Meet the 'Rock Star of Science' Obsessed With Stopping Alzheimer's

Meet the 'Rock Star of Science' Obsessed With Stopping Alzheimer's June 23, 2017
By Mark Terry, BioSpace.com Breaking News Staff

It’s not often that you hear optimistic opinions about Alzheimer’s drug research. The field is a wasteland of failed clinical trials. Yet one leading Alzheimer’s researcher, Rudolph Tanzi, is very optimistic, even telling Forbes, “I believe there is a significant possibility that we will have a solid plan for eradicating Alzheimer’s disease by 2025.”

Tanzi is the vice-chair of Neurology and director of the Genetics and Aging Research Unit at Massachusetts General Hospital. He serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School. He is the co-discoverer of three early-onset familial Alzheimer’s genes. And as the head of the Alzheimer’s Genome Project, which was supported by the Cure Alzheimer’s Fund, he helped identify several other Alzheimer’s-related genes.

Currently, Tanzi co-developed an Alzheimer’s drug with Steve Wagner of the University of California San Diego (UCSD) and the National Institutes of Health (NIH) Blueprint Neurotherapeutics Network. The drug will begin early safety clinical trials with the NIH by the end of this year. It things go the way they hope, it could be in patient clinical trials by the end of 2018.

The predominant work being done with Alzheimer’s drugs focuses on beta amyloid, which accumulates in the brain in Alzheimer’s patients. Other research focuses on tau, which are other types of protein tangles that appear in the brain later in the disease.

Tanzi’s compound is a gamma secretase modulator (GSM). Gamma-secretase is one of the enzymes that produces amyloid proteins (the other being beta-secretase). Early work with gamma secretase inhibitors completely blocked gamma-secretase. As Forbes writes, “The problem is that both of these enzymes have other important jobs such as cleaning out the old proteins from a brain nerve cell’s surface so it can remain healthy and functional. Scientists don’t want to block these important functions.”

Tanzi and Wagner’s GSM drug targets and regulates gamma secretase to prevent it from manufacturing amyloid, but that would still allow it to do its jobs.

Tanzi notes that there are currently three therapy classes for lowering amyloid levels in Alzheimer’s disease—Beta-secretase (BACE) inhibitors, antibodies to amyloid, and GSMs. “It could be one or a combination of any of these therapies,” Tanzi says. “Maybe we have a cocktail of drugs or just the GSM. But that’s how we’re going to eradicate Alzheimer’s. Based on safety, efficacy and price, I’m betting a GSM is going to win the day.”

There are currently about five million people in the U.S. with Alzheimer’s, and worldwide about 50 million. But with an aging population, the number is only going to grow. Aside from the obvious impact on individuals and families, the impact on the U.S. healthcare system if no new treatments are developed will be severe. Currently about 20 percent of Medicare and Medicaid funding is spent on treating Alzheimer’s or Alzheimer’s care, but there are 71 million baby boomers approaching the high-risk age for the disease. Tanzi told Forbes, “Alzheimer’s disease could single-handedly collapse our healthcare system.”

At a recent TEDx event, Tanzi said, “That 50 million is going to be what we have in this country if we don’t do something about this disease, because right now we’re treating the disease with drugs that temporarily affect the symptoms modestly—modest benefit for a short while.”

Part of Tanzi’s work with Doo Yeon Kim involves what Tanzi called “Alzheimer’s-in-a-Dish.” They use stem cells to create human nerve cells, which are then inserted into a gel to simulate the human brain. This is essentially a simulated human brain organoid that provides a three-dimensional neural culture network.

There has been some controversy of late over the amyloid theory, largely because drugs that seem to be effective at clearing amyloid don’t seem to reverse the disease. Tanzi, however, says the Alzheimer’s-in-a-Dish confirms the amyloid theory. “There is not a debate anymore,” he told Forbes. “All data say that if you keep the amyloid low, then you stop Alzheimer’s.”

He goes on to explain, “Every Alzheimer’s trial that targeted amyloid plaques failed. Brain imaging showed us that amyloid plaque build up is happening up to 10 to 20 years before any symptoms of dementia. So it doesn’t help them to lower the amyloid after the patient already has symptoms.”

With any luck for millions of patients with Alzheimer’s and their families, Tanzi’s drug will be the solution to a very knotty problem.

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