June 13, 2007 |
A new test for toxicity may save researchers time and money, and allow a compound’s genetic toxicity to be tested much earlier in the drug discovery process.
Joe Shuga, a graduate student with appointments in the laboratories of three MIT faculty — Linda Griffith, Harvey Lodish, and Leona Samson — developed the assay. The results were published in May in Proceedings of the National Academy of Sciences.
Like the current FDA-approved toxicity test, the new test measures DNA damage in mouse red blood cells. The current test relies on injecting a compound into a live mouse and observing its effects on red blood cells produced by bone marrow. The new test looks for similar red blood cell damage, but in in vitro marrow cells.
Shuga tested DNA-damaging agents in his cell culture assay and compared the results to the outcomes from the current toxicity test. The results correlated well.
“The primary benefit early in drug discovery is [a test that is] potentially a lot cheaper and higher throughput than the current assay conducted in mice,” Shuga told Bio•IT World. If a pharmaceutical company wanted to predict whether a compound is going to give them some trouble in animal or clinical tests, this could be used as a valuable prescreen.
Second That Prediction
Griffith seconds his prediction: “This is a much cheaper assay that’s at least as predictive as previous assays, and drug developers can afford to use it a lot earlier in the drug development process.” The cell culture system will reportedly allow researchers to run hundreds of thousands of tests from the bone marrow of a single mouse. “Instead of testing one chemical and one dose in one animal, you’ll be able to take one animal, get the bone marrow out, and test a thousand different conditions,” says Samson.
And of course there’s the hope of eventually using human marrow cells to do the same tests. “This research is the first step in a new type of clinical drug toxicity test,” says Lodish, from the Whitehead Institute. “And although we haven’t done it, you may be able to extend the technique to humans.”
“If you could change the micronucleus assay to have a human cell readout, that would be pretty amazing,” says Samson. “The presumption is that... in vitro human models could be closer to in vivo human,” Shuga says. “That premise will be tested in coming years.”
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