Ubisol-Q10, a Nanomicellar and Water-Dispersible Formulation of Coenzyme-Q10 as a Potential Treatment for Alzheimer’s and Parkinson’s Disease

Abstract

The world continues a desperate search for therapies that could bring hope and relief to millions suffering from progressive neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD). With oxidative stress thought to be a core stressor, interests have long been focused on applying redox therapies including coenzyme-Q10. Therapeutic use has failed to show efficacy in human clinical trials due to poor bioavailability of this lipophilic compound. A nanomicellar, water-dispersible formulation of coenzyme-Q10, Ubisol-Q10, has been developed by combining coenzyme-Q10 with an amphiphilic, self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (derivatized vitamin E). This discovery made possible, for the first time, a proper assessment of the true therapeutic value of coenzyme-Q10. Micromolar concentrations of Ubisol-Q10 show unprecedented neuroprotection against neurotoxin exposure in in vitro and in vivo models of neurodegeneration and was extremely effective when delivered either prior to, at the time of, and most significantly, post-neurotoxin exposure. These findings indicate a possible way forward for clinical development due to effective doses well within Federal Drug Administration guidelines. Ubisol-Q10 is a potent mobilizer of astroglia, antioxidant, senescence preventer, autophagy activator, anti-inflammatory, and mitochondrial stabilizer. Here we summarize the work with oil-soluble coenzyme-Q10, its limitations, and focus mainly on efficacy of water-soluble coenzyme-Q10 in neurodegeneration.

Bioavailability enhancement of coenzyme Q10: An update of novel approaches

“…[ 68 ] In addition, the nanomicellar formulation of CoQ 10 —Ubisol‐Q 10 has been extensively studied in neurodegenerative disorders such as Alzheimer's and Parkinson's disease as a component of advanced redox therapy against oxidative stress. [ 71,83 ] Remarkable results of intravenous injections of CoQ 10 /caspofungin nanomicelles in increasing CoQ 10 tissue uptake and plasma levels were reported by Wang and Hekimi. [ 76 ] Intravenous injection presented a significant advantage compared to the administration of the liquid form of solubilized CoQ 10 .…”

Quinones as Neuroprotective Agents

“…It consists of a 1:2 mixture of coenzyme Q 10 with polyoxyethanyl α-tocopheryl sebacate (PTS), a self-emulsifying amphiphilic derivative of vitamin E (Figure 11). This formulation showed potent neuroprotective effects and was effective when delivered either prior or after neurotoxin exposure [48].…”

“…It consists of a 1:2 mixture of coenzyme Q10 with polyoxyethanyl α-tocopheryl sebacate (PTS), a self-emulsifying amphiphilic derivative of vitamin E (Figure 11). This formulation showed potent neuroprotective effects and was effective when delivered either prior or after neurotoxin exposure [48]. Beyond free radical scavenging, the neuroprotective effects of coenzyme Q 10 have been ascribed, at least in part, to Nrf2 induction due to the presence of electrophilic Michael acceptors in the quinone moiety [38,39].…”

Neuroprotective effects of coenzyme Q10 on neurological diseases: a review article

“…Water-soluble CoQ10 is not natural and can be prepared artificially. The natural CoQ10 is lipid-soluble (Wear et al, 2021). CoQ can inhibit mitochondrial fission and improve mitochondrial dynamics by decreasing Drp1 and Fis1 proteins (Li et al, 2017).…”

“…Currently, PD cannot be cured; however, neuroprotectants reduce the rate of neurodegeneration and improve the quality of life (Koller and Cersosimo, 2004). CoQ10 has shown neuroprotective activity in some neurodegenerative diseases, like PD (Mancuso et al, 2010;Wear et al, 2021). Screening for oxidative stress markers in patients with neurodegenerative disease, such as PD showed lower CoQ10 concentrations and higher lipoprotein oxidation levels in the cerebrospinal fluid, plasma, and brain cortex than in non-affected cases.…”