Mouse models of a particular condition such as cancer are often the test subjects for drug therapies long before clinical trials begin. However the question of whether or not mouse results are meaningful in the search for effective drugs is still hotly debated in scientific research, both in universities and industry. Some camps believe that yes, mice with genetically engineered features of a particular diseases or condition are valuable in narrowing down drugs to proceed to human clinical trials; other camps believe that no matter how sophisticated a mouse model of a particular disease is it will never replicate the human condition and therefore using these to test drug treatments is not helpful. Now the Boston Globe reports that Dr. Pier Paolo Pandolfi of Beth Israel Deaconess Medical Center in Boston has leveled the playing field in a research study that gives drugs to humans and mice at the same time. The goal is to better integrate what is learned about a new drug from the mouse with what is learned from the human. Dr. Pandolfi first used this strategy successfully 15 years ago to develop treatments for then untreatable rare acute promyelocytic leukemia. The value of the ‘co-clinical trial’ approach is that it allows many more drugs to advance through testing at once, particularly combinations of drugs. And by using mice with different genetic mutations, researchers might predict which drugs should work in which patients.
Cheryl Marks, associate director in the division of cancer biology at the National Cancer Institute is quoted as saying “our traditional clinical trial structure . . . is simply not serving us very well.’’ Supporting this new approach is certainly an exciting way of implementing change; and Dr. Pandolfi received a $4.2 million National Cancer Institute grant through economic stimulus (ARRA) funding last year and a further five-year, $3.75 million grant.
Neurofibromatosis research too has the advantage of having a roster of very well developed genetic mouse models replicating all aspects of NF from bone dysplasia, learning disabilities to individual tumor types. The philosophy of testing drugs in more than one mouse model at a time is one utilized in the Children’s Tumor Foundation NF Preclinical Consortium in which drugs can assessed in up to six tumors of NF1 and NF2 in parallel making sure each drug receives as thorough an assessment as possible. It is an exciting prospect that we might utilize these models as a partner for future clinical trials.
