Brain Projects to Reap Dividends for Neurotech Firms

by James Cavuoto, editor

In much the same way that the biotechnology and pharmaceutical industries have benefited from the ambitious efforts to map the human genome, work underway at several private corporations and research institutions to map the functional connections of the human nervous system may well prove fruitful for the neurotechnology industry. While our understanding of biological processes active at the molecular and subcellular levels have advanced profoundly over the last two decades, progress at deciphering exactly how the central nervous system effects specific sensory, motor, and cognitive functions has been much more restrained.

This shortcoming in scientific understanding has hampered much of the effort to build useful neural prostheses and stimulation devices. For example, manufacturers of deep-brain stimulation systems have spent years exploring precise regions of the subthalamic nucleus to stimulate for most effective treatment of Parkinson’s disease and essential tremors. Researchers working on motor prostheses have been hampered by their inability to trace neural connections from motor cortex to spinal cord, to specific muscle fibers. And development teams working on visual prosthesis projects would benefit greatly from a better understanding of the precise neural pathways involved with visual perception and scene analysis. Manufacturers of neurodiagnostic systems would also benefit greatly from an enhanced store of knowledge about brain activity corresponding to specific neurological and psychological disorders. Further, just identifying connections presents an incomplete view of nervous system functions, as connections can be excitatory, inhibitory, state-dependent, and change their magnitude over time.

One of the first efforts at cataloging the functional connections within the brain was the Project Brain initiative at the University of Southern California, headed by Michael Arbib with funding from the National Institutes of Mental Health. The project endeavored to create a collection of distributed neuroscience databases to which multiple researchers could contribute data at the molecular, subcellular, cellular , network, or systems level.

In 1999, NIMH issued four neuroinformatics program announcements for its Human Brain Project with the goal of bringing together neuroscientists, computer scientists, engineers and mathematicians working on models of the human brain. Among the institutions that secured funding is Caltech, for a neuronal database derived from its Genesis simulator. The Caltech team, headed by James Bower, has built a set of software tools written in Java called Modelers Workbench, which allows users on the Internet to search for and visualize different nervous system components.

Another modeling database, ModelDB, is maintained by the developers of the neural simulation package NEURON (Michael Hines and Ted Carnevale at Yale and John W. Moore at Duke), and is designed to enable scientists to contribute data and models, and simplify implementation of models by users.
George Mason University also received funding for its software package L-Neuron, which compiles topographical and morphological information about dendritic branches in an effort to construct virtual neurons that are anatomically indistinguishable from actual neurons. In still another NIMH-funded project, Anders Dale at Massachusetts General Hospital is building a two-dimensional map of the human cerebral cortex in an effort to develop a surface-based coordinate system.

On the commercial side, Neurome, Inc. of La Jolla, CA is developing a series of quantitative databases of nervous system attributes at the molecular, gene, cellular, and circuit level. The company, founded in 2000 by Scripps Research Institute scientists Floyd Bloom and Warren Young, along with John Morrison from Mount Sinai School of Medicine, has as clients several pharmaceutical and biotechnology companies looking to discover gene targets useful in treating brain-based diseases. The founders received $9 million in funding from a team of private biotech investors including Digital Gene Technologies and Elan Pharmaceuticals. Scripps and Mount Sinai also received shares in the venture.

Neurome management is pursuing an ambitious goal: “Nothing less than a complete understanding of the role and function of each structure of the human brain—from cognition to appetite, from learning to motor function, from memory to sleep.” Neurome has developed a suite of technology tools to help them collect data on the architecture and functions of brain structures. These include NeuroZoom, a computer-aided extraction, imaging, and analysis tool; BrainArchive, an electronic brain atlas of structure and circuitry data, and MiceSlice, a standardized method of preparing brain sections.

Another technology firm constructing models of the nervous system is Physiome Sciences of Princeton, NJ. The company has developed a series of biological modeling tools, including an “In-Silico Cell” software architecture that helps researchers visualize and simulate signaling networks such as ion channels in a neuronal cell. Physiome has entered into an alliance with IBM in which Physiome will use the computer firm’s supercomputing technology and IBM will license Physiome’s biological modeling technology.

While there is a great deal of current interest in genomic and proteomic approaches to cataloging nervous system function, both pharmaceutical and device companies in the neuro space are dependent on efforts to understand the nervous system at higher levels of organization. This is particularly the case for neurological diseases and disorders such as stroke or spinal cord injury that cannot readily be cured with the discovery of a single drug, gene target, or protein. Treatment of more complex neurological and psychiatric disorders will undoubtedly require a rich store of knowledge of which nervous system components are involved with specific functions or dysfunctions, whether the ultimate treatment is with drugs, cell therapies, or neurotechnology devices. While the current efforts at mapping the human “neurome” may not have attracted as much attention as the human genome project, the implications could very well be just as great.



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