Article from Dr. JoAnne McLaurin, PhD. Senior Scientist Sunnybrook Research Institute November 2020
Updates on Alzheimer’s disease research, diagnosis and treatments:
1. There is a blood test on the horizon that has shown very high selectivity for detection of Alzheimer’s disease patients over other dementias. The test has also been used in a cohort of familial Alzheimer’s disease patients, in which the onset of dementia in these families is known accurately. The blood test was able to detect the family members who carried the mutation causing Alzheimer’s disease 10-15 years prior to onset of symptoms. These latter results will need to be confirmed in other families that carry gene mutations resulting in Alzheimer’s disease. The development of this blood test has been in part from a research group in Montreal at the Montreal Neurological Institute whose collaboration with an international consortium is testing the efficacy. The results from this new test has the clinical and the research community very excited as it would eliminate the highly invasive tests that are presently necessary to give an Alzheimer’s diagnosis. It will also allow us to identify people at risk and thus start life-style interventions that have been proven to delay the onset of Alzheimer’s disease. These are stay both physically and mentally active including exercise, eating well, watching you blood pressure and glucose levels. What is good for your heart is good for your brain.
2. On the research front, a large number of laboratories around the world are now trying to develop better models of Alzheimer’s disease that will allow us to understand disease process and better test drug candidates. These new models are necessary because we now know that Alzheimer’s disease is multi-factorial contributors to disease onset and progression; thus we need models that have all these factors.
a. With new understanding in genetics and how genes are turned on and turned off, we can isolate blood cells from a patient and through multiple steps turn these blood cells into neurons with the persons genetic make-up and changes to their genes that develop over a life course. This allows us not only to start to address some of the variability we see between patients with Alzheimer’s disease but also in the longer term develop personalized medicines. All cells in our body come originally from what is called a “stem” cell which has the ability depending on the cues that it receives to turn into multiple different types of cells. Understanding these cues has allowed scientists to reverse engineer this process and make a blood cell back into a stem cell, called induced pluripotent stem cells. These induced stem cells can then be made into specific brain neurons by exposing the stem cell to the appropriate cues. As mentioned above, the “new” neurons contain all the genetic material and changes to that genetic makeup that has occurred over the patients’ lifetime.
b. New rodent models are being developed. These new rodent models will address the multiple pathologies that we now understand to occur in 90% of Alzheimer’s disease patients. For the last 100 years, we have focused on the presence of amyloid plaques and neurofibrillary tangles within the brain for Alzheimer’s disease patients. However, we now know that most people have mixed pathologies and may also express Lewy bodies, which we previously only associated with Parkinson’s disease or a protein called TDP43 deposits that are more typically associated with frontal temporal dementia in the past. My laboratory is heavily invested in developing both of these models, but we are in the early stages however preliminary data shows promise.
3. Lastly, I had delayed sending this update as I hoped to have some positive news in regards to a potential treatment. Biogen has developed an antibody called aducanumab which has undergone two phase 3 clinical trials. One of those trials was successful however the second one was not. However, with the need for some type of treatment for Alzheimer’s disease Biogen choose to submit a proposal to the FDA (Federal Drug Administration in the US) for approval. The process is quite complicated with the company assembling a report and handing over all raw data to the FDA. The FDA then independently reviews the report and data to determine whether one the data as presented is correct but also whether there is a case for benefit for in this case Alzheimer’s disease. There is then an open forum, which occurred last Friday November 6, that any interested group could attend online and those with a stake in the decision could address the committee. Unfortunately, the committee was completely divided with those in favour and equally those who thought the drug did not make the required benchmarks. This has left the FDA to pull back and it will reconsider the data- however- it leaves us in limbo until March 2021.
There are many advances that have occurred in the last year throughout the international research community. The ones I have listed above are in my opinion the biggest leaps in our advance towards not only understanding this disease but also treatments.