) of patients. To guarantee the evaluation of the results in blind conditions, the neurologists who will evaluate the ICARS scores will be different from those who will deal with randomisation and follow-up of patients.