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Apr 26, 2013

Hormone Holds Promise for Replacing Insulin Injections

  • Evotec said today that its CureBeta collaboration with Harvard University and Johnson & Johnson’s Janssen Pharmaceuticals subsidiary has discovered a new hormone that holds promise as a treatment for diabetes, based on its action in a mouse model.

    The hormone, called betatrophin, controlled the proliferation of the pancreatic beta cells that produced insulin in the mouse model, thus serving as a key mechanism that controls beta cell mass, according to a research team led by CureBeta’s key collaborator Douglas A. Melton, Ph.D., and his postdoc Peng Yi. Dr. Melton is co-director of the Harvard Stem Cell Institute and Thomas Dudley Cabot professor in the natural sciences at Harvard’s Department of Stem Cell and Regenerative Biology.

    The model induced dramatic pancreatic beta cell proliferation—at up to 30 times the normal rate—and beta cell mass expansion that researchers connected to betatrophin, a secreted protein primarily expressed in liver and fat. That expression correlated with beta cell proliferation in other mouse models of insulin resistance, as well as during gestation.

    Specifically, transient expression of betatrophin in the liver of a mouse significantly and specifically promoted pancreatic beta cell proliferation, expanded beta cell mass, and improved glucose tolerance.

    “Thus, betatrophin treatment could augment or replace insulin injections by increasing the number of endogenous insulin-producing cells in diabetics,” the research team concluded in its study, published online yesterday in Cell. The study will appear in the journal's print edition May 9.

    In a statement for Harvard, Dr. Melton envisioned a dramatic change in how often people with diabetes would need to inject themselves with insulin: “If this could be used in people, it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year.”

    Before that can happen, however, betatrophin will require testing in humans, whose plasma has been found to have the hormone. Dr. Melton envisions betatrophin in human clinical trials within three to five years.

    Evotec said all intellectual property associated with the findings have been licensed to the company since March 2011, then sublicensed to Janssen in July 2012, when it joined the CureBeta collaboration. As a result, Janssen received exclusive access to a series of drug candidates designed to trigger the regeneration of insulin-producing beta cells.

    “Restoring beta cell mass and function is the most promising approach to slow down or reverse disease progression in diabetic patients,” Cord Dohrmann, Ph.D., Evotec’s CSO, said in a statement.

    CureBeta was established in 2011 by Evotec, Harvard, and the Howard Hughes Medical Institute—where Dr. Melton has been an investigator since 1994—with the goal of pursuing identification and development of physiological mechanisms and targets that regulate beta cell replication.

    Dr. Melton’s research began by focusing on type 1 diabetes, following the diagnosis of his son with the disease; his daughter was later diagnosed with it, too. “We were just wondering what happens when an animal doesn’t have enough insulin. We were lucky to find this new gene that had largely gone unnoticed before,” he told Harvard.

    “I would like to tell you this discovery came from deep thinking and we knew we would find this, but it was more a bit of luck,” he added.

    Evotec has 15 scientists working to develop betatrophin. Originally a drug developer, Evotec has shifted its focus in recent years toward forming drug discovery alliance and development partnerships with top-tier pharmaceutical and biotechnology companies in key therapeutic areas that include neuroscience, pain, metabolic diseases, oncology, and inflammation.

    In addition to CureBeta, Evotec has long-term discovery alliances with partners that include Bayer, Boehringer Ingelheim, CHDI, Genentech, MedImmune/AstraZeneca, and Ono Pharmaceutical. On Monday, Evotec said it was extending by three additional years its alliance with Roche’s Genentech subsidiary, formed in May 2010.


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