Lost in the Translational

The first few times I heard the term “translational research” I cringed, assuming it referred to a complicated new concept that would be hard for me to understand.

To my ears “translational” sounded almost other-worldly, maybe something you’d read in a science fiction story. So I asked my wife, who has an MS and works in the scientific division of a pharmaceutical company, what she knew about it. “I think it has something to do with gene research,” she said. “But I don’t really know.” I knew it was time to look it up.

At the National Cancer Institute (NCI) website I found out there is a Translational Research Working Group (TRWG). And according to the TRWG, "Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce cancer incidence, morbidity, and mortality."

That pleased me no end. It was not complicated or hard to understand at all. But then I felt confused anyway: Hasn’t this been the goal of cancer research all along? Was I missing something in the translation? I looked at the flow chart and a depiction of “The Translational Continuum” posted on the NCI website. To me they both seem to describe a process of new drug development applicable to any therapeutic area.

But at least I thought I finally knew the meaning of “translational.” Then a couple of days ago I got an email about a “Translational Health Disparities Course” to be hosted by the National Institute on Minority Health and Health Disparities (NIMHD) in August on the campus of the National Institutes of Health (NIH) in Bethesda, Md.:

This two-week intensive course will provide specialized instruction on the concepts, principles, methods, and applications of health disparities science, practice, and policy. It will also integrate principles and practice of community engagement. Nationally and internationally recognized experts in health disparities science will lead individual sessions.

At first glance I didn’t see the “translational” connection, but after reading the email again I think I get it: You can identify health disparities and develop ways to overcome them, but those methods need to be put (“translated”) into practice if they are to have any effect.

Meanwhile, during my search for the meaning of “translational,” I found a press release about an article in a recent issue of a journal called (what else?) Translational Oncology:

“A drug developed at Linköping University in Sweden protects against the side effects of cancer treatments while strengthening the effects on the tumor.” Encouraging results of preliminary studies of the compound, known as calmangafodipir, were reported by Professor Rolf G. G. Andersson and colleagues. A larger group of patients is now being enrolled in an international trial.

The research stems from previous studies of mangafodipir, a substance used as a contrast medium in magnetic resonance scans, after pharmacologists at Linköping discovered that it also protected healthy cells in connection with chemotherapy treatments.

"We found that the substance could affect the formation of oxygen radicals, which are a cause of side effects in chemotherapy," said Andersson. For example, the number of white blood cells decreases drastically in almost all patients, which opens the door to potentially fatal infections.

When mice were treated with chemotherapy and simultaneously administered mangafodipir, tumor formation decreased while white blood cells were protected. The positive effect subsided, however, because a large portion of the manganese in the mangafodipir was released. The free manganese can also be poisonous and cause brain damage. The effect of mangafodipir was confirmed in a small study of patients with colon cancer.

"We remade the substance and replaced a lot of the manganese with calcium,” said Andersson. “This yielded a more stable complex, which turned out to be even better at protecting cells, thereby increasing the anti-cancer effect."

An international phase II trial involving patients with cancer of the large intestine has recently been initiated. Results are expected at the end of the year. The drug is being developed in Sweden by PledPharma AB, which plans to market it under the brand name PledOx®.

And if that isn’t translational I don’t know what is.

References:

• Karlsson JO, Adolfsson K, Thelin B, Jynge P, Andersson RG, Falkmer UG. First clinical experience with the magnetic resonance imaging contrast agent and superoxide dismutase mimetic mangafodipir as an adjunct in cancer chemotherapy-a translational study. Transl Oncol. 2012 Feb;5(1):32-38.
• Karlsson JO, Kurz T, Flechsig S, Näsström J, Andersson RG. Superior therapeutic index of calmangafodipir in comparison to mangafodipir as a chemotherapy adjunct. Transl Oncol. 2012 Dec;5(6):492-502.