Alzheimer's Research Breakthrough Could Accelerate Development Of New Treatments

By C. Rajan, contributing writer

Scientists at Massachusetts General Hospital (MGH) have developed an ‘Alzheimer's-in-a-dish’ breakthrough, which will allow them to replace the current poorly performing animal models with an innovative laboratory culture system for studying Alzheimer's disease and discovering new treatments.

With this unique in vitro model of Alzheimer's, the researchers were able to replicate the process that leads to the development of Alzheimer's disease and confirm the existing hypothesis regarding the involvement of beta-amyloid plaques and tangles.

Lead researcher of the study, Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research Unit said, "One of the biggest questions has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call 'Alzheimer's-in-a-dish,' we've been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death."

To develop a realistic laboratory model of Alzheimer's in the brain, the team used a chemical gel to prepare the cell culture, instead of the typical liquid two-dimensional culture systems which do not properly represent the brain’s gelatinous three-dimensional environment.

The researchers then added pluripotent human stem cells (which can differentiate into any cell in the body) to the chemical-infused gel, and they were able to develop the stem cells into neurons and other brain cells. The brain cells were then treated with certain genes associated with Alzheimer's, and after a period of time, they formed networks as would be found in the human brain.

While the typically-used animal models do not replicate the human disease conditions accurately, the cells in the new culture system developed the signature plaques and tangles seen in human Alzheimer's patients’ brains.

This breakthrough will be a major help in understanding Alzheimer's disease and more importantly, in accelerating the discovery of drugs to treat Alzheimer's.

"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," said Dr. Tanzi.

The New York Times reports that Dr. Tanzi has already started using the new petri dish Alzheimer's model to test 1,200 currently available drugs and 5,000 experimental ones that have successfully cleared Phase 1 trials. While testing thismany drugs would take years with mice models, the new laboratory model will significantly speed up the discovery process.

Dr. Tanzi added, "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."

The full research paper can be found in the journal Nature.