Developer Makes $10 Million Gift to Penn for Preclinical Development of RVCL Therapy

Rare Daily Staff

The Clayco Foundation, the philanthropic arm of the Chicago-based real estate development and construction firm, has made a $10 million gift to the University of Pennsylvania to accelerate development of a first-in-class therapy for retinal vasculopathy with cerebral leukoencephalopathy, a rare and fatal genetic disorder with no approved treatments.

The Clayco Foundation’s investment will enable IND-enabling studies to assess the drug’s safety profile—an essential step before entering human trials. The funding is particularly critical given the challenges of developing therapies for ultra-rare diseases, where limited patient populations often deter traditional investment.

The effort highlights the growing role of philanthropy in early-stage drug development, particularly for rare diseases that fall outside the commercial focus of large pharmaceutical companies.

“Without this kind of support, it would be extremely difficult to move a program like this forward,” said Jonathan Miner, an associate professor of rheumatology at Penn Medicine who is leading the effort. “We’re operating with far fewer resources than typical drug development efforts, but that flexibility has allowed us to pursue an innovative approach.”

Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) is caused by inherited mutations in the TREX1 gene and affects an estimated 200 patients worldwide. The condition leads to progressive damage of small blood vessels across multiple organs, including the brain, eyes, liver, and kidneys, ultimately resulting in organ failure. Patients typically begin experiencing symptoms in midlife, followed by rapid decline marked by vision loss, strokes, and cognitive impairment, with survival often limited to five to ten years after onset.

The funding will support preclinical safety studies of a novel small-molecule degrader being developed at the Perelman School of Medicine. The therapy is designed to selectively eliminate toxic proteins that drive the disease, potentially paving the way for human clinical trials.

The experimental therapy belongs to a growing class of targeted protein degraders, which work by recruiting the cell’s natural waste-disposal machinery. In this case, the small molecule binds both the mutated TREX1 protein and an E3 ligase—an enzyme that tags proteins for degradation—forcing the harmful protein into the cell’s “trash bin” while sparing its normal counterpart.

“This is a disease that affects so many organs across the body, so a typical targeted gene therapy doesn’t work,” said Miner. “We’ve developed a strategy that effectively labels abnormal proteins so the cell knows to destroy them.”

The approach has shown promising results in preclinical models. In mice engineered to carry the human TREX1 mutation, the degrader prevented organ damage and significantly improved survival, according to the research team.

The program is the result of a seven-year collaboration between Penn Medicine and chemists at the University of Michigan, led by Nouri Neamati, who designed and optimized the molecules. While Penn researchers evaluated biological effects, the Michigan team iterated on compound design to improve potency and selectivity.

“I watched this disease take the people I love, and I made a decision that no other family should have to feel powerless against it,” said Clayco Foundation Chairman Shawn Clark, whose mother and grandfather both died from RVCL. “There is nobody else leading the effort to find a treatment or a cure for RVCL, so we are going to be the ones to do it.”

If successful, the TREX1 degrader could represent not only the first disease-modifying treatment for RVCL, but also a broader proof of concept for using targeted protein degradation to treat systemic genetic disorders driven by toxic gain-of-function proteins.