An anticancer compound improved vision in zebrafish with genetically accelerated retinal degeneration: a single company's fourth "peer-reviewed" publication in four months
An anticancer compound improved vision in zebrafish with genetically accelerated retinal degeneration: a single company's fourth "peer-reviewed" publication in four months
On September 16, Telomir Pharmaceuticals published a preclinical study in IJMS reporting that Telomir-Zn, a compound originally developed as an anticancer drug, improved visual responses, restored retinal structure, and reduced oxidative stress over 14 days in zebrafish with artificially accelerated retinal degeneration. The company funded and designed the study itself.
Pentagrit Discovery, a contract laboratory in India, generated a zebrafish line whose retina degenerates on its own by 18 months of age. The fish carry a knockout of the wrn gene, the same gene whose loss of function in humans causes Werner syndrome, a premature aging disease marked by graying hair and cataracts by age twenty and death typically before fifty, combined with a mutation in the mitochondrial gene ND6, which encodes part of the cellular energy machinery. These fish lose photoreceptor cells, and their response to light lags by tens of seconds where a healthy fish responds almost instantly. The same zebrafish model was previously used in an independent study published in PNAS to test the anti-aging effects of sapanisertib.
A subset of the mutant fish were fed pellets containing Telomir-Zn for two weeks. At both doses, treated fish responded faster to light and to a moving object. Histological examination showed recovery of retinal thickness, and oxidative stress in the brain (measuring it directly in the adult zebrafish retina proved unfeasible, so the authors used a surrogate) dropped to near the levels seen in healthy animals. Over the two-week period, 17% of untreated mutants died compared to 0% of wild-type controls; mortality among treated fish was lower.
The company carried the mechanism over from its oncology work, where it had tested the compound in mice bearing prostate cancer and triple-negative breast cancer, the basis for its current FDA-authorized clinical protocol. The rationale: zinc in Telomir-Zn accumulates inside cells and displaces a fraction of the labile iron that, through the Fenton reaction, generates toxic oxygen radicals. It also suppresses iron-dependent demethylase enzymes that require this iron to function, altering gene activation and silencing patterns. A study published in Cell in August demonstrated the same principle: cells restrain reactive iron with polyamines, and without that restraint iron drives lipid peroxidation. The retinal target was chosen on the same logic: excess iron has long been linked to photoreceptor damage and age-related macular degeneration, one of the leading causes of vision loss in older adults.
DNA methylation was measured at two genomic loci by PCR, and the authors themselves describe the shift as "partial," without specifying its effect on retinal cell survival. Zinc and iron redistribution were measured in skin cells; this study contains no direct measurement of those metals in retinal cells.
All six authors are affiliated with Telomir Pharmaceuticals or its contract laboratories, with no independent co-authors, and the company is listed as a participant in study design. Over the preceding four months, the company published peer-reviewed papers on Wilson's disease, type 2 diabetes, prostate cancer, and triple-negative breast cancer using the same compound and the same "metal modulation" rationale, each accompanied by a press release. Immediately after the retinal publication, an analyst at the investment bank Maxim Group initiated coverage of the company's stock with a "buy" rating. "We see a common biology centered on intracellular metal balance and epigenetic regulation," said company CEO Erez Aminov, adding that this opens the prospect of applying Telomir-Zn to other cancers and, in time, to other diseases.