From Lab to Clinic: JDRF-Funded Researchers Launch Study of New Drug's Ability to Improve Islet Cell Transplants

--First patient treatment begins to test whether the drug emricasan, a pan-caspase inhibitor, could improve and maintain insulin independence in islet cell transplantation patients with type 1 diabetes--

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Tara Wilcox-Ghanoonparvar
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New York, NY, July 26, 2012--After islet cell transplantation, a patient with type 1 diabetes (T1D) often loses insulin independence over time due to the loss of islet cells, which occurs for a number of reasons including cell stress from the transplantation process. To address this major hurdle in the therapy's success, JDRF-funded researchers at the University of Alberta in Canada have begun treatment of the first patient in a pilot clinical trial of the drug emricasan-a pan-caspase inhibitor-to test its ability to improve and maintain islet cell viability and insulin independence rates in people with diabetes who have undergone islet cell transplantation.

"JDRF is excited to have supported positive preclinical research of emricasan for islet cell transplants, and to now fund this important clinical research," said Albert Hwa, Ph.D., JDRF's senior scientific program manager for cure therapies. "As we explore ways to remove obstacles to long-term function of islet cells after transplantation, we come closer to a way to restore and maintain long-term insulin independence in people with type 1 diabetes, thus lifting the burden of constant insulin dependence for people with the disease."

T1D is an autoimmune disease in which the body destroys beta cells in the pancreas that produce insulin, a hormone that converts food into energy. People with the disease are insulin-dependent, and must carefully monitor and manage their blood sugar levels around the clock. Islet cell transplantation is one promising research avenue in which cells from a donor pancreas are transplanted into a person with T1D, restoring blood glucose regulation. However, transplanted islet cells may fail to survive in their new environment, one contributing factor being the activation of caspases-molecules inside cells that mediate cell destruction. The activated caspases can lead to islet cell death during and after cell isolation from the donor pancreas, and also after the transplantation procedure. Their death results in islet cell function that is suboptimal for maintaining insulin independence in the patient.

Emricasan is a novel drug by Conatus Pharmaceuticals Inc., which inhibits activated caspases. A 12-week Phase II study in patients with Hepatitis C virus showed that the oral form of emricasan safely and significantly improved signs of liver damage. This latest trial is the first time the drug is being tested in humans with diabetes in the setting of islet cell transplantation. The trial's primary investigator, A. M. James Shapiro, M.D., Ph.D., and his team at the University of Alberta will conduct two consecutive pilot studies, each with six patients and two different doses of emricasan for 14 days. The patients will be treated with emricasan two hours prior to islet cell transplantation, and then for two weeks following transplantation. Based on data from the current study, optimal dosing will be determined as researchers move to plan a randomized, placebo-controlled study to explore the drug's safety and efficacy in islet cell transplantation.

"Turning off the death signals in islet transplant is going to be game-changing," said Dr. Shapiro. "It opens up the possibility of treating multiple recipients from a single donor, and may facilitate induction of immune tolerance. A start on the first in-human clinical trials, supported through JDRF in partnership with Conatus and the University of Alberta, is an exciting moment. We've been working on this in the lab, building up to the trial for the past six years. Now it's really happening in patients. It's too soon to tell how effective it will be, but that's the purpose of the trial."Dr.

Hwa added: "In addition to its implications for the future of islet cell transplantation, Dr. Shapiro's research may also prove useful for transplanting future alternative islet cell sources, such as cells derived from human embryonic stem cells or from other animal species.


About T1D

In T1D, a person's pancreas stops producing insulin, a hormone that enables people to get energy from food. People with T1D need to test their blood sugar and give themselves insulin (with injections or an insulin pump) multiple times every day, and carefully balance insulin doses with eating and daily activities throughout the day and night. However, insulin is not a cure for diabetes, and even with that intensive care, a significant portion of the day is still spent with either high or low blood sugar, placing people with T1D at risk for devastating complications such as heart attack, stroke, blindness, and amputation.

About JDRF

JDRF is the leading global organization focused on type 1 diabetes (T1D) research. Driven by passionate, grassroots volunteers connected to children, adolescents, and adults with this disease, JDRF is now the largest charitable supporter of T1D research. The goal of JDRF research is to improve the lives of all people affected by T1D by accelerating progress on the most promising opportunities for curing, better treating, and preventing T1D. JDRF collaborates with a wide spectrum of partners who share this goal.Since its founding in 1970.

JDRF has awarded more than $1.6 billion to diabetes research. Past JDRF efforts have helped to significantly advance the care of people with this disease, and have expanded the critical scientific understanding of T1D. JDRF will not rest until T1D is fully conquered.

Lets turn type one into type none