Signal Pharmaceuticals Inc., whose drug discovery efforts targetregulation of gene expression, signed a three-year agreement withRoche Bioscience, to find small-molecule compounds to treat painand lower urinary tract disorders.

In the collaboration, San Diego-based Signal will develop peripheralneuronal cell lines for use by Roche Bioscience, of Palo Alto, Calif.,in screening drugs against specific genetic targets. Roche Bioscienceis a research division of Roche Holding Ltd., of Basel, Switzerland.

Signal's president and CEO, Alan Lewis, said his company willdevelop cell lines for Roche based on Signal's technology forgenerating central nervous system neuronal cell lines to test drugs.Peripheral neurons are those outside the brain.

The collaboration with Roche focuses only on pain and lower urinarytract disorders. Signal will retain rights to the peripheral neuronal celllines for use in other disease areas. The company is using its humanbrain cell lines to study genetic targets involved in psychiatric andneurodegenerative disorders, such as Alzheimer's disease.

Neuroscience research typically employs non-human neuronal cellsor neuronal receptors cloned into other types of cells to test drugactivity.

Screening small-molecule compounds against genetic targets inhuman neuronal cells, Lewis observed, enables researchers to studythe effect of therapeutic candidates within "the milieu of the wholeneuron. You have access to the whole signaling cascade associatedwith neurons."

Signal's drug discovery programs focus on intracellular signalingenzymes that activate transcription factors, which in turn trigger geneexpression. One goal is to find small-molecule compounds that blocksignals and shutdown genes before they have a chance to producedisease-causing proteins.

Signal, Lewis said, "is one of the few small firms to have a strongproprietary position" in technology for creating human neuronal celllines. A key challenge in the process is growing stable cells for use inresearch.

Signal takes human fetal brain cells and uses growth factors "toperpetualize the cells and immortalize the cells for use in assays,"Lewis said. "We also can differentiate cells such as making neuronallines, astrocytes and glial cells."

The deal with Roche is the third major alliance forged by Signal inthe last six months.

The company signed drug discovery alliances with Tanabe SeiyakuCo. Ltd., of Osaka, Japan, in April 1996 for osteoporosis andinflammatory diseases and Akzo Nobel Pharma Group, of Arnhem,the Netherlands, in August 1996 for gynecological, cardiovascularand neurological diseases.

The three-year collaborations with Akzo's subsidiary N.V. Organon,of Oss, the Netherlands, and with Roche are more narrowly focusedthan the four-year Tanabe alliance, which could be worth up to $46million to privately held Signal.

Financial terms of the Roche and Akzo agreements were notdisclosed. In both deals, the collaborators agreed to pay Signal up-front license fees, fund research, make milestone payments andcontribute royalties on marketed products in exchange for exclusiverights to compounds emanating from the alliances. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.

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