Treatment options in Huntington's disease

Besides monogenetic inheritance, neuroacanthocytosis syndromes like McLeod- and Levine-Critchley syndrome share aspects of motor and mental symptomatology with Huntington’s disease (HD). Since an expansion of a trinucleotide repeat on chromosome 4p16.3 had been identified as the mutation causing HD in 1993, much hope has been raised that it would take only a short time span to decode the molecular pathway “from gene to symptoms” and subsequently develop causal therapeutic strategies for this devastating progressive disease. However, though many fragments of the molecular “puzzle” of HD pathology have been revealed nearly ten years after the discovery of the HD gene, causal targeting of its molecular pathology is still missing. Besides conventional symptomatic treatment of psychiatric and neurologic symptoms of HD with antihyperkinetic (e.g. dopamine-antagonists, tetrabenazine) and psychotropic (e.g. antipsychotics, antidepressants) drugs, substances which are supposed to exert “neuroprotective” effects (e.g. remacemide, coenzyme Q10, riluzole, creatine, memantine) have been or are being examined in controlled clinical studies in the US and Europe. Up to now, none of these substances has been found to exert statistically significant effects on slowing down the progression of HD symptomatology, but some of the studies are still under way. Data from in vitro experiments and HD mutant animal models suggest strategies to either prevent aggregation of expanded polyglutamines, activation of microglia, or inhibition of caspase cleavage. Spectacular results have been published one year after transplantation of fetal basal ganglia tissue in single HD cases. However, long-term observations are missing and from a methodological point it is quite questionable, whether local transplants into HD brains affected by systematic neurodegeneration which is not confined to the basal ganglia will be able to exert enduring positive effects. Overall, after nearly ten years of research in therapeutic options since the discovery of the HD gene we are still far from real therapeutic breakthroughs. With respect to HD sufferers and their families, scientists in the field should be reluctant to awaken illusionary hopes and expectations by publishing or interpreting preliminary results which are far from being able to be realized as promising therapeutic options.