October 25, 2016
By Mike Yeomans
A cross-disciplinary team of University of Pittsburgh researchers has demonstrated that a topical therapy applied prior to or after radiation exposure prevents skin damage in both animal and human models.
The results, published in the Journal of Investigative Dermatology, are expected to accelerate efforts to initiate clinical studies and license the technology, said Dr. Louis Falo, Chairman of the Department of Dermatology at the Pitt School of Medicine, and corresponding author for the study.
Falo joined the research team of Joel Greenberger, Professor and Chair of the Department of Radiation Oncology, and Peter Wipf, Distinguished University Professor of Chemistry, in 2008. Greenberger and Wipf had already been exploring treatments to mitigate radiation poisoning caused by an accident at a nuclear power facility or from a so-called “dirty bomb” device. Together they determined that the therapies being developed and investigated at Pitt would also potentially benefit the millions of people in the U.S. who undergo radiation therapy as a treatment for breast, head-and-neck, and other cancers.
“During the course of radiation therapy patients can develop cutaneous burns, which can be irritating and painful, diminishing their quality of life and potentially leading to dangerous infections,” Falo said. “Getting those burns can even disrupt their treatment regimen. What our results show is that topical treatment with this potent antioxidant can prevent skin damage at the source.”
Wipf, whose lab developed the molecule, said that it works by scavenging reactive oxygen and nitrogen species and thus preventing oxidative degradation processes in the cell and the mitochondria, thereby averting inflammation and cell death.
“This agent provides new treatment options for cancer patients undergoing a range of different radiation therapies, with the prospect for more simplified treatment regimens with improved quality of life post-treatment,” Wipf said.
Wipf said the credit for first synthesizing the molecule, called JP4-39, belongs to his former student, Joshua Pierce, who now operates his own lab at North Carolina State University, and for whom the molecule is named.
Results using human skin tissue clear path to clinical trials
Falo said he is optimistic for the therapy’s performance in clinical trials because the treatment appears to be effective in a model that uses human skin obtained from cosmetic procedures.
Funding to further de-risk the technology and develop a commercial strategy was provided by the Coulter Translational Partners program at Pitt. Coulter supported the preclinical studies that are specifically aimed at validating the efficacy of the molecule at clinically relevant dosing levels in order to pave the way for product formulation and clinical trials.
Max Fedor, Coulter Program Director, said, “This is an exciting therapeutic that has the potential to impact the outcome and quality of life for nearly 4.2 million cancer patients annually who undergo radiation therapy. Coulter selected this project because of its potential to reduce complications, enhance compliance, and significantly improve the patient experience during radiation treatment. This may be the first preventive and curative therapy for radiation dermatitis. We believe that the clinical and economic benefits of this technology will attract investment from the business community and support future clinical adoption.”
Falo, Greenberger and Wipf hold numerous patents and have developed several technologies that have been licensed or are available for licensing.
“The collaborators who developed this technology are a team of seasoned and prolific Pitt innovators, which gives us confidence that we will identify a strong licensing partner to bring this technology to market where it can have an impact on people’s lives,” said Alex Ducruet, Director of Licensing and Intellectual Property at the Innovation Institute.
Looking beyond treating radiation therapy, Falo is pursuing studies of the molecule’s ability to reduce skin damage from sun exposure, including the molecular changes that lead to skin cancer, as well as cosmetic applications related to wrinkling and normal skin aging.
“There are similarities in the underlying mechanisms associated with damage caused by therapeutic radiation and ultraviolet radiation exposure from the sun, including the oxidative stress that contributes to normal aging,” he said. “In ongoing studies we are investigating these other intriguing applications.”