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Neurocrine Biosciences Inc. Message Board

  • noitalll noitalll Feb 16, 1998 5:13 PM Flag

    New development - anyone care to comment

    Neurocrine Biosciences Discovers New Small Molecule Growth Factor Technology

    SAN DIEGO, Feb. 16 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced the discovery of a novel
    strategy which permits the development of small molecule potential therapeutic agents that increase endogenous insulin-like growth
    factor (IGF) to treat diseases and disorders of the central and peripheral nervous systems as well as the endocrine system. In a
    paper published in the February 17th issue of "Proceedings of the National Academy of Sciences," scientists from Neurocrine
    demonstrated that displacement of IGF from their binding proteins is neuroprotective in a clinically relevant model of stroke and may
    have broader applications for the treatment of other neurodegenerative disorders as well as brain trauma and spinal cord injury.

    Insulin-like growth factors (IGF-I and IGF-II) are peptides essential for normal growth and development. Their actions are
    mediated by Type I and Type II IGF receptors and are modulated by a family of six binding proteins, which inactivate the growth
    factors. Brain injury is commonly associated with increases in IGF and their insulin-like growth factor binding proteins (IGF- BPs).
    The authors reported that displacement of endogenous IGF from the binding proteins using a selective IGF-BP inhibitor would
    increase the level of free IGFs. The elevated free IGF levels can then produce neuroprotective effects comparable to those seen with
    administration of IGF-I. In this study IGF-BP inhibitors gave the same level of protection as IGF-I itself. In addition, both IGF-I and
    IGF-BP inhibitors showed substantial protection in the middle cerebral artery occlusion (MCAO) model even when administration was
    delayed for 1 hour after occlusion, similar to the clinical setting. These results have subsequently been reproduced by Neurocrine
    scientists using small organic "drug like" molecules which elevate endogenons IGFs by inhibiting the binding of this growth factor to
    IGF binding proteins.

    In addition, IGF-BP inhibitors modulate the body's own IGF, which may have an improved safety profile over current methods which flood the system with the administration of large amounts of IGF-I. By specifically targeting one of the six IGF-BPs, local increases in IGF may be achieved to provide a regional therapeutic effect and potentially reduce side effects, which may result from body-wide increases in IGF.

    "The advantage of this approach is that small molecules have the ability to cross the blood-brain barrier, which is
    essential in the treatment of central nervous system diseases such as stroke. In addition, therapeutic agents can be designed to be
    active via oral or intravenous (I.V.) administration to treat chronic and acute indications such as stroke, head trauma,
    Alzheimer's disease, Parkinson's disease, multiple sclerosis, diabetes and Peripheral neuropathies," said Errol B. De Souza, Ph.D
    Executive Vice President of Research and Development of Neurocrine Biosciences.

    "Neurocrine has identified small molecule leads and is currently optimizing those leads into drug candidates," added De Souza.

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