For the last two decades, researchers have been unable to find a drug to cure Alzheimer’s disease. Amyloid protein, also called Abeta, is thought to be the hallmark of Alzheimer’s. There have been many drugs developed that reduce or eliminate Abeta in mice, but that have repeatedly failed clinical trials in humans.

As scanning techniques improved, researchers realized that some people with Abeta accumulations did not develop Alzheimer’s. Some scientists began to question whether Abeta was in fact the key to unlocking the mysteries of Alzheimer’s.

In an article published two weeks ago in Nature, neuroscientists Doo Yeon Kim and Rudy Tanzi of the MGH reported that they have found a method of growing “Alzheimer’s in a dish”, and that this ability will answer long standing questions and tremendously accelerate the research for a cure.

 

Alzheimer’s in a Dish?

The MGH researchers created human brain neurons with Alzheimer’s in a laboratory, something that has not been done before. They took human embryonic stem cells, and bathed them in chemicals that turned these cells into brain neurons. These cells were grown not in a liquid medium, which has been the standard, but in a three dimensional gel, which closely resembles the environment in the human brain.

The researchers added two genes to the neurons, both of which are associated with early onset Alzheimer’s disease. Within 6 weeks, the neurons had developed Abeta protein clumps. Two to four weeks later, the neurons also had developed tangles. It was Alzheimer’s in a dish, and it could have profound implications for future research.

 

Confirmation of the Amyloid Hypothesis

As discussed in a previous blog, there has been a disagreement within the research community about whether Abeta is the cause of Alzheimer’s, since the presence of Abeta alone does not cause Alzheimer’s. The leading theory has been that Abeta deposits create inflammation or triggers other processes, which in turn causes the development of Tau tangles that do cause Alzheimer’s. However, this hypothesis has never been proven. Dr. Tanzi believes that, based on the development of Tau in a petri dish without the introduction of any other agent, Abeta alone starts the cascade that leads to Tau and Alzheimer’s.

 

A New Research Target

The MGH lab also thinks that it has discovered one reason why some people with Abeta deposits never develop Alzheimer’s. The lab discovered that there is an enzyme needed to convert Abeta plaques into Tau tangles – enzyme GSK3. The identification of this enzyme gives researchers another target in their quest to find a drug that will prevent Alzheimer’s.

 

Accelerated Research

Dr. Tanzi plans to test 1200 drugs currently on the market to determine if any of them are effective in stopping the cascade of protein growth that results in Alzheimer’s. He also plans to test another 5,000 drugs that have successfully completed Phase 1 clinical testing. He believes that he can complete this screening of drugs “in a matter of months”. Using mouse cells, it would take one year to test just one drug.

The ability to screen new drugs quickly will accelerate drug development by allowing researchers to focus only on those drugs that show efficacy using human neurons in the lab. Other research labs have called the MGH’s work “a real game changer” and a “tour de force”.

We have been hopeful before that researchers had found a cure, only to be disappointed. We are still waiting for that cure, but we now have a reason to be hopeful that a cure is closer than it ever has been.