HEM Pharmaceuticals Corp. of Philadelphia announced Mondaythat it has received approval from the FDA to take itsribonucleic acid drug Ampligen into Phase II/III trials forchronic fatigue syndrome (myalgic encephalomyelitis, or ME,syndrome).
Ampligen is the double-stranded synthetic RNA compound PolyI: poly C12U. This RNA therapeutic is believed to act in twoways: by switching on enzymes that are critical to anti-viraldefense mechanisms and by regulating the level of immunesystem modulators.
"One of the earliest responses following virus infection is theactivation of the 2-5A synthetase and the p68 kinasepathways," Nigel Webb, president of privately held HEM toldBioWorld. Both are anti-viral. In normal viral infections, thesynthetase enzyme recognizes the presence of the virus by itslong, double-stranded RNA; the virus triggers a series ofbiochemical reactions that eventually shut down viralproduction by digesting viral messenger RNA. "The p68 kinaseis also activated by double-stranded RNA," Webb explained.
But in chronic viral infections, Webb said, "the virus hasfigured out how to shut down that anti-viral pathway. ... Byadding Ampligen, we are activating the system which the virushas shut down."
The clinical history of double-stranded RNA drugs in humanshasn't been good, however. For instance, DuPont of Wilmington,Del., was testing HEM's Ampligen on HIV patients in the late1980s and found it to be "ineffective." And "the poly I: poly Ctested by Merck was highly toxic," Webb said. But HEM hasfound a particular configuration of the synthetic RNA moleculethat "substantially reduces the product's toxicity," Webb toldBioWorld.
Ampligen currently is in early clinical trials for a variety ofindications, both anti-viral (AIDS, hepatitis B, and herpes virus6, which is at least associated with ME syndrome), and cancer(renal cell carcinoma, melanoma and lung cancer). Ampligenhas orphan drug status for AIDS and metastatic renal cellcarcinoma. -- Jennifer Van Brunt
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