Table 4 |.
Candidate symptomatic drugs for treatment of SCAs
SCA type | Candidate drug | Scientific premise | Preclinical study | Comments |
---|---|---|---|---|
SCA6 and other SCAs | 4-Aminopyridine | Restoration of pacemaker activities of Purkinje cells by blocking the voltage- dependent family of potassium channels87 | Alleviated motor coordination deficits and restored Purkinje cell firing precision in SCA6 mice homozygous for 84 polyQ repeats87 | Approved by the FDA for symptomatic improvement of walking in multiple sclerosis. A randomized, double- blind, placebo- controlled study showed a decreased number of attacks in patients with episodic ataxia 2 (reF.213). A phase I study214 and a small open- label study215 have been done in patients with SCAs |
SCA2 and other SCAs | Chlorzoxazone | KCNN1 channel activator. Normalization of the Purkinje cell spontaneous firing rate in SCA2 transgenic mice with 58 polyQ repeats100 and in Cacna1a- mutant mice93 | Not yet done | Chlorzoxazone is approved by the FDA and has been used extensively as a muscle relaxant |
SCA44 | Nitazoxanide | Negative allosteric modulator of metabotropic glutamate receptor 1 and 5 with potent inhibition of mutant forms of these receptors in transfected cells214 | Not done in SCA44 models, but similar modulators alleviated ataxia in an SCA1 mouse model216,217 | Nitazoxanide is approved by the FDA and is used for various helminthic, protozoal and viral infections218 |
KCNN1, small-conductance calcium-activated potassium channel protein 1; polyQ, polyglutamine; SCA, spinocerebellar ataxia.