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Funded Studies

Evaluation of the neuroprotectivity ability of Zymes' water-soluble CoQ10 (WS-CoQ10) in animal models of PD; preclinical validation and dose optimization for clinical study

Objective/Rationale:
Coenzyme Q10 is a lipid soluble naturally occurring compound essential for energy production and defence against oxidative stress.  Recent clinical studies indicate that it may slow the progression of Parkinson’s disease (PD) when used in relatively high doses. Zymes LLC is developing a novel formulation consisting of CoQ10 and vitamin E (WS-CoQ10), licensed from the National Research Council Canada.  This formulation is water-soluble, readily applicable and offers a near-complete protection for dopamine nerve cells in the pre-clinical models of PD as a result of its prophylactic application.   In this project, the effectiveness of WS-CoQ10 in halting the progressive loss of dopamine nerve cells, characteristic of PD, will be tested.

Project Description:
PD is a chronic progressive non-curable neurodegenerative disease in which excessive oxidative stress and energy failure cause the death of brain nerve cells producing dopamine (a chemical that controls movement) leading, initially, to the loss of  movement  coordination.  The loss of dopamine cells in the brain can be re-capitulated in pre-clinical models as a result of systemic injections of certain neurotoxins.  The researchers will inject these neurotoxins into two types of pre-clinical models to initiate the death of dopamine-producing nerve cells and examine the ability of WS-CoQ10 to stop the progression of neurodegeneration.  The models will receive the WS-CoQ10 solution in drinking water (3, 6 and 12 mg/kg/day) starting at different time points after neurotoxin exposure.  The survival of dopamine cells will be examined using various biochemical, histological techniques and behavioural parameters.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Presently, there is no cure and no effective long-term treatments for PD.  The components of the WS-CoQ10 formulation (CoQ10 and Vitamin E) are capable of neutralizing the most important factors ( i.e.,  oxidative stress and energy failure) contributing to the Parkinsonian neurodegeneration. Hence they might be able to slow or stop the progressive loss of dopamine nerve cells, ultimately, leading to better management of PD and better quality of life for PD patients.

Anticipated Outcome:
CoQ10 is poorly absorbed by tissues, especially, by the brain and it is very difficult to deliver therapeutically effective doses.  It is expected that the water-solubility of the composition of WS-CoQ10 (two bioactive components delivered simultaneously) will offset these drawbacks, allowing for greater bioavailability.  Thus, these studies will allow for establishment of an effective dose and the mode of WS-CoQ10 delivery, paving the way for future clinical trials.
 

Final Outcome

Pre-clinical research with the Zymes’ novel water-soluble formulation of CoQ10 along with Vitamin E (Ubisol-QE) in two different pre-clinical models of Parkinson’s disease has yielded interesting and encouraging results. Coq10 is readily absorbed and taken up by brain cells after oral delivery. Post- lesion feeding of this formulation orally at a low amount of 6 mg/kg/day was able to halt the brain cell death and thus progression of neuronal loss in a pre-clinical model. Furthermore, the protective effects of this formulation were demonstrated by improved behavioral motor/balance activity in pre-clinical models. Our research also indicated that it is necessary for Ubisol-QE to be fed continuously to sustain the protection of dopamine neurons.  These results indicate that this formulation could be a potential therapeutic candidate to halt the progression of Parkinson's disease.  

Posters and Presentations

1. Invited presentation at the 8th International Congress of Pharmaceutical Sciences CIFARP 2011 Ribeirao Preto, Brazil, August 21-24, 2011 entitled “Therapeutic opportunities for antioxidants in the management of neurodegeneration: lessons from the application of water-soluble Coenzyme Q10 (WS-CoQ10)” by Jagdeep K. Sandhu and Marianna Sikorska, Neurogenesis and Brain Repair Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada
Jerome Cohen and Siyaram Pandey, Departments of Biochemistry & Psychology University of Windsor, Windsor, Ontario, Canada

2. NHPRS-03-03: Annual Natural Health Products Research Society Conference “Multidisciplinary Approaches to Modern Therapeutics”, Hilton Montreal Bonaventure, Montreal, QC, May 24-27, 2011. Platform presentation


Researchers

  • Shelley B. Weinstock, PhD

    Hasbrouck Heights, NJ United States


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