More than half the genes of the human genome have roles in the unique functions performed by the brain and central nervous system. With the Human Genome Project nominally complete and companion projects close to providing the encyclopaedia of genes for other mammals, the race now begins to determine the function of genes involved in brain function and develop strategies for using this knowledge to treat neurological diseases. Neurogenomics is the new field of elucidating genomic function in the brain.
"The neurosciences have remained a leading growth area of biomedical research for more than 30 years, attracting scientists to the greatest challenge in biology, the understanding of the functions, capacities and diseases of the brain," according to Warren G. Young director of neuropharmacology computing at The Scripps Research Institute in La Jolla, California. His Scripps colleague Floyd E. Bloom, chairman of the department of neuropharmacology agrees noting, "Neuroscience offers the greatest challenge in biology, the leading growth area for biomedical research, and the focus of hope for understanding and treatment of brain-based behaviours and pathologies, from deficits in memory and learning to diseases like Alzheimer's and schizophrenia."
A number of new start-up companies have entered this race. For example, Neurome Inc. is a newly established neuroscience company that will use proprietary technologies to develop standardised, quantitative databases that accurately depict and integrate gene expression patterns in the 3-dimensional context of the brain's structures, circuits and cells. These databases will be used in primary research directed toward the discovery and development of gene targets for enhancement of brain function and treatment of brain-based disease. Neurome's founders are Floyd Bloom, Warren Young and John H. Morrison, Johnson Professor of Geriatrics and Adult Development at the Mount Sinai School of Medicine in New York City, where he is also director of the Kastor Neurobiology of Aging Laboratories and director of the Fishberg Research Center for Neurobiology. The Scripps Research Institute and Mount Sinai School of Medicine are founding shareholders of Neurome.
"With recent advances in genomics and computer science, the demand for procedures that can rapidly extract accurate, reliable quantitative data on brain structure has increased dramatically …" said Young. To meet this demand, Neurome's founders have jointly developed technologies that will permit generation, collection and integration of accurate, three-dimensional volumetric data on gene expression within the brain and correlation of that data with the developing knowledge of the architecture and functions of brain structure, circuits and cells. These technologies include methods for standardised preparation of brain section tissues, for precise, computer-aided extraction, analyses and display of quantitative data from microscope brain images, methodology for archiving, integration and comparison of brain structure and circuitry data and techniques for automated comparison of quantitative, spatial and volumetric data from mice. Neurome's initial mission is to complete commercial development of these technologies and integrate them into a unitary process for production of standardised, quantitative data for use by its own researchers and the company's pharmaceutical, biotech and academic research partners.
On October 20, Neurome announced it had raised $9 million in initial financing from Digital Gene Technologies, Elan Corporation and various private investors. On the same day, Neurome announced a research partnership with Elan Corporation's pharmaceutical subsidiary to study neurodegenerative disorders. "Exploration of gene expression patterns in the mouse brain as they relate to cellular specialisation and circuit characteristics is important to a better understanding of molecular and cellular pathogenesis of Alzheimer's Disease and other neurodegenerative disorders,'' commented Ivan Lieberburg, chief scientific and medical officer of Elan.
The research partnership with Elan has an initial term of three years and may generate up to $4 million in service revenue for Neurome, together with shared ownership of the diagnostic and therapeutic applications of the genes, pathways and mechanisms identified in the research. The partnership will use Neurome's technologies to analyse Elan's proprietary mouse model of amyloid deposition to identify and exploit molecules and pathways relevant to diagnosis and treatment of Alzheimer's Disease.
Another new firm, Neurocrine Biosciences, is a neuroscience-based R&D biopharmaceutical company focused on the development of therapeutic products in the areas of anxiety, depression, insomnia, malignant brain tumours, diabetes and multiple sclerosis. On October 4, Neurocrine filed a registration statement with the Securities and Exchange Commission relating to the proposed offering of three million shares of its Common Stock. Neurocrine also is developing corticotropin-releasing factor 1 (CRF1) antagonists in a research partnership with Janssen Pharmaceutica. A recently completed Phase IIa clinical is the first human clinical study in human patients exhibiting major depression using a CRF1 receptor antagonist. "These findings provide strong evidence for the hypothesis that CRF1 receptor antagonists will have therapeutic potential in the treatment of neuropsychiatric disorders such as anxiety and depression," reports Florian Holsboer of Max Planck Institute of Psychiatry (Munich) who directed the trial (
Another new firm is Cogent Neuroscience in Durham, North Carolina. Max Wallace, co-founder, president and CEO, says the new firm is primarily "an information company." Cogent was co-founded in 1998 with Duke scientists Don Lo and Larry Katz. The firm received $15 million in venture funding in April this year and has added 30 employees since then.
Cogent Neuroscience is using its Gene Rover™ technology platform to screen the human genome for functional gene targets that will serve as the basis for the discovery of new therapeutics. Targets for these new drugs include stroke, brain injury, and neurodegenerative diseases like Alzheimer's Disease, amyotrophic lateral sclerosis (ALS, commonly referred to in the US as Lou Gehrig's disease) and Parkinson's Disease. These and other disorders of the brain involve the degeneration and death of brain cells, leading to loss of memory, loss of cognitive and motor function, and often death. The key gene targets for these diseases are genes that prevent neuronal cell death, that promote the regrowth and renewal of brain circuits and brain tissue, and that are expressed in the relevant parts of the brain.
Cogent has improved existing methods of gene discovery and developed a way to shoot DNA-coated gold particles into slices of live rat brain tissue. After embedding the gene in the brain tissue, they cause stroke-like damage. Examined under a microscope, the brain tissue reveals whether the embedded genes protected it from the damage. The company has industrialised this procedure and can process and examine 4,000 slices a day. Cogent has filed for patents on 42 genes that show protective effects.
Previously, using live, intact brain tissue was impossible, so Cogent's proprietary methods may have given it a lead in the hunt for helpful brain genes. Using this technology, Cogent is first to identify the function of genes that could be key to the diagnosis and treatment of stroke, Alzheimer's and other major neurological diseases. Rather than developing disease treatments that face ten years of multiple US Food and Drug Administration clinical trials, Wallace decided Cogent should first develop information it can sell to large pharmaceutical and biotech companies. "We feel we've achieved critical mass now, a point on the value curve where you can market what you have."