Botez M I, Botez-Marquard T, Mayer P, Marchand L, Lalonde R, Reader T A
Hôtel-Dieu Hospital, Neuroscience Research Centre, Department of Physiology, University of Montréal, Québec, Canada.
Med Hypotheses. 1998 Nov;51(5):381-4. doi: 10.1016/s0306-9877(98)90032-9.
Actual therapeutic assays in spinocerebellar ataxias, i.e. in Friedreich's ataxia (FA) and olivopontocerebellar atrophy (OPCA) are discussed in relation to (i) the serotoninergic theory; (ii) the excitotoxic action of glutamate; and (iii) cerebrospinal fluid thiamine deficiency in ataxic patients. Data from the literature show that neurochemical deficiencies arising from cerebellar damage in both FA and OPCA patients are multiple. Assays of replacement and neuroprotective therapeutics with a single drug have produced controversial data or mildly effective results. Consequently, it is hypothesized that a drug cocktail, i.e. L-5-hydroxytryptophan, thiamine and amantadine hydrochloride, would be more beneficial. This cocktail proved to be useful in open studies, improving respiratory disorders in FA patients. More powerful inhibitors of N-methyl-D aspartate receptor channels should be tried initially in animal experiments.
本文结合以下三方面讨论了脊髓小脑共济失调(即弗里德赖希共济失调(FA)和橄榄脑桥小脑萎缩(OPCA))的实际治疗试验:(i)血清素能理论;(ii)谷氨酸的兴奋性毒性作用;(iii)共济失调患者脑脊液中硫胺素缺乏。文献数据表明,FA和OPCA患者小脑损伤引起的神经化学缺陷是多方面的。用单一药物进行替代和神经保护治疗的试验产生了有争议的数据或效果一般的结果。因此,有人推测药物组合,即L-5-羟色氨酸、硫胺素和盐酸金刚烷胺,可能更有益。这种药物组合在开放性研究中被证明是有用的,可改善FA患者的呼吸障碍。应首先在动物实验中尝试更有效的N-甲基-D-天冬氨酸受体通道抑制剂。