Abstract:

Parkinson 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). At the onset of parkinsonian symptoms, the neuron loss is quite 70% in the lateral ventral part and 50% in the caudal part of substantia nigra. 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. Recent data showed that in some inherited and degenerative diseases of the nervous system the pathogenesis of the symptoms could be linked to a focal deficiency of thiamine (vitamin B1) due either to dysfunction of intracellular thiamine transport or to structural enzymatic abnormalities. Thiamine is a cofactor of enzymes involved in fundamental pathways of energetic cell metabolism, particularly critical in glucose metabolism. Recent clinical studies showed a considerable and stable improvement of motor and non-motor symptoms in patients affected by PD with intramuscular high-dose thiamine (100 mg) administered twice a week. Therefore, we decided to extend the treatment with high doses of thiamine to a series of PD patients in order to clarify the potential effect of thiamine in this disease. We found that long-term treatment with intramuscular administration of thiamine has led to significant improvement of motor and non-motor symptoms of patients with PD; this improvement was stable during time and without side effects. Our report represents an important contribution to PD therapy, although further experience is necessary to exclude placebo effect and to confirm the present observation, with clinical, cellular, and molecular data. The aim of future studies will be to investigate the clinical, restorative, and neuroprotective effects of long-term treatment with thiamine in PD.