Petri Dish Breakthrough May Hasten Search for Treatments and a Cure

October 13, 2014

A team of Boston scientists have discovered a way to grow human brain cells in a petri dish, which will open the door for much faster testing of Alzheimer’s drug candidates.

By Sam Gaines

They’re calling it “Alzheimer’s in a dish.” Lead researcher Dr. Rudolph Tanzi of Massachusetts General Hospital in Boston and member of the Fisher Center for Alzheimer’s Research Scientific Advisory Board, on a suggestion from colleague Doo Yeon Kim, and his team have pioneered the growth of human neurons (brain cells) in a petri dish, where Alzheimer’s disease treatments can be studied much more quickly than ever before. That’s because the human neurons actually develop the telltale plaques and tangles that characterize Alzheimer’s when genes that code for Alzheimer’s disease are introduced, and they do so in a matter of weeks.

The research was published in the October 12, 2014 issue of Nature.

Using this new technique of growing brain cells in a petri dish, researchers will now be able to study treatments much more quickly than they could before, when only mouse brain models were available. “A lot of times when we are coming up with hypotheses for studying this disease, the verification of these hypotheses involves mouse work that can take a year, a year and a half, which is how long it takes the mouse model to develop the disease,” says Dr. Jean-Pierre Roussarie, a Senior Research Associate in the laboratory of Dr. Paul Greengard at the Fisher Center for Alzheimer’s Research at The Rockefeller University in New York. “This brain cell culture will reduce the delay of waiting for that to happen, so we can study much more in a much shorter period of time.”

Dr. Tanzi and his team used human embryonic stem cells and needed chemicals to create neurons in the gel. The team then introduced genes that are linked to the development of Alzheimer’s disease, and they witnessed the development of beta amyloid plaques among the neurons. While the neurons do not perfectly mimic their in-brain counterparts in human brain tissue, they do provide a much more accurate model for testing than the mice models used previously. In fact, efforts to reproduce Alzheimer’s in mouse brain tissue would yield plaques, but never the accompanying tangles known to occur in human brains with Alzheimer’s disease.

“There are technological aspects and advances that this paper introduces, but the paper also presents scientific data per se that confirms the beta amyloid hypothesis. This hypothesis states that the pathology starts with the appearance of the plaques, that then trigger the formation of neurofibrillary tangles (Tau aggregates),” says Dr. Roussarie. “Dr. Tanzi shows that the generation of amyloid plaque is preceding the generation of Tau tangles, and is necessary for it, beautifully demonstrating the amyloid hypothesis. There was data supporting this hypothesis already, but never as convincing as this, in such a simple, controlled model.”

The importance of this research is difficult to overstate, according to Dr. Sam Gandy of the Icahn School of Medicine at Mount Sinai in New York. Dr. Gandy completed his post-graduate work under Dr. Greengard at the Fisher Center. He told the New York Times that the research is “a real game changer” and “a paradigm shifter.”

Nobel Laureate Dr. Paul Greengard, Director of the Fisher Center for Alzheimer’s Research, is also very excited about the research and its implications for the future of Alzheimer’s research. “I want to extend my warmest congratulations to long-term friend and colleague Dr. Rudy Tanzi on his publication in Nature. He managed to grow neuronal cells in an in vitro system where they recapitulate the two main features seen in patients with Alzheimer’s disease: amyloid plaques and neurofibrillary tangles, the two different kinds of protein aggregates that devastate the brain,” Dr. Greengard says. “This new fantastic tool will help Alzheimer’s research tremendously: It will be an amazing platform for screening new drugs much faster than what was possible before in order to find promising candidates. But it will also help testing hypotheses about the mechanism of the disease much more easily, in order to better understand Alzheimer’s. I cannot wait to use this model in future collaborative projects with Dr. Tanzi.”

Kent Karosen, President of the Fisher Center for Alzheimer’s Research Foundation, heralded the results of the study as a major breakthrough in the search for better treatments and a cure for Alzheimer’s disease. “This vital development means that the beta amyloid hypothesis, which has been the focal point of our efforts in the Fisher Center laboratory, is the correct approach in Alzheimer’s research, as it clearly marks the connection between plaques and tangles,” he says. “This level of scientific innovation is why funding for Alzheimer’s research is critical. Our next step is to focus on creating and testing drugs in this new system to help Alzheimer’s patients.”


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