Ariad Gene Therapeutics Inc., a subsidiary of AriadPharmaceuticals Inc., has licensed gene therapy technologyfrom Harvard and Stanford universities that uses molecules toactivate signaling pathways in cells to produce therapeuticproteins.

Ariad of Cambridge, Mass., announced last week that itobtained sole rights to the technology, which it is developing inassociation with Stuart Schreiber of Harvard and GeraldCrabtree of Stanford, who with their colleagues designed thetechnology. Their research was published in the Nov. 12, 1993,issue of Science.

Ariad explained that the gene therapy technology "is based onthe principle that the activation of cell-signaling pathwaysdepends on the clustering in groups of two or more of proteinswithin the cell. This activation leads to transcription of specificgenes and the production of new cellular proteins."

Ariad's founder, chairman and chief executive officer, HarveyBerger, explained that a gene cassette -- consisting of a cellularreceptor, the gene for the therapeutic protein of interest and achimeric protein necessary to induce apoptosis -- is insertedinto target cells. Three orally active drugs are thenadministered to control the expression of the proteins by theengineered cells.

Drug I is a molecule related to FK1012, a derivative of theimmunosuppressive drug FK506, that brings together thegenetically engineered cellular receptors within the cell. Theclustering activates the signaling pathway and induces theproduction of therapeutic proteins, such as hormones, enzymes,lipid receptors or neurotransmitters.

Berger said Drug II, a derivative of FK506, pushes the receptorsapart, thereby deactivating the signaling pathway and shuttingdown production of the therapeutic protein. Drug III, which isrelated to FK1012, clusters an engineered "self-elimination"receptor (an element of the gene cassette) and inducesapoptosis, or programmed cell death, thus eliminating theengineered cells if they are no longer needed or causeundesirable side effects.

Drugs I and II work on the same receptor, while Drug IIIworks on another receptor engineered into the cell.

None of the three drugs have immunosuppressive activities.Berger said the first two drugs can be given sequentially forcyclical drug delivery.

Ariad Pharmaceuticals Inc. formed Ariad Gene Therapeutics asa subsidiary last month to develop the gene therapytechnology.

Ariad began animal testing with the molecules during thefourth quarter of last year. Berger said that this technology fitsin with what the company has been working on: developmentof small molecules that can affect intracellular signaltransduction pathways and protein trafficking.

According to Ariad, the gene therapy technology could be usedto engineer cells expressing hormones or cytokines, such aserythropoietin or granulocyte-macrophage colony-stimulatingfactor (GM-CSF). "Patients may be able to take a pill whichregulates their own production of these hormones instead ofbeing treated chronically with the hormone or cytokine in thehospital or doctor's office," Ariad said.

In addition, the company said the technology could haveapplications in the development of transgenic animals andcould form the basis for a new generation of pharmaceuticalsthat manipulate the biological response for specific therapeuticeffect.

-- Brenda Sandburg News Editor

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