Craig Dionne has a record of experience in drug development and a lot of friends in the pharmaceutical industry. But when his friends first heard about the experimental drug he started working on some years ago, he says their initial reaction was alarm—to put it mildly.
“They told me I was a fool,” Dionne says affably. Dionne is CEO of San Antonio, TX-based GenSpera, which has now started a second round of early stage clinical trials on the experimental drug he took a chance on. He’s hoping the trials are about to show his friends he was right.
Back in the early 1990s, Dionne and his collaborators at Johns Hopkins University saw potential for a cancer drug in a highly potent toxin, thapsigargin, found in a common Mediterranean weed called Thapsia Garganica. You’ll find it described as the “death carrot’’ in online accounts.
Thapsigargin kills fast-growing cells. So far, so good; that’s a routine property of chemotherapy drugs. But the relative safety of classical chemotherapy agents rests on the fact that they’re more destructive to rapidly multiplying tumor cells than they are to slow-growing normal cells.
Thapsigargin doesn’t work that way—which initially made it alarming to Dionne’s friends. It’s an equal opportunity cell-killer.
“It can kill cells that grow slowly,” Dionne says. That makes it a threat to normal cells, unless a drug company can successfully tweak it. And Dionne saw a reason to try.
Like most normal cells, some cancer cells also grow slowly, such as those in tumors of the prostate. And such cancer cells can resist chemotherapy drugs that target fast-growing cells. Dionne and his collaborators at Johns Hopkins reasoned that thapsigargin might be an effective weapon against slow-growing tumor cells, if it could be modified to spare normal cells. The end result of their chemical tinkering is GenSpera’s experimental drug G-202, which has now moved into a second round of early stage clinical trials.
The compound was designed to allow the powerful toxin to move through the bloodstream in an inactive form until it’s released by an enzyme, PSMA, found at higher levels on the surface of certain tumor cells, Dionne says. He compares G-202 to a grenade with a pin ready to be pulled.
A molecule of G-202 contains a modified form of thapsigargin called 12ADT, which is linked to a small peptide. The effect of that peptide—a small chain of five amino acids—is to keep 12ADT soluble in the watery environment of the blood. More importantly, … Next Page »