Researchers have discovered that the SDI1 (senescent derivedinhibitor) gene, licensed to Agis Pharmaceuticals Inc., regulatescell proliferation. The finding is reported in two articles intoday's issue of Cell by scientists from Baylor College ofMedicine and Johns Hopkins University.
The researchers describe how SDI1 is controlled by the p53tumor suppresser gene and how p53 functions to stop cellgrowth and tumor formation. "In normal cells, p53 causes highlevels of expression of the SDI1 gene, which binds to andinactivates cyclin dependent kinases (CDKs)" that function toactivate the cell cycle, said Jim Smith, one of the founders ofAgis.
Without CDK function, cells cannot duplicate, Smith added."When p53 is not functional, SDI1 levels drop and CDKsfunction to promote cell duplication. Without regulation, cellgrowth becomes uncontrolled and can lead to tumor formation."
Agis noted that the p53 gene is found in more than 50 percentof the known types of human cancers.
Bert Vogelstein and his colleagues at Johns Hopkins identifiedthe WAF1 gene as an effector of p53, and Wade Harper and hiscolleagues at Baylor identified the CIP1 gene as an inhibitor ofCDKs. Both genes are the same as the SDI1 gene.
A third paper that reports the cloning of the SDI1 gene as aninhibitor of DNA synthesis in Smith's lab will be published inan upcoming issue of Experimental Cell Research.
Jim Smith and Olivia Pereira-Smith, both professors at Baylor,discovered the SDI1 gene in 1991. Baylor filed for a patent forthe SDI1 technology in 1991 and received a notice of allowancein October. Together with Baylor's for-profit subsidiary, BCMTechnologies Inc., the Smiths founded Agis in 1992. Agis has itsoffices at BCM in Houston.
The objective of Agis is to develop therapies to control aberrantcell proliferation through the restoration and use of senescentgene activity for cancer and other hyperproliferative diseases.Jim Smith said Agis will further explore the therapeuticactivity of the SDI1 gene for cancer and other diseases, such aspsoriasis and secondary cataracts, "where the inhibition of cellproliferation is desired."
Smith's lab also has found four pathways that control whethercells go into a normal senescent state (do not divide) or go intoan immortal cancerous state. Each pathway should beassociated with one gene, Agis' director of businessdevelopment, Bethany Pimentel, told BioWorld.
Columbine Venture Funds and Medical Venture Holdings Inc.provided Agis with an initial seed investment of $750,000 inJuly with a commitment for a $2 million follow-on offering tobe completed this winter.
-- Brenda Sandburg News Editor
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