Exploring Curcumin and Curcumin Derivatives as putative Epigenetic target of Histone Deacetylase (HDAC) inhibition in Parkinson Disease
Therapeutics Development Initiative, 2009
Our project is to explore cutting-edge nano- biotechnology advances in formulating curcumin extracted from Curry as potential drug candidates in treatment of Parkinson disease. Previous studies in neural tissue culture and animal models of PD suggested Curcumin may be a safe neuroprotectant drug targeting gene-environment interaction (“epigenetics”) and prevent or slow progression of PD. By measuring the amount of curcumin transferred from the blood to nerve cells in the brain following intravenous injection, we can determine optimal dosages for each of the three formulations.
Our protocol consists of intravenous administering each of the three Curc formulations in 3 dosages to C57BL6/J mice along with vehicle control. Blood samples are taken at 1 hr, 2 hr and 4 hr after injection for measuring curcumin. Following blood sampling, the mice are sacrificed and brain regions relevant to PD are dissected out for measuring curcumin levels. By pairing blood and brain curcumin levels we will determine the brain uptake and the intravenous dosage required to achieve the brain curcumin level effective against Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Current medications provide relief from symptoms by limiting dopamine breakdown or replacing dopamine, a neurotransmitter produced in specialized nerve cells of the brain. Recently, innovative Industry-Academic partnerships have discovered promising therapeutic targets towards finding a cure for PD. Curcumin is unique in its multiple actions in protecting dopamine neuronal loss through regulating enzymes breaking down dopamine and hitting multiple signals and genes “turned off or off “. Curcumin also reduces inflammation. Curcumin formulations can be the novel frontier in PD therapeutics.
Our project once completed will provide crucial preclinical data on the distribution of the three nano-curcumin formulations administered intravenously throughout the brain in adequate amounts to halt the progressive destruction of nerve cells. We anticipate that nanocurcumin formulations simultaneously preventing worsening of Parkinson symptoms through activating the neural repair pathways to restore the balance between the signature neurotransmitter, dopamine and endogenous neuro-chemicals in the brain. Our translational research strategy will be the first step to catalyse Curcumin formulations from drug targets to potential drug candidates. Data on dosage and administration will set the stage for launching Phase 1/II clinical trial on Curcumin for PD. Our research strategy with Nano-Curc formulations is both biotechnology-driven and evidence-based and drives home the role of dietary factors in prevention and treatment of PD.
INTERIM PROGRESS REPORT
The data presented indicate that curcumin formulations composed with liposomes, acrylic polymers, and PLGA injected intravenously cross the blood brain barrier. The first two formulations localize in the hippocampus, striata, and brain stem. The novel observations of curcumin localization in specific brain sites at concentrations known to induce neurogenesis and neuroplasticity support clinical applications of prevention, therapy, and remediation of these associated, site-specific diseases. The concentrations achieved in these sites are within levels affording neuroprotection and application to Parkinson's disease and other neuropathic disorders. Since the dosage-related accumulation rates and reside times of the formulations in these specific sites may impact their clinical efficacy, these observations suggest a need for additional experimental studies in pre-clinical models and patients with hippocampus, striatum, brainstem and cortical associated neurodegenerative disorders.
President and CEO at Sign Path Pharma
Location: Quakertown, Pennsylvania