Scarring, or fibrosis, can lead to organ failure and is the end stage of many diseases, including lung, liver and heart disease. Before coming to MUSC, Carol Feghali-Bostwick, Ph.D., the Kitty Trask Holt Endowed Chair for Scleroderma Research and a professor of medicine, identified antifibrotic properties of a peptide that not only stopped fibrosis but reversed it in mice and cultured human tissue.
The peptide was licensed to iBio Inc., a biologics company that develops therapeutics in plants. Since then, iBio has been producing the protein using a plant-based system. In November 2020, MUSC, iBio and Novici Biotech received a U.S. patent on plant-based production for the peptide that is being developed by iBio. This novel production method is inexpensive and should ensure an adequate supply of the peptide for clinical trials and later for clinical use.
Since coming to MUSC almost eight years ago, Feghali-Bostwick has continued to perform extensive studies to determine the effectiveness of the peptide.
“The peptide that we generated was sort of an accidental discovery,” said Feghali-Bostwick. “We stumbled upon it when we were actually looking for factors that induce fibrosis.”
“As scientists, we all dream of this. We all do research because we want to make a difference in improving the lives of people.”
Dr. Carol Feghali-Bostwick
The peptide is derived from an endostatin, a molecule that occurs naturally in the body and is responsible for inhibiting the growth of blood vessel linings. Since endostatins are naturally present in humans, the antifibrotic peptide is not expected to cause adverse effects. “As scientists, we all dream of this,” said Feghali-Bostwick. “We all do research because we want to make a difference in improving the lives of people.”
Not only has Feghali-Bostwick’s team tested the function of the peptide in mice, but they have also developed a technology for maintaining fibrotic lung and skin tissue in the laboratory. Feghali-Bostwick believes that testing the peptide in these tissues can closely mimic how the peptide would act in the human body. As in mice, the peptide reduced fibrosis in the isolated lung and skin tissue.
“Our peptide seems to affect multiple targets that we know promote fibrosis,” explained Feghali-Bostwick. “And this is why we think it is effective not just at blocking fibrosis but also at reversing some established fibrosis.”
In fibrosis, many mechanisms cause uncontrolled wound healing and scar tissue. Currently available medications are insufficient because they target only one mechanism, leaving several others still active. The endostatin peptide, however, is able to target several of these pathways, effectively targeting fibrosis.
If the peptide proves safe and effective in clinical trials and is approved by the U.S. Food and Drug Administration, it could help many patients, since fibrosis is the end stage of many diseases.
“We want to get this to as many people as possible,” said Feghali-Bostwick. “We want to make sure it’s affordable so anyone who has the condition can have access to it.”
“Our peptide seems to affect multiple targets that we know promote fibrosis. This is why we think it is effective not just at blocking fibrosis but also at reversing some established fibrosis.”
Dr. Carol Feghali-Bostwick
That is why iBio uses a plant-based system, plant molecular farming, to produce the peptide. The mass production of peptides in that system is cost-effective, efficient and rapid. Feghali-Bostwick and her team showed that the plant-based product is effective at reducing fibrosis in the fibrotic lungs and skin tissue they had used in the initial studies of the peptide.
At MUSC, Feghali-Bostwick and her team have developed assays that compare the activity of the peptides produced in different batches. They have also developed a marker the levels of which can be tracked in the mouse serum to determine the effectiveness of the peptide.
The next step for the peptide is a phase I clinical trial in patients with scleroderma, an autoimmune disease in which fibrosis affects the skin and multiple internal organs and thus acts as a prototypic disease for fibrosis. “
“If it works in a prototypic disease with fibrosis in different organs, it will likely work on fibrotic diseases affecting specific organs,” said Feghali-Bostwick.