MGH investigator Tanzi claims breakthrough will 'revolutionize' Alzheimer's R&D

Rudy Tanzi

Massachusetts General Hospital investigator Rudy Tanzi says he's figured out Alzheimer's, creating a new 'Alzheimer's-in-a-dish' approach to growing brain cells that he claims provides clear proof of the much-debated amyloid hypothesis as well as a solid target for the disease. And now he reportedly plans to race ahead with his new research process to find a potential megablockbuster drug that can stop the disease in its tracks.

Working with co-senior investigator Doo Yeon Kim, Tanzi is making some assertions that could upset the entire R&D field for Alzheimer's--if they're proven in upcoming research work. And he's been attracting some big headlines for the bold but risky proclamation.

The problem with Alzheimer's research, say Tanzi and Kim, is that investigators have traditionally relied on the fundamentally flawed approach of using mouse models for the disease. Now they've developed a new approach to growing brain cells in the lab that promises to "revolutionize" Alzheimer's research.

According to their release, Kim "realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the MGH team used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes--the amyloid precursor protein and presenilin 1--known to underlie early-onset familial Alzheimer's disease (FAD). Both of those genes were co-discovered in Tanzi's laboratory."

The stem cells first developed amyloid beta plaque, which is found in the brains of Alzheimer's patients, and then went on to form the tau tangles that also characterize the disease. By inhibiting an enzyme called GSK3-beta--known to phosphorylate tau in human neurons--they stopped the development of amyloid as well as tau. And Tanzi tells the New York Times that he's cycling through a huge number of drugs to find just the right one to tackle Alzheimer's, a memory-stealing disease that afflicts millions of people.

If he's right, Tanzi may be on the threshold of finding a drug that could be worth billions. But the Harvard professor's previous insights about Alzheimer's have run into some serious setbacks.

Alzheimer's is a perplexing and controversial field that has defeated dozens of serious attempts to develop new drugs that can either blunt the development of the disease or stop it. Tanzi himself is the scientific founder of Prana Biotechnology ($PRAN), a tiny company with a market cap of $88 million that recently claimed to see great success in a failed Phase II study of a novel Alzheimer's drug inspired by Tanzi's work on the role of zinc and copper balances.

Back in March, Prana's drug--PBT2, which promised to address the disease by triggering a chemical balancing act in the brains of Alzheimer's victims at a prodromal or early stage of development--failed the primary endpoint of reducing signs of amyloid beta and it failed the secondary endpoints of brain activity, cognition and function compared to a placebo. Prana's shares collapsed in the rout that followed.

Tanzi and Kim, though, are getting some major league endorsements from the scientific world for their new work, which was published in Nature. New York Times scribe Gina Kolata--who clearly scored an advance peek at the study--found some high-profile scientists willing to champion the advance.

"It is a giant step forward for the field," Duke investigator P. Murali Doraiswamy told Kolata. "It could dramatically accelerate testing of new drug candidates." Mount Sinai's Sam Gandy, who sits with Tanzi on the research consortium for the non-profit Cure Alzheimer's, which funded the work, also praised the effort. 

Cure Alzheimer's provided $3.35 million in 2012 to fund Tanzi's lab, by far the largest single beneficiary outlined in the group's form 990, filed with the IRS.

"This new system--which can be adapted to other neurodegenerative disorders--should revolutionize drug discovery in terms of speed, costs and physiologic relevance to disease," says Tanzi in a statement. "Testing drugs in mouse models that typically have brain deposits of either plaques or tangles, but not both, takes more than a year and is very costly. With our three-dimensional model that recapitulates both plaques and tangles, we now can screen hundreds of thousands of drugs in a matter of months without using animals in a system that is considerably more relevant to the events occurring in the brains of Alzheimer's patients."

- here's the release
- here's the story from the New York Times

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