Breakthrough at MGH Aids Alzheimer’s Research
On October 12, 2014, researchers from the Massachusetts General Hospital published a breakthrough in the journal Nature. The team announced they were able to grow human cells with the same characteristics as a brain with Alzheimer’s disease: hard clumps called plaques and coils known as tangles.
Lead researcher Rudolph E. Tanzi of Massachusetts General Hospital attributes their success to a suggestion by colleague Doo Yeon Kim to grow the cells in a gel. In a three-dimensional culture system, the human neural stem cells were able to form networks as in a real brain.
After adding to the petri dish two genes known to lead to Alzheimer’s – an amyloid precursor protein and presenilin 1 – the team waited for growth.
Six weeks passed, then the cells were found to have grown significant amounts of both the normal form of beta-amyloid and the toxic form associated with Alzheimer’s
“Sure enough, we saw plaques, real plaques,” Dr. Tanzi said. “We waited, and then we saw tangles, actual tangles. It looks like you are looking at an Alzheimer brain.”
The researchers dubbed their product “Alzheimer’s in a Dish.” With this new asset, the scientists can “test hundreds of thousands of drugs in a matter of months,” says Dr. Tanzi.
The Alzheimer’s cells grown do lack certain components of the brain, such as immune system cells, which aid in increasing the dementia once Alzheimer’s has started. Still, this breakthrough will help researchers test preventative drugs.
Dr. Tanzi has started a sizable project to test 1,200 drugs on the market and 5,000 experimental drugs that have finished the first phase of clinical testing. The researchers can now test these drugs in petri dishes instead of using mice – a huge advantage, as testing with mice means each drug test takes a year.
This “Alzheimer’s in a dish” should also aid in more accurate drug test results. When researchers put the proper genes in lab mice, the animals developed the beta-amyloid protein, creating plaques, but they never developed tangles. Studies could not bridge this error. With no other options, researchers continued to use mice in their drug testing. Unfortunately, more than twenty drugs seemed to cure Alzheimer’s in the mice, but failed when tested in human patients.
Not only does this breakthrough aid in future research, but it has proven a hypothesis regarding the cause of Alzheimer’s. In the mid-1980s, Dr. George G. Glenner theorized that the protein beta amyloid was to blame. Others proposed that another protein, tau – a normal part of neurons that creates tangles in an Alzheimer’s patient – was the right target.
In this new study, Dr. Tanzi and his colleagues observed tangles forming with only amyloid plaques present. Thus it’s now known that this protein is at fault. Beta amyloid accumulates and turns into plagues, the plaques destroy signals between neurons, neurons respond by making tangles, and this process causes cell death, followed by dementia.
Knowing this, Dr. Tazi has already looked into drugs that block beta amyloid, preventing both plaques and tangles from forming. Some of these drugs are in clinical trials, but it is not yet known if they’re effective on humans.
Dr. Tanzi and his colleagues were also able to block an enzyme needed to make tangles after the plaques are present. This enzyme will be studied further as another potential drug target.
Separate from this drug research, Dr. Sam Gandy of the Icahn School of Medicine at Mount Sinai in New York hopes to use this Alzheimer’s breakthrough to study the effects of genes that predispose people to Alzheimer’s. He especially wants to focus on ApoE4, which contributes to roughly half of all Alzheimer’s cases. It is currently unknown how this gene is linked to the disease.
As of 2013, an estimated 44.4 million people worldwide suffer from dementia. With these new advances in Alzheimer’s research, scientists hope to see this number lower in the future.