New Compound Treats Blindness And Diabetes In Mice; Holds Potential For Possible Degenerative Disease Treatment In Humans
Meet KIRA6 — the result of four years of work, over a hundred separate experiments, and possibly the future of medication for degenerative diseases. The synthesized molecule is the brain child of researchers from University of California, San Francisco. In animal trials, the compound has helped mice with two distinct degenerative diseases both preserve cells and retain function.
Three Blind And Diabetic Mice
The mice in the study had either retinitis pigmentosa, a degenerative eye disease that eventually causes blindness, or a type of diabetes called Akita, which is characterized by the degeneration of beta-cells in the pancreas. The small molecule kinase inhibitor, KIRA6, prevented the destructive outbursts of cells of the animal subjects and halted the cell degeneration caused by the conditions.
Proved Proof Of Concept
“When we gave the drug over the time course of the study, we preserve significantly more cells,” Scott A. Oakes explained to Medical Daily. Although the researchers did not follow the progress of the mice long enough to call it an actual cure for the conditions, it did prove what co-author of the study, Feroz Papa, explained as proof of concept. “On the surface, these would seem to be two very different diseases, but IRE1-induced cell death is at the root of both,” Oakes said in a press release.
The study also helped the researchers to better understand the “ancient pathway,” called the unfolded protein response (UPR). When overwhelmed, the UPR will send signals to the cells to control stress levels. However, if the stress gets too great, cell death, or cell suicide, is then triggered. This is what occurred in the mice suffering from the two conditions.
Broader Implications
Curing lab mice is only the first step in a much bigger goal for the San Francisco-based researchers. “Our goal is to optimize the specificity of our compound, gather enough evidence so that we can test these in early stage clinical trials for humans,” Oakes said. While this is several years away, the findings of this study suggest that KIRA6 “does have potentially broad implications.”
Drug Developments
The researchers hope to eventually aid in the developments of drugs for a wide variety of conditions caused by cell degeneration. “We looked at two different disease, but there are many many more,” Papa told Medical Daily. Developing medication is a long process that takes many years, and it is likely that the end product may not resemble KIRA6 at all. It will, however, have similar properties. “Our eventual goal is to understand the science in greater detail and capitalize on what we have with KIRA6 to make it more drug-like,” Papa said.
Source: Oakes SA, Papa FR, Ghosh R, et al. Allosteric Inhibition of the IRE1α RNase Preserves Cell Viability and Function during Endoplasmic Reticulum Stress. Cell. 2014.