NEW YORK – The loss of dopaminergic neurons is known to be a pivotal mechanism in Parkinson’s disease (PD), but early research into the anticonvulsant drug valproic acid has found it may produce antioxidant and neuroprotective actions that enhance the effects of levodopa, as reported at the International Conference on Parkinson’s Disease and Movement Disorders.
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Dr. Ece Genc
“Levodopa had better activity than valproic aside, but when they are used together, they have really very effective results,” said Ece Genç, PhD, of Yeditepe University in Istanbul, who reported on the research conducted in her laboratory.
Dr. Genç noted her research in rats has focused on the possible mechanisms of neurodegeneration in Parkinson’s disease: mitochondrial dysfunction, oxidative stress and tissue damage, disruption in protein organization, and cell death caused by inflammatory changes. “Dopamine metabolism can itself be a toxic compound for the neurons,” she said, explaining that dopamine is critical for stabilizing nerve synapses, but its dysregulation can cause oxidative stress of the neurons, leading to cell death.
A key mechanism in the tremors PD patients experience is histone deacetylase, Dr. Genç said. “Histone acetylation and deacetylation are extremely important in these processes,” she said (Neurosci Lett. 2018 Feb 14;666:48-57). “Valproic acid is an antiepileptic drug; it is used in bipolar disorder and migraine complexes, but one of the major actions of valproic acid is that it caused histone deacetylase in the patients.”
Previous research that has shown the rotenone model of valproic acid provided neuroprotection helped drive her research, she said (Neurotox Res. 2010;17:130-41).
Future directions in her research would aim to synchronize cell cultures and in-vivo studies, and try to develop a method to measure alpha-synucleinopathy – abnormal levels of alpha-synuclein protein in the nerves of people with neurodegenerative diseases. “I think that alpha-synucleinopathy is the key word here,” Dr. Genç said. “We have to be very careful with alpha-synuclein proteins and their presence in individuals and, of course, with the successful use of valproic acid and histone deacetylase in patients, we can look for new drugs with less adverse effects.”
One of the drawbacks of valproic acid is that it affects so many different channels in the body. “We have to find some drugs with more targeted action.” Dr. Genç said.
Dr. Genç did not report any relevant disclosures.