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Director's Corner

Director’s Corner

Nov. 24, 2015: Making Surprise Family Connections

Christopher Austin

At this Thanksgiving time of year, we turn our attention to how very different our family members can be despite sharing the same genes. Diseases turn out to be like families this way — a discovery with profound implications for translational science.

Traditionally, doctors and researchers have organized their thinking about diseases around symptoms, or the organs and tissues they affect, rather than underlying biological mechanisms. By contrast, NCATS’ system-wide approach to translation starts with genetic or cellular mechanisms and considers what symptoms or diseases appear in any organ or tissue when those mechanisms break down. When applied to therapeutic development, this approach can lead to rapid advances via sometimes surprising connections, as it turns out that Mother Nature is the original “repurposer.” A given mechanism or pathway is often used to produce a variety of functions in different organs. Thus, a drug with a particular mechanism often can treat multiple different diseases, saving critical time and effort to get more treatments to more patients more quickly.

Recent studies supported by NCATS illustrate the potential of this mechanism-first approach. Several years ago, the pharmaceutical company AstraZeneca developed saracatinib, an investigational drug that blocks the function of a family of proteins called Src kinases, which are involved in cancer formation. (Src is short for “sarcoma,” a kind of cancer.) Clinical trials demonstrated that the compound was safe for cancer patients, but it did not appear to be an effective treatment.

Enter NCATS’ Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) program, which matches pharmaceutical companies with investigational drugs that have particular mechanisms with academic researchers who have ideas about other diseases that a drug with one of those mechanisms might treat. Although Src kinases were initially identified through their connection to cancer, more recent research shows their involvement in a neurological condition — Alzheimer’s disease — and a rare lung disease called lymphangioleiomyomatosis (LAM).

Two New Therapeutic Uses project teams are testing saracatinib as a treatment for both Alzheimer’s disease and LAM. NCATS-supported scientists at Yale University have shown that the compound reverses brain problems in a mouse model of Alzheimer’s disease and is safe in patients; a large trial of the drug’s effectiveness in Alzheimer’s disease is ongoing now. Additionally, NCATS-supported scientists at Baylor College of Medicine are testing whether blocking Src activity with saracatinib can reduce disease progression in LAM patients. If successful, these projects will have cut many years and millions of dollars off the cost of developing a new drug for these diseases.

This example — the potential of treating three different illnesses on the basis of a molecular characteristic they share — illustrates the importance and power of NCATS’ holistic approach to understanding health and disease and to developing new therapies. So as you sit down to your family’s Thanksgiving dinner with your seemingly disparate relatives, know that diseases also are being reconciled through unexpected biological connections they share, promising a rich translational harvest.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences