Nisanne Ghonem, PharmD, PhD
2017 Advance-CTR Mentored Research Award Scholar
URI College of Pharmacy
Congratulations to Advance-CTR awardee Nisanne Ghonem, PharmD, PhD who recently received funding from United Therapeutics to move her research from the bench to the bedside.
Dr. Ghonem is a 2017 recipient of Advance-CTR’s Mentored Research Awards, in which she investigated the efficacy of treprostinil, a prostacyclin analog, in reducing kidney ischemia-reperfusion injury in rats. Dr. Ghonem is now moving forward with a pilot clinical study to investigate the efficacy of treprostinil in adult kidney transplantation. Learn more about her research and what’s next.
“A Phase I/II Study Evaluating the Preliminary Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During De Novo Adult Kidney Transplantation” (United Therapeutics)
Approximately 2 million people worldwide and more than 650,000 Americans are affected by end-stage kidney diseases (ESRD). Kidney transplantation (KTx) is the standard care for patients with ESRD. However, donor shortage is a major factor limiting the organs available for transplantation. This shortage has forced centers, including Rhode Island Hospital, to expand their criteria and accept donors from extended criteria or marginal donors. Extended criteria donor organs are most susceptible to ischemia-reperfusion (I/R) injury and a 30-70% risk of delayed graft function (DGF), carrying high mortality if patients are not re-transplanted immediately, further depleting the donor pool.
The pathophysiology of kidney I/R injury includes direct cellular damage due to the ischemic insult as well as delayed graft injury post-reperfusion, resulting in varying degrees of graft dysfunction and graft failure. I/R injury includes inflammatory response, where substances such as pro-inflammatory cytokines are locally released to promote vasoconstriction, platelet aggregation and leukocyte adherence, contributing to graft damage. Currently, no treatment for I/R injury during KTx is available. Novel therapeutic strategies are urgently needed to address these unmet needs of KTx.
Through my Mentored Research Award, I examined whether treprostinil, a prostacyclin analog, would improve blood flow to the kidney, inhibit inflammation and vasoconstriction, thereby reduce kidney I/R injury using a rat model of bilateral kidney I/R injury. The preliminary results provided the proof-of-concept data necessary for a clinical investigation and have been published in Nephrology, Dialysis, and Transplantation.
Based on these positive results, I was able to secure funding from United Therapeutics to move forward with a pilot clinical study to test the safety and efficacy of treprostinil in reducing ischemia-reperfusion injury during adult kidney transplantation.
I continue to work with my mentor on the Advance-CTR award, Fatemeh Akhlaghi, PharmD, PhD, and my collaborator Reginald Gohh, MD on the study, which will be carried out at Rhode Island Hospital; patient enrollment is anticipated to start in Spring 2020.
“Dr. Ghonem has built a productive laboratory which would further facilitate submission of extramural grants. The provision of this funding has generated a truly viable translational investigation that may transpire to a new therapy in kidney transplant recipients,” said Dr. Akhlaghi of her mentee.
The proof-of-concept findings from this project will support future collaborative research to investigate the pharmacological, metabolic, and clinical aspects of treprostinil for the treatment of kidney diseases.
The FDA recently published reports emphasizing the urgent need for therapies to reduce delayed graft failure during adult kidney transplant. Ultimately, this research may offer an innovative strategy to reduce I/R injury and reduce delayed graft function for kidney transplant recipients.
The success of my Mentored Research Award project, coupled with the potential outcomes of the clinical research, may provide a pharmacological treatment to improve outcomes and graft survival for patients undergoing kidney transplantation. These would include improved kidney graft function, minimized post-transplant complications, and potentially increase the number of marginal organs available for transplantation, which would otherwise be discarded.
This award has given me the opportunity to meet and collaborate with RI clinicians who are interested in translating the animal findings into clinical studies, and researchers who may serve as future collaborators. The proof-of-concept findings from this project will support future collaborative research to investigate the pharmacological, metabolic, and clinical aspects of treprostinil for the treatment of kidney diseases.
The funding and support I received as a junior faculty through Advance-CTR, both professional and scientific, has not only jump-started my research program, but it also turned my hopes of translating animal study findings to the clinic into a reality – which may ultimately improve patient lives.