The Clayco Foundation has gifted $10 million to researchers at the Perelman School of Medicine at the University of Pennsylvania to help them to development a potential treatment for the ultra-rare disease retinal vasculopathy with cerebral leukoencephalopathy (RVCL)
“This is a disease that affects so many organs across the body, so a typical targeted gene therapy doesn’t work,” said Jonathan Miner, MD, PhD, an associate professor of Rheumatology at Penn, who leads the work. “We have developed something that labels abnormal proteins—just like you would a package. The body’s cells can then read that label and ship the protein to a specific location in the cell for destruction.”
RVCL is an inherited, autosomal dominant disease caused by mutations in a gene called TREX1 that affects around 200 people across the world. The mutation causes DNA damage and premature death of the endothelial cells that line small blood vessels. Over time, the surrounding tissue receives less blood and oxygen and begins to malfunction or die
People with the condition usually present in mid‑adulthood with slow vision loss from retinal vasculopathy and then develop stroke‑like episodes, cognitive decline, and psychiatric symptoms linked to white‑matter damage in the brain. There is no current disease-modifying treatment for the condition and people with the condition usually die in mid-late adulthood
Miner directs the RVCL Research Center at Penn. He and his team are working on several potential therapies for this very rare disease including the one funded by this donation, a small molecule drug candidate that can degrade damaged TREX1 proteins in the body
“In mice with the human mutation who get this disease, the degrader molecule saves their lives,” explained Miner in a press statement. “It stops organ damage and stabilizes them from further harms.”
The candidate therapy works by linking the faulty protein to an enzyme, an E3 ligase, that marks unwanted proteins so the cell can break them down. The damaged protein is then rapidly cleared by the cell’s disposal machinery, while normal proteins are spared
The $10 million donation from the Clayco Foundation will help Miner and colleagues move this drug candidate closer to the clinic
The Clayco Foundation is Chicago‑based and is closely linked to the design‑build firm Clayco, which was founded in the 1980’s by Bob Clark. Clark’s wife Ellen died of RVCL in 2010 and because of this the foundation has a strong focus on funding research that helps people with the condition
Miner and colleagues are also working on a couple of genetic therapies for RVCL using CRISPR and prime-editing technology. They are also assessing if crizanlizumab, a P‑selectin–blocking monoclonal antibody currently approved to reduce sickle cell crises, could be repurposed to also treat RVCL
News & FeaturesCRISPREnzymesMonoclonal antibody therapyMutationNeuropsychiatric symptomsOphthalmic diseasesRare diseases
