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New Therapeutic Uses 2015 Project Awards

In July 2015, NCATS announced nearly $3 million to fund cooperative agreements with four academic research groups to conduct pre-clinical validation studies, clinical feasibility studies or proof-of-concept clinical trials to test whether the selected assets may be effective against a previously unexplored disease target. Four disease areas are represented:

  • Type 2 diabetes
  • Acute myeloid leukemia (an aggressive blood cancer)
  • Glioblastoma (one of the most aggressive brain tumors in adults)
  • Chagas disease (a neglected tropical disease causing heart, digestive and neurological problems)

Industry partner companies are providing the drug and matched placebo as well as data and other resources at no cost to NCATS or the academic institutions. These projects are in response to PAR-14-210, PAR-14-211 and PAR-14-212:


Anti-inflammatory Small Drug as Adjunctive Therapy to Improve Glucometabolic Variables in Obese, Insulin-Resistant Type 2 Diabetic Patients

Academic Partner: Nick Giannoukakis, Ph.D., Allegheny Health Network Research Institute, Pittsburgh
Industry Partner: AstraZeneca
Grant Number: 1-UH3-TR001372-01

More than 29 million Americans have type 2 diabetes (T2D), a debilitating disorder and the seventh leading cause of death. The main risk factor for T2D is obesity, which leads to chronic inflammation that can disrupt the body’s sensitivity to insulin, a hormone associated with T2D that controls blood sugar levels. T2D inflammation also is linked to higher risk for cardiovascular disease. The body’s white blood cells, which are involved in the body’s immune response, may underlie T2D inflammation. This research team will test a leukocyte-selective anti-inflammatory compound as an add-on medication for obese, insulin-resistant T2D patients. The investigators will measure its ability to improve T2D and reduce inflammation. This work may lead to an improved T2D therapy that could enable better outcomes and reduces risk for other diseases. The compound also may be useful for treating other inflammation-associated disorders.

Watch Giannoukakis discuss this research:

Right-click to download a transcript (2KB). The media player works best when viewed in Chrome or Internet Explorer browsers.

Evaluation of AZD9291 in Glioblastoma Patients with Activated EGFR

Academic Partners: Madan M.Kwatra, Ph.D., and Glenn J. Lesser, M.D., Duke University, Durham, North Carolina
Industry Partner: AstraZeneca
Grant Number: 1-UH2-TR001370-01

Glioblastoma (GBM) is one of the most aggressive and common brain tumors in adults. Current treatments have failed to extend median survival time beyond 15 months, indicating an urgent need for a more effective GBM therapy. To achieve this goal, scientists must better understand the molecular machinery that drives GBM. Recent work indicates that a subset of GBM tumors show elevated activity of a protein known to affect tumor growth called epidermal growth factor receptor (EGFR). Tumors with overactive EGFR also have enhanced activity of another protein called HER2. AZD9291 — a compound that can cross the blood-brain barrier and was originally designed to treat lung cancer — blocks the activity of both EGFR and HER2. The proposed studies are designed to find an effective therapy for glioblastoma patients with an activated form of EGFR. This work could lead to the development of a new, more effective and more precise treatment strategy for a specific group of GBM patients.

Four brain scans, one showing normal activity and three showing cases of glioblastoma

This image shows a series of four magnetic resonance imaging (MRI) scans of the brain. On the far left is a normal brain. In the middle on left and right are glioblastoma tumors in the brain’s frontal and occipital lobes, respectively; the scans show significant swelling of the surrounding tissue. On the far right is a glioblastoma tumor in the occipital lobe of a child’s brain. (Wake Forest School of Medicine Photo)

Evaluation of a Cathepsin S Inhibitor as a Potential Drug for Chagas Disease

Academic Partner: James H.McKerrow, M.D., Ph.D., University of California, San Diego
Industry Partner: Sanofi
Grant Number: 1-UH2-TR001369-01

Chagas disease is a neglected tropical disease that currently affects an estimated 7 million people, according to the World Health Organization. Chagas disease is responsible for more than 10,000 deaths worldwide each year, making it the leading cause of heart failure in Latin America and an emerging infection in the U.S. The disease is caused when an insect transmits the Trypanosoma cruzi (T. cruzi) parasite to a person through blood, causing heart, digestive and neurological problems. There are no therapies for Chagas disease approved by the Food and Drug Administration (FDA). The current treatments cause negative side effects and are largely ineffective at later stages of the disease, demonstrating a need for an improved therapy that targets T. cruzi. Scientists have shown that a compound that blocks a critical parasitic enzyme can cure Chagas disease and prevent heart problems in infected animals. Unfortunately, this compound has additional unwanted effects. A drug that works using a similar mechanism but lacks these unwanted effects — called SAR114137 — was originally designed to treat chronic pain and may be a good therapeutic candidate for Chagas disease. These investigators will confirm the drug’s antiparasitic activity in cell culture studies and in infected animals, then test its safety and effectiveness in humans with the disease. This work could lead to a more effective treatment for a neglected and deadly tropical disease.

Wee1 and HDAC Inhibition in Relapsed/Refractory AML

Academic Partner: Steven Grant, M.D., Massey Cancer Center, Virginia Commonwealth University, Richmond
Industry Partner: AstraZeneca
Grant Number: 1-UH2-TR001373-01

Despite advances in understanding the molecular basis of acute myelogenous leukemia (AML), an aggressive blood cancer, patient outcomes often are grim, particularly for individuals with certain mutations or with recurrent or treatment-resistant disease. Although no current therapy exists, scientists have found that a protein called Wee1 represents a potential therapeutic target in AML. AZD1775 is an oral drug that inhibits Wee1, but until now, clinicians have used it primarily for treating other forms of cancer, particularly solid tumors, and generally in combination with standard chemotherapy. Another drug class, histone deacetylase inhibitors (HDACis), recently received orphan drug status from the FDA for the treatment of AML. The investigators found that AZD1775 and HDACis work together to kill human leukemia cells and that the drug combination also improves survival in mice with AML. For this project, the team will continue to investigate the molecular basis of the drugs’ actions in mice and test its safety and effectiveness in patients with recurrent or treatment-resistant AML. These efforts may lead to a new and potentially more effective treatment strategy for patients with this deadly cancer.

Steven Grant, M.D., in the laboratory

Steven Grant, M.D., from the Massey Cancer Center at Virginia Commonwealth University (VCU), investigates novel combination of drugs that cooperate to kill leukemia cells. (VCU Massey Cancer Center Photo)

Last updated: 05-31-2017
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