Summer 2012 brought bleak news on Alzheimer’s experimental drug research. First, Pfizer’s drug bapineuzumab failed to perform as expected in late-stage clinical trials. A few weeks later it was reported that Eli Lilly’s drug solanezumab also wasn’t nearly as effective as hoped in late-stage trials. Research and trials on both drugs has now largely abandoned.
But the Alzheimer’s world received some good news last week when research published in the journal Neuron found that eliminating a specific enzyme from mice with symptoms of Alzheimer’s led to a 90 percent reduction in the compounds responsible for the production of the plaque that forms in the brains of Alzheimer’s patients.
The basics of the disease
Alzheimer’s disease is a condition shrouded in mystery. It has no definitive cause and no cure. It cannot be properly diagnosed conclusively except through an autopsy, but doctors have become better at diagnosing Alzheimer’s through brain imaging, blood work, a full medical assessment and family history.
Alzheimer’s disease causes nerves within the brain to die, resulting in tissue loss throughout the entire brain. Over time, this shrinks the brain and affects nearly every one of its functions.
A hallmark of Alzheimer’s disease is plaque made up of abnormal clusters of protein fragments that build up between the dying nerve cells. Scientists do not know if the plaque is a cause of Alzheimer’s disease or merely an effect, but they do know that the plaque is linked to significant and progressive cognitive decline.
A possible intervention
The subject of the new research from Ohio State University was the enzyme jnk3. Scientists found that jnk3 stimulates the production of A-beta peptides in the brain – peptides are proteins that are shorter in length –causing plaque to form. Not surprisingly, jnk3 activity is 30 to 40 percent higher in the brain of an Alzheimer’s patient than in a healthy brain.
With this in mind, scientists genetically deleted the jnk3 enzyme from Alzheimer’s disease model mice – mice that have the signs, symptoms and genetic mutations of early-onset Alzheimer’s disease. After six months, the mice that had jnk3 deleted saw a 90 percent reduction in A-beta peptide production. After 12 months, scientists still saw a 70 percent reduction in A-beta peptide production.
A closer look at jnk3
According to researchers, jnk3 is an enzyme that modifies its target proteins. Previous research found that the Amyloid precursor protein (APP), which produces the plaque building A-beta peptides, was somehow modified in brains with Alzheimer’s disease. What researchers did not know was that jnk3 does the modifying.
When jnk3 was deleted, according to the researchers, “the neurons’ overall protein production came very close to normal levels.” Essentially, jnk3 hindered the production between between the APP and A-beta peptides in the brain. Removing jnk3 allowed a normal path between the protein-peptide pair, and production resumed as normal without the A-beta peptides producing plaque on the brain.
The practical effects
But reduction of plaque buildup does not necessarily translate to a lessening of Alzheimer’s disease symptoms, which would be the goal of any drug therapy that could come from this research. So, scientists tested the cognitive function of the mice 12 months after the elimination of jnk3.
What they found was that eliminating jnk3 brought the cognitive function of the Alzheimer’s model mice to 80 percent of normal cognitive function, and increased the number of active neurons to 86 percent of normal. The Alzheimer’s disease model mice that did not have jnk3 removed only had about 40 percent of normal cognitive function and 74 percent of the normal amount of neurons at work in their brain.
What it all means
This new connection could be used to develop drugs that specifically target jnk3 as a means of Alzheimer’s intervention. As with any research of this nature, scientists are proceeding with cautious optimism.
Ohio State University (2012, September 5). Plaque-forming substances in mice with Alzheimer’s disease dramatically reduced. ScienceDaily. Retrieved from http://www.sciencedaily.com/releases/2012/09/120905122750.htm.
Alzheimer’s Association. Inside the Brain interactive tour. Retrieved from: http://www.alz.org/alzheimers_disease_4719.asp
Published On: September 14, 2012