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Research
Neuronal Defense is an advanced nutritional pet supplement formulated to address the core pathophysiology of Canine Cognitive Dysfunction (CCD) – a condition characterized by progressive oxidative damage and bioenergetic failure within critical neural circuits.

Focusing on the oxidative stress and bioenergetic decline caused in senior dogs associated with CCD, SoluPet’s highly bioavailable formula offers a targeted intervention that integrates seamlessly into any veterinarian’s care plan for their geriatric patients.

The active ingredient

Neuronal Defense’s key active ingredient, Coenzyme Q10 (CoQ10), is a natural compound responsible for boosting cellular energy levels in mitochondria and converting nutrients into essential energy that neurons need to function optimally.

Dog's endogenous levels of CoQ10 tend to decline with age. The primary challenge in bridging this gap has been the well-documented absorption limitations of conventional CoQ10 supplements. Standard forms of CoQ10 have an exceptionally low aqueous solubility of approximately less than 1.0mg/L, thus leading to inadequate absorption, negligible systemic delivery, and failure to achieve therapeutic levels of active ingredients in the bloodstream.

What makes Neuronal Defense different?

To overcome this hurdle, Neuronal Defense utilizes a unique, self-emulsifying form of Vitamin E – Polyoxyethanyl-α-tocopheryl sebacate (PTS). This naturally occurring compound encapsulates CoQ10 into soluble micelles and is designed to maximize intestinal absorption and create a bioavailable delivery complex that transports CoQ10 to target tissues such as the brain.

This breakthrough technology in Neuronal Defense has seen the solubility of CoQ10 jump to 6,666 mg/L. Research also shows that animals given water containing Neuronal Defense showed a time-dependent rise in their CoQ10 levels, reaching approximately 35% above the initial baseline three hours after the first dosage.

Once absorbed, the combination of CoQ10 and the integral Vitamin E from PTS work together to neutralize free radicals, directly countering the oxidative stress that is a primary driver of neuronal damage.

On the offense

Neuronal Defense’s unique formulation of CoQ10 fights harmful molecules, but also plays a vital role in the mitochondrial electron transport chain. It acts as a crucial component in the production of adenosine triphosphate (ATP), which facilitates healthy cognitive function and maintains neuronal vitality. 

The proof

Study One: 

Orally delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson’s disease.

Muthukumaran K, Leahy S, Harrison K, Sikorska M, Sandhu JK, Cohen J, Keshan C, Lopatin D, Miller H, Borowy-Borowski H, Lanthier P, Weinstock S, Pandey S. Orally delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson's disease. BMC Neurosci. 2014 Jan 31;15:21. doi: 10.1186/1471-2202-15-21. Erratum in: BMC Neurosci. 2021 Dec 20;22(1):79. doi: 10.1186/s12868-021-00684-7. PMID: 24483602; PMCID: PMC3917573.
https://pubmed.ncbi.nlm.nih.gov/24483602/

Abstract

Paraquat, still used as an herbicide in some parts of the world, is now regarded as a dangerous environmental neurotoxin and is linked to the development of Parkinson's disease (PD). Paraquat interacts with cellular redox systems and causes mitochondrial dysfunction and the formation of reactive oxygen species, which in turn, plays a crucial role in the pathophysiology of PD. Various antioxidant therapies have been explored with the expectations that they deliver health benefits to the PD patients, however, no such therapies were effective. Here we have tested the neuroprotective efficacy of a novel water-soluble CoQ10 (Ubisol-Q10), in a rat model of paraquat-induced neurodegeneration in order to evaluate its potential application in the management of PD.

Results

We have developed a rat model of progressive nigrostriatal degeneration by giving rats five intraperitoneal injections of paraquat (10 mg/kg/injection), once every five days. Neuronal death occurred over a period of 8 weeks with close to 50% reduction in the number of tyrosine hydroxylase-positive cells. Ubisol-Q10, at 6 mg CoQ10/kg body weight/day, was delivered as a supplement in drinking water. The intervention began after the completion of paraquat injections when the neurodegenerative process had already begun and about 20% of TH-positive neurons were lost. Ubisol-Q10 treatment halted the progression of neurodegeneration and remaining neurons were protected. The outcomes were evaluated based on the number of surviving tyrosine hydroxylase-positive neurons in the substantia nigra region and improved motor skills in response to the Ubisol-Q10 intervention. To maintain this neuroprotection, however, continuous Ubisol- Q10 supplementation was required, if withdrawn, the neuronal death pathway resumed, suggesting that the presence of CoQ10 was essential for blocking the pathway.

Conclusion

The CoQ10, given orally as Ubisol-Q10 in drinking solution, was effective in blocking the progression of neurodegeneration when administered therapeutically (post-toxin injection), at a much lower concentration than other previously tested oil soluble formulations and well within the acceptable daily intake of 12 mg/kg/day. Such unprecedented neuroprotection has never been reported before. These results are very encouraging and suggest that Ubisol-Q10 should be further tested and developed as a therapy for halting the progression of PD. 

The treatment protected the remaining neurons and improved motor skills, but this neuroprotective effect required continuous supplementation to be maintained. The study concludes that Ubisol-Q10 has strong potential as a therapeutic intervention for blocking the progression of Parkinson's disease.

Study Two: 

Ubisol-Q10 (a Nanomicellar Water-Soluble Formulation of CoQ10) Treatment Inhibits Alzheimer-Type Behavioral and Pathological Symptoms in a Double Transgenic Mouse (TgAPEswe, PSEN1dE9) Model of Alzheimer’s Disease.

Muthukumaran K, Kanwar A, Vegh C, Marginean A, Elliott A, Guilbeault N, Badour A, Sikorska M, Cohen J, Pandey S. Ubisol-Q10 (a Nanomicellar Water-Soluble Formulation of CoQ10) Treatment Inhibits Alzheimer-Type Behavioral and Pathological Symptoms in a Double Transgenic Mouse (TgAPEswe, PSEN1dE9) Model of Alzheimer's Disease. J Alzheimers Dis. 2018;61(1):221-236. doi: 10.3233/JAD-170275. PMID: 29154270.
https://pubmed.ncbi.nlm.nih.gov/29154270/ 

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology. Previously, we have shown that a water-soluble formulation of Coenzyme Q10 (Ubisol-Q10), an integral part of the electron transport chain, stabilizes mitochondria and prevents neuronal cell death caused by neurotoxins or oxidative stress both in vitro and in vivo. In this study, we evaluated the neuroprotective effects of Ubisol-Q10 treatment in double transgenic AD mice. In the present study, we report that providing Ubisol-Q10 in drinking water (at a dose of ∼6 mg/kg/day) reduced circulating amyloid-β (Aβ) peptide, improved long term memory, preserved working spatial memory, and drastically inhibited Aβ plaque formation in 18-month-old transgenic mice compared to an untreated transgenic group. Thus Ubisol-Q10 supplementation has the potential to inhibit the progression of neurodegeneration, leading to a better quality of life for humans suffering with AD.

Conclusion

Ubisol-Q10 treatment in a transgenic mouse model of Alzheimer's disease significantly reduced circulating amyloid-β peptide and drastically inhibited the formation of amyloid plaques in the brain. The therapy also preserved cognitive function, improving long-term memory and working spatial memory in the treated mice. The study concludes that Ubisol-Q10 supplementation has strong potential to inhibit the progression of neurodegeneration and improve outcomes in Alzheimer's disease.

Study Three: 

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.

Sikorska M, Lanthier P, Miller H, Beyers M, Sodja C, Zurakowski B, Gangaraju S, Pandey S, Sandhu JK. 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. Neurobiol Aging. 2014 Oct;35(10):2329-46. doi: 10.1016/j.neurobiolaging.2014.03.032. Epub 2014 Apr 2. PMID: 24775711; PMCID: PMC4892899.
https://pubmed.ncbi.nlm.nih.gov/24775711/ 

Abstract

Although the support for the use of antioxidants, such as coenzyme Q(10) (CoQ(10)), 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 CoQ(10) is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ(10) (Ubisol-Q(10)) 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-Q(10) was delivered in drinking water. Prophylactic application of Ubisol-Q(10), started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q(10) group by day 28). Therapeutic application of Ubisol-Q(10), 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-Q(10) concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ(10)/kg body weight/day, showing clearly that high doses of CoQ(10) were not required to deliver these effects. Furthermore, the Ubisol-Q(10) 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-Q(10) was capable of halting the neurodegeneration already in progress; however, to maintain it a continuous supplementation of Ubisol-Q(10) 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-Q(10) 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.

Conclusion

In a mouse model of Parkinson's disease, the nanomicellar formulation Ubisol-Q10 demonstrated a robust capacity to halt ongoing neurodegeneration, preserving dopamine neurons and motor function even when administered after the toxic insult had begun. This neuroprotective effect was achieved with low doses and was critically dependent on continuous supplementation, with evidence suggesting astroglia play a key role in the mechanism. The study concludes that Ubisol-Q10 is a highly promising candidate for further clinical investigation as an adjuvant therapy for Parkinson's disease.

Other studies

Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer’s Disease

Sharma C, Kim S, Nam Y, Jung UJ, Kim SR. Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer's Disease. Int J Mol Sci. 2021 May 3;22(9):4850. doi: 10.3390/ijms22094850. PMID: 34063708; PMCID: PMC8125007.
https://pubmed.ncbi.nlm.nih.gov/34063708/ 

Abstract

Alzheimer's disease (AD) is the most frequent cause of age-related neurodegeneration and cognitive impairment, and there are currently no broadly effective therapies. The underlying pathogenesis is complex, but a growing body of evidence implicates mitochondrial dysfunction as a common pathomechanism involved in many of the hallmark features of the AD brain, such as formation of amyloid-beta (Aβ) aggregates (amyloid plaques), neurofibrillary tangles, cholinergic system dysfunction, impaired synaptic transmission and plasticity, oxidative stress, and neuroinflammation, that lead to neurodegeneration and cognitive dysfunction. Indeed, mitochondrial dysfunction concomitant with progressive accumulation of mitochondrial Aβ is an early event in AD pathogenesis. Healthy mitochondria are critical for providing sufficient energy to maintain endogenous neuroprotective and reparative mechanisms, while disturbances in mitochondrial function, motility, fission, and fusion lead to neuronal malfunction and degeneration associated with excess free radical production and reduced intracellular calcium buffering. In addition, mitochondrial dysfunction can contribute to amyloid-β precursor protein (APP) expression and misprocessing to produce pathogenic fragments (e.g., Aβ1-40). Given this background, we present an overview of the importance of mitochondria for maintenance of neuronal function and how mitochondrial dysfunction acts as a driver of cognitive impairment in AD. Additionally, we provide a brief summary of possible treatments targeting mitochondrial dysfunction as therapeutic approaches for AD.

Conclusion

The study concludes that mitochondrial dysfunction is a central pathogenic driver of Alzheimer's disease, contributing directly to hallmark pathologies like amyloid plaques and neurofibrillary tangles. This dysfunction impairs energy production, increases oxidative stress, and disrupts critical neuronal functions, ultimately leading to synaptic failure and cognitive decline. Therefore, therapeutic strategies aimed at improving mitochondrial health represent a promising avenue for treating Alzheimer's disease.

Coenzyme Q10 and cognition in atorvastatin treated dogs

Martin SB, Cenini G, Barone E, Dowling AL, Mancuso C, Butterfield DA, Murphy MP, Head E. Coenzyme Q10 and cognition in atorvastatin treated dogs. Neurosci Lett. 2011 Aug 26;501(2):92-5. doi: 10.1016/j.neulet.2011.06.054. Epub 2011 Jul 8. PMID: 21763754; PMCID: PMC3174091.
https://pubmed.ncbi.nlm.nih.gov/21763754/ 
Abstract

Statins have been suggested to protect against Alzheimer's disease (AD). Recently, however, we reported that aged dogs that underwent chronic statin treatment exhibited cognitive deficits compared with age matched controls. In human studies, blood levels of Coenzyme Q10 (CoQ10) decrease with statin use. CoQ10 is important for proper mitochondrial function and is a powerful antioxidant, two important factors for cognitive health in aging. Thus, the current study tested the hypothesis that CoQ10 levels in the serum and/or parietal cortex are decreased in statin treated dogs and are associated with poorer cognition. Six aged beagles (>8 years) were administered 80 mg/day of atorvastatin for 14.5 months and compared with placebo-treated animals. As predicted, serum CoQ10 was significantly lower in statin-treated dogs. Parietal cortex CoQ10 was not different between the two groups. However, poorer cognition was correlated with lower parietal cortex CoQ10. This study in dogs suggests that serum CoQ10 is reduced with atorvastatin treatment. CoQ10 levels in the brain may be linked to impaired cognition in response to atorvastatin, in agreement with previous reports that statins may have a negative impact on cognition in the elderly.

Conclusion

The study concludes that chronic atorvastatin treatment in aged dogs significantly reduces serum CoQ10 levels. Although statin treatment did not directly lower brain CoQ10, poorer cognitive performance was strongly correlated with lower CoQ10 levels in the parietal cortex. These findings suggest that statin-associated cognitive impairment may be mediated by compromised CoQ10 status in the brain.

In Vitro Research:

*The information on this page is intended solely for use by veterinary professionals.  It is for informational purposes only and not a substitute for independent professional medical judgment, expertise, or clinical decision-making.  Veterinarians are responsible for evaluating the applicability of any information for their patients and exercising appropriate clinical judgment.  Nothing on this page constitutes medical advice, diagnosis, treatment, or an endorsement of any specific therapeutic approach.  If you are not a veterinary professional, you should not rely on this information and should discuss any questions about the information on this page with your Veterinary professional.

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