Rethinking why we don’t have a cure for Alzheimer’s

By Janet McMillan, C2ST volunteer and graduate student in chemistry at Northwestern University

For anyone who watches the nightly news on a regular basis, it would seem that one massive medical breakthrough after another has resulted in countless drugs available to cure Alzheimer’s disease.  These massively overstated headlines often fail to report that the drug in question has not yet demonstrated efficacy in improving memory in late stage clinical trails. Again and again, a promising drug that can cure Alzheimer’s in mice fails to produce positive results in clinical trails. Despite the large number of drug candidates making it to this point in the past few years, the only drug on the market currently, Mermantine, only produces short term memory benefits for patients. Dr. Grace Stutzmann, an Associate Professor in the Department of Neuroscience at Rosalind Franklin University tries to understand why so many of these drugs are failing to do what scientists think they will.

Over the course of Alzheimer’s disease “sticky”, or misfolded proteins build up in neurons, which prevent these cells from functioning normally.  Many drugs that have reached stage three clinical trials have been successful in clearing these misfolded proteins, but this has yet to result in a long term improvement in memory loss.  The underlying problem for research focusing on clearing these misfolded proteins is how poorly understood the link between memory loss and their build up in neurons is. Dr. Stutzmann, and many others in her field, believe that focusing on these misfolded proteins to find a cure could be the wrong approach since there is no direct link between their presence and memory loss.

Dr. Stutzmann takes the approach of studying how aspects of the brain that directly affect how neurons talk to one another, and therefore memory could be involved in Alzheimer’s disease and be new, and better drug targets.  Her group is trying to understand how altered calcium in synapses, the space that connects individual neurons and lets them talk to each other, can effect memory.  Changes in calcium will change how electrical signals move through the brain, and it has been found that this level of calcium is very low in those with Alzheimer’s disease.

Dr. Stutzmann and her team of researches have had some success is showing that using a drug that will restore calcium to its normal level can restore memory in animal models.  They remain only cautiously optimistic, however, since all the drugs that have failed in stage three clinical trails cured Alzheimer’s in mice, frogs, worms, and a myriad of other animal models.  Because of how poorly these animal models predict success of a drug in humans, Dr. Stutzmann is also working on developing models for Alzheimer’s using engineered human neurons, which she hopes will be a more representative system to screen compounds that can restore normal calcium levels.

Recent cuts in funding has made it a challenging climate for Alzheimer’s researchers in academic institutions, an issue that hyperbolic, and sometimes false science reporting of drugs that have not yet shown efficacy in human trails only worsens.  Despite the current lack of drugs with long term benefits and the ever increasing number of patients with the disease, Dr. Stutzmann remains enthusiastically optimistic that work such as hers will lead to many more advances in Alzheimer’s treatment.


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