An open-label pilot study with high-dose thiamine in Parkinson's disease.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically characterized by motor symptoms (bradykinesia, tremor, rigidity, postural instability) and non-motor symptoms (hyposmia, sleep disorders, autonomic and sphincteric dysfunctions, fatigue, pain, depression, and cognitive disorders) (Sprenger and Poewe, 2013). The neuropathological hallmark of PD is the degeneration of the pigmented dopaminergic neurons in the substantia nigra; other nuclei involved in neurodegeneration are locus coeruleus, reticular nuclei of brain stem, dorsal motor nucleus of vagus, basal nucleus of Meynert, amygdala, CA2 area of hippocampus, and frontal cortex. At the onset of parkinsonian symptoms, the neuronal loss is quite 70% in the lateral ventral part and 50% in the caudal part of the substantia nigra (Kordower et al., 2013). For this reason, and for the long time between the cellular onset and the clinical onset of the disease, it is mandatory to develop new therapies with disease-modifying and neuroprotective actions. The gold standard therapy for PD is always levodopa, while other currently validated treatments are dopamine agonists, cathecol-O-methyltransferase inhibitors, monoamine-oxidase-B inhibitors, and amantadine (Poewe et al., 2010; Sprenger and Poewe, 2013).