Key Takeaways
- Telomir-Zn improved measures of visual function and retinal-layer structure after 14 days of treatment in a preclinical zebrafish model of age-related retinal degeneration
- Treatment reduced measures of oxidative stress and was associated with changes in relative telomeric DNA content, DNA methylation, intracellular iron, and iron-dependent histone demethylase activity
Telomir Pharmaceuticals announced the publication of preclinical findings showing that Telomir-Zn improved visual function and retinal structure while reducing oxidative stress in a zebrafish model of mitochondrial dysfunction and age-related retinal degeneration.
The peer-reviewed study, published in the International Journal of Molecular Sciences, also identified changes in intracellular metal homeostasis, DNA methylation, and relative telomeric DNA content following treatment. The findings remain preclinical, and Telomir’s clinical development program for Telomir-Zn is currently focused on oncology.
Untreated animals in the accelerated retinal degeneration model demonstrated substantial visual impairment, photoreceptor loss, retinal pigment epithelium disruption, and degeneration across multiple retinal layers. Following 14 days of oral Telomir-Zn treatment, investigators reported significant improvements in central visual response, moving-object tracking, and adaptation to changes in light intensity.
Histological analyses also showed improvements in retinal degeneration, including restoration of thickness in the outer and inner nuclear layers, outer plexiform layer, and ganglion cell layer.
The researchers additionally evaluated oxidative stress associated with mitochondrial dysfunction. Telomir-Zn significantly reduced brain reactive oxygen species, which investigators used as a surrogate measure of mitochondrial oxidative stress. At the higher dose studied, reactive oxygen species levels moved toward those observed in wild-type animals.
Complementary experiments in human ARPE-19 retinal pigment epithelial cells showed that Telomir-Zn dose-dependently attenuated iron- and copper-induced calcium dysregulation and reduced copper-induced intracellular reactive oxygen species toward baseline.
Investigators also examined markers associated with aging and genomic regulation. Relative telomeric DNA content was significantly lower in the retinal degeneration model than in healthy wild-type animals. Telomir-Zn treatment was associated with a dose-dependent increase in relative telomeric DNA content toward the wild-type profile. Treatment was also associated with restoration of altered DNA methylation patterns at selected aging-associated CpG loci.
According to the researchers, these findings raise the possibility that the compound’s activity extends beyond its effects on oxidative stress to genomic and epigenetic processes associated with cellular aging and degeneration. Further studies will be needed to establish the relevance of these findings to human AMD.
“This study gives us an important new view of the relationship between intracellular metal balance, oxidative stress, epigenetic regulation and retinal degeneration,” Itzchak Angel, PhD, chief scientific advisor of Telomir, said in the company announcement.
Telomir said its clinical development efforts remain centered on oncology. Telomir-Zn is advancing under an FDA-cleared investigational new drug application for a phase 1/2 study in patients with advanced or metastatic triple-negative breast cancer.
The retinal study, “Targeted Intracellular Metal Modulation Attenuates Oxidative Stress and Preserves Retinal Integrity and Function in a Zebrafish Model of Mitochondrial Dysfunction and Age-Related Retinal Degeneration,” was published in International Journal of Molecular Sciences (2026;27[18]:8265; doi:10.3390/ijms27188265).
