February 04, 2014

Drug-resistant TB underestimated, Cassell says

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As tuberculosis kills one person every 10 seconds, Gail Cassell, Ph.D., works to spread an alarm.

bio-gail-cassell“I want to impart to you a great deal of urgency with respect to developing TB drugs,” she said at the 5th biennial Southeastern Mycobacteria Meeting, held at UAB Jan. 24-26, 2014.

Cassell, former chair of the UAB Department of Microbiology, left to work at Eli Lilly and Company in 1997 until her retirement in 2010, establishing and leading the Lilly TB Drug Discovery Initiative. But even though Lilly has invested more than $150 million in this philanthropic effort and others have joined in a global TB alliance, the future looks grim.

Mycobacterium tuberculosis bacteria have mutated into a multi-drug-resistant forms (MDR-TB), and then into extensively drug-resistant TB (XDR-TB).

The magnitude of MDR-TB, Cassell said, is grossly underestimated, less than 10 percent of cases are being treated and the untreated patients continue to spread the resistant organism. Researchers expect an inevitable rise of totally drug-resistant TB, or TDR-TB, a pathogen that cannot be treated.

Cassell warned researchers attending the Southeastern Meeting that the TB drug discovery pipeline has very few active candidates in the early development phase and none in Phase I trials. The existing candidate drugs lack chemical diversity, lack target diversity and have significant cost issues. This is important because treatment requires a cocktail of at least three to four new drugs with different mechanisms of action.

Cassell has promoted collaboration and open scientific sharing among the less developed nations of the world where the burden of TB is greatest. Recent good news, she said was an agreement by the BRICS nations – Brazil, Russia, India, China and South America – to collaborate on TB treatment and control.

Spreading her message has taken the former UAB researcher to Russia, China, Kazakhstan and South Africa, to name a few of her stops.

“TB,” Cassell said, “has taken me to the ends of the earth.”

Contributed by Jeff Hansen for the UAB School of Medicine