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Selected Research Abstracts of Studies on CAN-C Eye Drops 

What Evidence Exists that CAN-C Drops are Effective for Dogs (and Humans)?

                                 

Important Note: We have listed several abstracts of Dr. Mark Babizhayev's research publications and the effects of N-acetylcarnosine lubricant eye drops for dogs and humans. For a review of all publications regarding the treatment of cataracts with Can-C eye drops, please visit the following public medical database resource:

www.pubmed.com

Once you have landed on the public med website simply type in Dr. Babizhayev's last name only (Babizhayev) into the search field at the top of the page. You will access all of the available publications on this exciting breakthrough in the non-surgical treatment of cataracts.

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Vet Ophthalmol. 2006 Sep-Oct;9(5):311-6.

The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Williams DL, Munday P.

Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 OES, England, UK. doctordlwilliams@aol.com

OBJECTIVE: To determine the efficacy of a topical antioxidant formulation including N-acetyl carnosine in the treatment of canine cataract in a preliminary nonplacebo, controlled, unmasked study.

ANIMALS STUDIED: Thirty dogs of varying breeds and ages with a spectrum of lens opacities ranging from nuclear sclerosis to total mature cataract.

METHODS: Dogs were treated three times daily with topical 2% N-acetyl carnosine in a buffered vehicle containing the antioxidants glutathione, cysteine ascorbate, L-taurine and riboflavin. Dogs were examined prior to treatment and at 2, 4 and 8 weeks during treatment, by direct and indirect ophthalmoscopy and slit-lamp biomicroscopy after pharmacologic pupil  dilation. Photographic documentation of lens opacity was achieved by retroillumination photography, with three photographs taken at each examination  time-point. A lens opacification index (LOI), determined by integration of the grayscale level of each pixel across the image, was evaluated by computerized image analysis of digitized images. Alteration in mean LOI was determined for each animal, having normalized the initial LOI.

RESULTS: Fifty-eight eyes of 30 dogs were evaluated, 22 with mature cataract, 13 with immature cataract, 9 with cataract associated with other intraocular disease such as uveitis and 14 with nuclear sclerosis alone. One dog was unilaterally anophthalmic after previous enucleation and one had a phthytic eye after previous uveitis-induced glaucoma. Image analysis showed a reduction in mean LOI in all cataract groups (mean resolution in opacity of 2.3 +/-  0.33% for all cataracts), although this was only statistically significant in those eyes with immature cataract (mean resolution of opacity 4.5 +/-  0.33%) or nuclear sclerosis (mean decrease in opacity 5 +/- 0.37%). Reduction in lens opacity was seen in eyes with mature cataract (0.5 +/- 0.4%) and in miscellaneous cataract associated with intraocular inflammation (1.3 +/- 0.4%), but these changes were not statistically significant. Owner evaluation of visual capability, however, suggested improvement in vision in 80% of cases by the end of the study.

CONCLUSIONS: This study demonstrates some marginal reduction in lens opacification in a substantial number of cases of canine cataract with the use of a topical nutritional antioxidant

formulation including N-acetyl carnosine. Lens opacification was improved with treatment in eyes with immature cataract or nuclear sclerosis while in eyes with mature cataract or cataract with associated intraocular inflammatory pathology less reduction was seen.

 

Drugs R D. 2004;5(3):125-39.

Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes.
Babizhayev MA, Deyev AI, Yermakova VN, Brikman IV, Bours J.

Cataract formation represents a serious problem in the elderly, with approximately 25% of the population aged >65 years and about 50% aged >80 years experiencing a serious loss of vision as a result of this condition. Not only do cataracts diminish quality of life, they also impose a severe strain on global healthcare budgets. In the US, 43% of all visits to ophthalmologists by Medicare patients are associated with cataract. Surgery represents the standard treatment of this condition, and 1.35 million cataract operations are performed annually in the US, costing 3.5 billion US dollars (year of  costing, 1998). Unfortunately, the costs of surgical treatment and the fact that the number of patients exceeds surgical capacities result in many patients being blinded by cataracts worldwide. This situation is particularly serious in developing countries; worldwide 17 million people are blind because of cataract formation, and the problem will grow in parallel with aging of the population.

In any event, surgical removal of cataracts may not represent the optimal solution. Although generally recognised as being one of the safest operations, there is a significant complication rate associated with this surgical procedure. Opacification of the posterior lens capsule occurs in 30-50% of patients within 2 years of cataract removal and requires laser treatment, a further 0.8% experience retinal detachments, approximately 1% are rehospitalised for corneal problems, and about 0.1% develop endophthalmitis. Although the risks are small, the large number of procedures performed means that 26,000 individuals develop serious complications as a result of cataract surgery annually in the US alone. Thus, risk and cost factors drive the investigation of pharmaceutical approaches to the maintenance of lens transparency.

The role of free radical-induced lipid oxidation in the development of cataracts has been identified. Initial stages of cataract are characterised by the accumulation of primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in later stages there is a prevalence of LPO

fluorescent end-products. A reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end-product

accumulation in its tissue, accompanied by sulfhydryl group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It is concluded that peroxide damage of the lens fibre

membranes may be the initial cause of cataract development.

N-acetylcarnosine (as the ophthalmic drug Can-C), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye in the form of Can-C, N-acetylcarnosine functions as a time-release prodrug form of L-carnosine resistant to hydrolysis with carnosinase. N-acetylcarnosine has potential as an in vivo universal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular

turnover into L-carnosine. In our study the clinical effects of a topical solution of N-acetylcarnosine (Can-C) on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed that N-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes.

Drugs R D. 2002;3(2):87-103.

Efficacy of N-acetylcarnosine in the treatment of cataracts.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Doroshenko VS, Zhukotskii AV, Goldman IM.

PURPOSE: To evaluate the effects of 1% N-acetylcarnosine (NAC) solution on lens clarity over 6 and 24 months in patients with cataracts. TRIAL DESIGN: Randomised, placebo-controlled study. PARTICIPANTS: 49 subjects (76 affected eyes) with an average age of 65.3 +/- 7.0 years with a diagnosis of senile cataract with minimum to advanced opacification in various lens layers.

METHODS: 26 patients (41 eyes) were allocated to topical NAC 1% eyedrops twice daily. The control group consisted of 13 patients (21 eyes) who received placebo eyedrops and 10 patients (14 eyes) who did not receive eyedrops.

MAIN OUTCOME MEASURES: All patients were evaluated at entry and followed up every 2 months for a 6-month period (trial 1), or at 6-month intervals for a 2-year period (trial 2), for best-corrected visual acuity and glare testing. In addition, cataract was measured using stereocinematographic slit-images and retro-illumination examination of the lens. Digital analysis of lens images displayed light scattering and absorbing centres in two- and three-dimensional scales.

RESULTS: The overall intra-reader reproducibility of cataract measurements (image analysis) was 0.830, and glare testing 0.998. After 6 months, 90% of NAC-treated eyes showed improvement in best corrected visual acuity (7 to 100%) and 88.9% showed a 27 to 100% improvement in glare sensitivity. Topographic studies indicated fewer areas of posterior subcapsular lens opacity and 41.5% of treated eyes had improvement in image analysis characteristics. The overall ratios of image analysis characteristics at 6 months compared with baseline measures were 1.04 and 0.86 for the control and NAC-treated group, respectively (p < 0.001). The apparent benefits of treatment were sustained after 24 months' treatment. No treated eyes demonstrated worsening of vision. The overall visual outcome in the control group showed significant worsening after 24 months in comparison with both baseline and the 6-month follow-up examination. The overall clinical results observed in the NAC-treated group by the 24-month period of examination differed significantly (p < 0.001) from the control group in the eyes with cortical, posterior subcapsular, nuclear or combined lens opacities. Tolerability of NAC eyedrops was good in almost all patients, with no reports of ocular or systemic adverse effects.

CONCLUSION: Topical NAC shows potential for the treatment and prevention of cataracts.


Clin 96 Oct 15;254(1):1-21.Chim Acta. 19
Erratum in: Clin Chim Acta 1997 Mar 18;259(1-2):199-201.

N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant.
Babizhayev MA, Yermakova VN, Sakina NL, Evstigneeva RP, Rozhkova EA, Zheltukhina GA.
Moscow Helmholtz Research Institute of Eye Diseases, Russian Federation.

The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders, which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).

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