In a recent paper in Nature, researchers Rudolf E Tanzi and Doo Yeon Kim of Massachusetts General Hospital detailed the way in which they were able to cultivate human brain cells in a gel matrix. The cells have genes inserted into them so that they develop both plaques and the tangles—cell deformities that are characteristic of the disease. It’s the closest in vitro model to the disease yet developed. The best that researchers have had to work with to date has been a mouse model, both in vitro and in vivo. The mouse cells develop only an imperfect version of the disease (they develop the plaques but not the tangles), and working with whole mouse brains is both expensive and time consuming.
Quantum leap in speed
The new technology could offer a quantum leap in the speed with which new therapies, both in terms of drugs and natural alternatives, can be tested and refined, said experts. One of them, Tom Shea, PhD, a professor of biological science at the University of Massachusetts, Lowell has been studying the disease and natural ways to ameliorate its effects for decades. Some of that time might have been saved if the groundbreaking human cell culture technology had been available, he said.
“It’s very exciting scientifically. It opens up some new possibilities for speeding up the testing of compounds. If I had had this culture 20 years ago it would have saved me a lot of time. Using a mouse model is painstakingly slow; it takes about a year to see a result,” Shea told NutraIngredients-USA.
The new human cell culture looks at two prominent aspects of Alzheimer's disease that concern the function of two proteins: beta amyloid and tau. In the case of the first protein, excess production results in the formation of plaques, and in tau pathology the cells develop spaghetti-like strands called tangles. Shea said it is unknown whether these structures are damaging in and of themselves or whether they are the result of the cell trying to protect itself from damage. In any case, the appearance of the structures is strongly correlated with decreased cognitive function and memory impairment.
Streamlined testing of multi-ingredient formulas
Shea was involved with the development of a dietary supplement that addresses cognitive decline. The finished formulation is on the market branded as Perceptiv, and is a combination of six ingredients: Vitamin E, folic acid, Vitamin B12, N-Acetyl-L-Cysteine, Acetyl-L-Carnitine and S-Adenosyl Methionine (SAMe). When starting work on the formulation, Shea said he and his team worked with ingredients alone and in combination, with each test eating up chunks of time.
“We started working with the individual constituents of the formulation and then in combination. We could see in the cell cultures how much beta amyloid was produced with each intervention. With the new technology, in rapid-fire succession you could screen new compounds. It could definitely be a time saver,” Shea said.
Other experts in the field of dietary supplement ingredients shared Shea’s hopeful outlook on the new technology. The new approach could offer way to test approaches to ameliorate the symptoms of existing disease as well as offer a way to test preventive measures, they said.
“From the standpoint omega-3s, where we think the benefit is the prevention of disease, we think this could be a very good model,” said Harry Rice, PhD, vice president of regulatory and scientific affairs for the Global Organization of EPA and DHA Omega-3s (GOED). “You could test a broad array of supplements. It could give a quick indication of whether you are barking up the wrong tree.”
“What this really opens up is the opportunity to better explore mechanisms. I can see a benefit on both the negative and positive side,” said Michael Lelah, PhD, chief research scientist at mercola.com. “On the negative side, you could introduce a whole bunch of toxins to the cells, things like various metals or pesticides, and after observing the effects on the cells there could be the opportunity to recommend lifestyle changes. On the positive side it could support the development of new drugs or natural products that could intervene or support the prevention of Alzheimer’s.”
A better model—but still a model
The model’s three dimensional aspect is one of the key benefits of the breakthrough, Shea said. Cells behave differently when cultured on a two-dimensional medium, and the excess beta amyloid tends to leak away instead of forming the Brillo-like structure referred to as a plaque. Still, Shea and others cautioned that the new model, while exciting, is just that: a model, not the real thing.
“The downside is that these are brain cells in a culture dish. That means we are really far removed from a human brain. It is a chance to study mechanisms, but what works in the dish may not translate quickly to a human,” he said.
Jennifer Gu, PhD, vice president of research and development for ingredient supplier AIDP, also raised concerns with how the researchers induced the cells to make the plaques and tangles and what that means for the model’s transmission into in vivo processes.
“By introducing a mutated gene into the system to create a model of disease, it already assumed that the disease is caused by the mutation of the gene. This assumption is not true for most of the cases in human Alzheimer’s. Thus, agents work in this model may still have issues in humans,” she said.