Imidazole-containing peptidomimetic NACA as a potent drug for the medicinal treatment of age-related cataract in humans

The objective of this manuscript is to test the efficacy of N-alpha-acetylcarnosine for the treatment of senile cataract in humans. It was designed as a randomized controlled trial. Forty-nine subjects--volunteers (76 eyes) with an average age of 65.3 +/- 7.0 years were enrolled and randomized into two groups at diagnosis of senile cataract. Changes in lens clarity were measured and quantitated over 6 to 24 months thereafter. Patients administered 1% N-alpha-acetylcarnosine (NACA) (26 patients, 41 eyes = Group II), placebo composition (13 patients, 21 eyes) topically (two drops, twice daily) to the conjunctival sac, or were untreated (10 patients, 14 eyes); two latter groups of patients were combined into the control (reference) group I. Patients were evaluated upon entry, at every 2-month (Trial 1) and 6-month (Trial 2) intervals for best corrected visual acuity (b/c VA), by ophthalmoscopy, original techniques of glare test (Trial I), stereocinematographic slit-image and retro-illumination photography with subsequent interactive digital image analysis and 3D computer graphics of the lens light scattering/absorbing centers. The intra-reader reproducibility of measuring techniques for cataractous changes was good with the overall average of correlation coefficients for image analytical data 0.830 and glare test readings 0.998. Group I of patients demonstrated the variability in densitometric readings of lens cloudings, negative advance in glare sensitivity over 6 months, and gradual deterioration of VA and gross transmissivity of lenses over 24 months comparatively to baseline and the 6-month follow-up examinations. As compared with baseline examination, over 6 months 41.5% of the eyes treated with NACA presented a significant improvement of the gross transmissivity degree of lenses, 90.0% of the eyes showed a gradual improvement in VA to 7-100% and 88.9% of the eyes ranged a 27-100% improvement in glare sensitivity. Topographic study demonstrated less density and corresponding areas of opacification in posterior subcapsular and cortical morphological regions of the lens consistent with VA up to 0.3. The total study period over 24 months revealed that the beneficial effect of NACA is sustainable. No cases resulted in a worsening of VA and image analytical readings of lenses in the NACA-treated group of patients. In most of the patients drug tolerance was good. Statistical analysis revealed the significant differences over 6 and 24 months in cumulative positive changes of overall characteristics of cataracts in the NACA-treated group II from the control group I. The N-acetylated imidazole-containing peptidomimetic NACA is proposed as an effective and physiologically acceptable drug for nonsurgical treatment of age-related and senile cataracts.