Pitt and UPMC Enterprises, through its Translational Sciences division, are collaborating again to provide funding support for therapeutics projects that need further de-risking experiments to enhance their clinical and commercial potential. We are featuring a project that received funding from the most recent proposal request.
Kidney Disease Therapy Research Gets Boost from OIE Collaboration with UPMC Enterprises
In less than the time it takes to watch an episode of Jeopardy, your kidneys will have filtered your entire blood supply, removing waste and excess water.
For people suffering from early-stage disease of these critical organs, there are no therapies beyond bed rest. For more advanced diseases, machine filtration known as dialysis is required, and once begun often results in a significantly shortened lifespan. A final option is a transplant, which is also fraught with short and long-term risks, including a lack of donated kidneys resulting in wait times of five years or more.
Neil Hukriede, professor in the Department of Cell Biology, discovered his first therapeutic molecule to potentially drive a functional recovery from kidney disease and reduce scarring in 2010. Still, that molecule was easily metabolized in the body, eliminating it as a good candidate for further development.
Today, thanks to a collaboration with an elite pharmacological chemist, and his lab’s development of human kidney organoids derived from induced pluripotent stem cells that can be used to accelerate the screening of potential therapies, Hukriede stands at the threshold of potentially bringing a viable therapeutic to the clinic sometime in the next 3-5 years.
Catalyzing the next phase of his quest to make an impact on the nearly 40 million people suffering kidney disease in the U.S. is a grant he received from the Translational Sciences division of UPMC Enterprises, the commercialization arm of the UPMC Health System.
“With this partnership, UPMC Enterprises has stepped up to help fill a clinical need that has not been addressed for people suffering from kidney disease,” Hukriede said.
Key to Hukriede’s progress toward developing a drug that goes where it’s supposed to in the kidney and resists being absorbed by the body before it can carry out its therapeutic effect is the collaboration he formed with Donna Huryn.
Huryn is a medicinal chemist who began her career in the pharmaceutical industry. She served as a professor at the Pitt School of Pharmacy until last year when she joined the University of Pennsylvania as a professor of practice in the chemistry department.
“Donna is a world-class medicinal chemist. She understands what it takes to make a compound that can get into the clinic. We discover things all the time, but finding something that will make it through clinical trials for safety and efficacy is extremely difficult, and where Donna excels,” Hukriede said.
Huryn is also collaborating with Ed Burton, Pitt professor in the Department of Neurology, on creating a class of molecules that can treat progressive supranuclear palsy (PSP). This effort also received funding from UPMC-E Translational Sciences last year.
“Our team has been researching the kidney disease space for some time and flagged it as an area of high unmet need for the 2023 RFP after assessing the market landscape and clinical-stage pipeline,” said Matthias Kleinz, EVP and head of the Translational Sciences Team.
“Our team has prioritized searching for novel therapies with the potential to help these patients, and we were thrilled to learn of Neil and Donna’s work. Their drug has the chance to be best-in-class, with preclinical data showing that it not only slows the progression of kidney disease but could reverse fibrosis, giving patients a much better outlook for recovering from the disease. It’s been great working with Neil and Donna, and we look forward to the work we’ll do together in the coming years to bring this therapy to patients.”
In the first year of funding, Hukriede and Huryn’s goal is to screen for compounds that show increased rate of renal recovery and decreased fibrosis (scarring). Then, in the second year the focus will shift to demonstrating the safety profile and efficacy in the human organoid models.
If all goes well, a compound could approach readiness for human testing in 3-5 years, Hukriede said.
The accelerated development timeline for potential new compounds is directly attributable to the use of the stem cell derived kidney organoids that have the form, including vasculature, of a human kidney. The potential for organoids to revolutionize the drug discovery process was a significant impetus behind the creation of the new Center for Integrative Organ Systems at Pitt by Anantha Shekhar, Senior Vice Chancellor for the Health Sciences and Dean of the School of Medicine.
He tasked Hukriede with leading this new center, which is underpinning the translation of personalized regenerative medicine discoveries to therapies in the clinic. The center is designed to allow investigators to use several model systems (e.g., organoids/zebrafish/mouse) that allow them to understand similarities and differences of how organs respond in many models of injury. Since there are induced pluripotent stem cell (iPSC) models for virtually every organ in the human body, this will allow a “whole system” field to emerge, enabling investigators unprecedented opportunities to conduct systematic drug screens that can be tailored to individual patients and unique populations.
Pitt and UPMC Enterprises Translational Sciences are supporting a new funding opportunity for transformative therapeutics in specific focus areas:
CENTRAL NERVOUS SYSTEM (CNS)
- Technologies, approaches, or platforms that improve delivery of next-generation therapeutics to the brain
- Disease-modifying therapies for defined patient populations with CNS diseases (including neuropsychiatry but excluding neurovascular, neuro-oncology, and psychedelics)
INFLAMMATION AND IMMUNOLOGY
- Novel tolerization strategies for managing immune-driven conditions (e.g. allergy, autoimmune disease, and transplant rejection)
- Novel approaches for targeting memory T cells in immune-driven conditions
METABOLIC DISEASE
- Novel therapeutics or approaches that attenuate inflammation and prevent or reverse resulting tissue fibrosis in metabolic disease.