Lexicon Genetics Discovers Drug Target for Potential Treatment of Depression; Gene Knockout Increases Activity and Mobility
THE WOODLANDS, Texas, Jan. 7 /PRNewswire/ -- Lexicon Genetics Incorporated (Nasdaq: LEXG - news) today announced that the Company has discovered and validated in vivo a new drug target, named LG527, to develop potential treatments for depression. Lexicon scientists discovered the human gene encoding the new target using Lexicon's gene trap technology. The Company found that mice lacking the enzyme LG527 showed a dramatic increase in activity levels and mobility. This type of response indicates a potential role for the new enzyme in the treatment of depression because typical symptoms of the disease include decreased energy, activity and mobility. Scientists at Lexicon are currently working to discover a drug that inhibits the LG527 enzyme, which could lead to new therapy for depression.
``We are very pleased to announce this latest target from our drug discovery pipeline and to further substantiate the critical mass of in vivo validated targets that we are advancing into our pharmaceutical division for drug screening,'' said Arthur T. Sands, M.D., Ph.D., President and Chief Executive Officer of Lexicon. ``This discovery demonstrates the power of our gene knockout technology to determine how genes function to control the physiology of the mammalian brain. Our pipeline of targets in cardiology, immunology, neurology, oncology, and metabolism demonstrates the broad applicability of our gene knockout technology for the discovery of new therapeutics.''
Bioinformatics computer analysis of the DNA sequence of LG527 indicates the novel gene is related to enzymes that are known to regulate behavior. The significance of the enzyme in the brain was corroborated by gene expression studies that showed exclusive expression of the gene in the central nervous system. Lexicon scientists believe that LG527 may represent a novel pathway for regulation of neurotransmission in the brain.
The function of the target was uncovered via the Company's industrialized gene knockout program in which mice lacking specific genes are studied to uncover favorable medical profiles for developing new drugs. In an open field study, ``knockout'' mice missing the LG527 gene traveled distances more than four times that of control mice, suggesting the knockout mice were hyperactive. In a related study, the mice showed a significant increase in mobility when compared to the normal controls. Lexicon uses a comprehensive battery of advanced medical tests to discover the physiological activity of proteins encoded in the mammalian genome and their potential medical applications. LG527 is the third major target from Lexicon's drug discovery program to be publicly disclosed. The Company recently announced targets that are rapidly being moved into drug screening in the fields of cardiology and immunology.
``Our battery of physiological and behavioral testing provides compelling functional information about LG527 and gives us an initial understanding of how a drug targeting this enzyme might be used to treat depression,'' said Thomas Lanthorn, Ph.D., Lexicon's Director of Neurology. ``The discovery of LG527 is a result of Lexicon's genomics discovery program combined with systematic behavioral and neurological testing to pinpoint new targets for therapies for serious neuropsychiatric disorders.''
In the year 2000, antidepressants were the third-largest therapy class, accounting for $13.4 billion in sales (IMS Health). Depression affects more than 19 million American adults, making it the most common serious neuropsychiatric disease in the United States (NIMH). CNS disorders encompass a broad array of disease areas, including Alzheimer's disease, Attention Deficit Hyperactivity Disorder (ADHD), depression and Parkinson's disease. The treatments that are currently available for these diseases are among the most frequently prescribed drugs in the United States, yet often have limited efficacy or significant side effects for many patients. |
