https://www.ncbi.nlm.nih.gov/pubmed/24775711

April 2nd, 2014

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease.

Abstract
Although the support for the use of antioxidants, such as coenzyme Q10 (CoQ10), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ10 (Ubisol-Q10) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q10 was delivered in drinking water. Prophylactic application of Ubisol-Q10, started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q10 group by day 28). Therapeutic application of Ubisol-Q10, given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ10/kg body weight/day, showing clearly that high doses of CoQ10 were not required to deliver these effects. Furthermore, the Ubisol-Q10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q10 was capable of halting the neurodegeneration already in progress; however, to maintain it a continuous supplementation of Ubisol-Q10 was required. The pathologic processes initiated by MPTP resumed if supplementation was withdrawn. We suggest that in addition to brain delivery of powerful antioxidants, Ubisol-Q10 might have also supported subcellular oxidoreductase systems allowing them to maintain a favorable cellular redox status, especially in astroglia, facilitating their role in neuroprotection. Based on this data further clinical testing of this formulation in PD patients might be justifiable.