Purdue Researcher Repurposes Pair of FDA Approved Drugs to Treat a Rare Disease

Rare Daily Staff

Claudio Aguilar, a faculty member of the Purdue Institute for Cancer Research and the Purdue Institute for Drug Discovery, created the treatment method.

Lowe syndrome’s characteristic symptoms are a combination of anomalies that affect the eyes, kidneys and nervous system. The life span of a person affected by Lowe syndrome rarely extends beyond 40 years, with death often caused by kidney failure. Aguilar said treatments mostly address only the symptoms of Lowe syndrome rather than its causes.

The work is another example of how repurposing existing approved drugs can be a fast and cost-effective way of identifying new treatments for rare diseases with unmet needs.

Previous research in the Aguilar laboratory pointed to specific biochemical pathways that affect Lowe syndrome. The discovery led Aguilar to consider two FDA-approved drugs that modulate those pathways: rapamycin and a group of drugs called statins.

Rapamycin is approved as an anti-tumor drug. It prevents organ rejection after a kidney transplant because it decreases immune response. The investigator said it is in clinical trials for the treatment of polycystic kidney disease and has shown promise against Bardet-Biedl syndrome. Statins are a group of drugs that decrease the production of cholesterol in patients’ cells.

“Because we found levels of rapamycin’s target to be elevated in Lowe syndrome patients’ cells, it was an obvious choice for a therapeutic candidate,” Aguilar said. “Our results showed that Lowe syndrome patients’ cells exhibited a statistically significant reversion of phenotypes and a decrease in the abnormally high levels of the rapamycin’s activated target in comparison to the nontreated group.”

Statins, he noted, interfere with a biochemical pathway that also impacts the activation of an intracellular regulator that is hyperactivated in Lowe syndrome.

During tests that administered rapamycin and statins at the same dose as their original FDA-approved uses, Aguilar and his team observed the suppression of cellular phenotypes of Lowe syndrome and that patient cells started to behave as normal cells. He said statins and rapamycin complemented each other.

“For some patients, the administration of both drugs would be needed,” Aguilar said. “Nevertheless, further investigation is necessary to assess the mode and regime of application of these compounds to ameliorate Lowe syndrome manifestations in patients.”

Along with repurposing the FDA-approved drugs, Aguilar and his team are working on agents to target and reactivate an enzyme, called OCRL1, that is functionally deficient in people affected by Lowe syndrome.

Aguilar’s research has been funded with two grants from the National Institute of Diabetes and Digestive and Kidney Diseases, an institute of the National Institutes of Health. Additional support comes from the U.S.-based Lowe Syndrome Association, the U.K.-based Lowe Syndrome Trust, and the Clinical and Translational Sciences Institute.