Gazulla J, Tintoré M
Department of Neurology, Miguel Servet University Hospital, Zaragoza, Spain.
Acta Neurol Scand. 2007 May;115(5):356-63. doi: 10.1111/j.1600-0404.2006.00752.x.
Voltage-dependent calcium channels (VDCCs) are heteromultimeric complexes that mediate calcium influx into cells; the alpha 1A subunit is the pore-forming subunit specific to the neuronal P/Q-type VDCCs. Spinocerebellar ataxia type 6 (SCA 6) is caused by an abnormal expansion of a CAG repeat in CACNA1A, which encodes the alpha 1A subunit. Heterologous expression of mutated alpha 1A subunits resulted in increased channel inactivation in electrophysiological tests. Gabapentin and pregabalin interact with the alpha 2 delta subunit of the VDCCs and improved ataxia in cases of cortical cerebellar atrophy (CCA) and ataxia-telangiectasia.
A bibliographical review was performed in order to find out if gabapentin and pregabalin could prove useful in the treatment of SCA 6.
Gabapentin and pregabalin slowed the rate of inactivation in recombinant P/Q-type VDCCs. SCA 6 shares neuropathological findings with CCA.
On the basis of the neuropathological identity of SCA 6 with CCA, and of the effect of gabapentin and pregabalin on recombinant VDCCs the authors put forward the hypothesis that these drugs might prove beneficial in SCA 6, as the ataxia would be expected to improve. The authors hope that researchers working with this illness will be encouraged to undertake the appropriate clinical and experimental work.
电压依赖性钙通道（VDCCs）是介导钙离子流入细胞的异源多聚体复合物；α1A亚基是神经元P/Q型VDCCs特有的孔形成亚基。6型脊髓小脑性共济失调（SCA 6）由编码α1A亚基的CACNA1A基因中CAG重复序列异常扩增所致。在电生理测试中，突变α1A亚基的异源表达导致通道失活增加。加巴喷丁和普瑞巴林与VDCCs的α2δ亚基相互作用，并改善了皮质小脑萎缩（CCA）和共济失调毛细血管扩张症患者的共济失调症状。
进行文献综述，以确定加巴喷丁和普瑞巴林是否对SCA 6的治疗有用。
加巴喷丁和普瑞巴林减缓了重组P/Q型VDCCs的失活速率。SCA 6与CCA有共同的神经病理学表现。
基于SCA 6与CCA的神经病理学一致性，以及加巴喷丁和普瑞巴林对重组VDCCs的作用，作者提出假说，认为这些药物可能对SCA 6有益，因为预期共济失调症状会得到改善。作者希望研究这种疾病的人员受到鼓舞，开展适当的临床和实验工作。
