Three discoveries in three weeks

HSCI researchers take giant steps in three different directions.

A hormone that just may prove to be the treatment for type 2 diabetes; a protein in the blood of young animals that can cause the failing hearts of older animals to return to a youthful state; and a new drug screening technique with the potential to revolutionize and reduce the cost of drug discovery...

Had Harvard Stem Cell Institute researchers discovered any one of these things within the past year it would be cause for celebration. In fact, HSCI teams published reports of all three of these breakthroughs within a three-week period this spring.

The run of announcements began with the publication of a paper by HSCI Executive Committee member Lee Rubin, PhD, and colleagues in which they revealed a new, stem cell-based, drug-screening technology that could reinvent and greatly reduce the cost of developing pharmaceuticals. The researchers have already found several compounds that are more effective in protecting the neurons killed in amyotrophic lateral sclerosis (ALS) than are two drugs that failed in human clinical trials after large sums were invested in them.

Rubin’s model is built on an earlier proof of concept developed by HSCI principal faculty member Kevin Eggan, PhD, who demonstrated that it was possible to move a neuron-based disease into a laboratory dish using stem cells carrying the genes of patients with the disease.

Shortly after the publication of the Rubin paper came the announcement that HSCI Co-scientific Director Doug Melton, PhD, and postdoctoral fellow Peng Yi, PhD, have discovered a hormone that holds promise for a dramatically more effective treatment of type 2 diabetes, a metabolic illness afflicting an estimated 26 million Americans. The researchers believe that the hormone, which they named betatrophin might, also have a role in treating type 1 diabetes, also known as juvenile diabetes.

“If this could be used in people,” said Melton, Harvard’s Xander University Professor and co-chair of the University’s Department of Stem Cell and Regenerative Biology, “it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year.”

The work was done in mice, and Melton noted that “we’re not interested in curing mice of diabetes, and we now know the gene is a human gene. We’ve cloned thehuman gene and, moreover, we know that the hormone exists in human plasma; betatrophin definitely exists in humans.”

Melton and Yi are working on next steps with a German biotech firm, which already has licensed betatrophin to Janssen Pharmaceuticals, a Johnson & Johnson company that is working to move it toward the clinic.

As if those two discoveries weren’t good news enough, HSCI Principal Faculty members Amy Wagers, PhD, and Richard
Lee, MD, announced that they had isolated a protein found in high concentration in the blood of young mice – but depleted
in old mice – that restores to useful function the enlarged, weakened hearts of old mice.

The researchers believe that the protein, GDF-11, may play a role in numerous aging processes. Doug Melton called the
discovery “huge,” saying that “it’s going to change the way we think about aging.”