Ariad preclinical data

ARIA published animal results, first presented at a gene therapy meeting in May, demonstrating that a dimerizing drug can bring together two parts of a gene promoter to activate production of a therapeutic protein. As reported in Nature Medicine, nude mice were implanted with human cells expressing both human growth hormone and genes that produce two fragments of different gene activation proteins (transcription factors). The two transcription factor fragments each have high affinity for the oral drug rapamycin.

The mice then were given an analog of rapamycin, without the drug's immunosuppressant properties. The rapamycin brought together the fragments, which in turn activated the target gene (hGH). Secretion of hGH was dependent on the dose of rapamycin. Elevated levels of growth hormone lasted for more than a day, whereas injected hormone persists for only a few minutes.The first clinical tests of the company's dimerizing drugs are planned for 1997. ARIA said the technique can be used with all of the gene delivery systems in development, including viral and nonviral fectors, direct DNA injection, and in vivo or ex vivo delivery. ...