Alzheimer’s disease is a frustrating and confusing illness, not just to those who suffer from it and their loved ones, but also to those of us who study and develop treatments for this disease. While we understand much more about the underlying biological causes of Alzheimer’s disease, there is still more that we have to learn about how the disease begins, who is vulnerable, and what are the best approaches to prevention and treatment. While we have had many treatment failures and false starts over the last several decades, we have made major advances in developing new agents and approaches that I believe will pay big dividends over the next few years.
Much of our therapeutic research over the last decade has focused on ways to lower the levels of abnormal proteins in the brain that are associated with Alzheimer’s disease. These proteins, beta-amyloid and tau, appear to be tightly linked to the onset and progression of the illness, although the exact sequence of when they appear and how that initiates the course of memory loss and other problems remains uncertain.
Prevention and treatment approaches have focused on either reducing the production of these proteins or in clearing them from the brain when they do appear. Initial studies involved used antibodies to remove excess beta-amyloid from the brain of patients with mild-moderate Alzheimer’s disease. These studies have been partially successful in that removal of beta amyloid seems to occur, but that did not seem to change the course of the illness, which continued to progress. These failures have lead us to think that these amyloid removal approaches might work better if we intervened earlier in the course of the illness or attempted to prevent the disease from occurring at all. This has led to a number of ongoing studies that are administering the anti-amyloid medicines at the earliest identifiable stages of illness or to those who have no symptoms but are at high risk for the illness due to family history or genetic risk factors. We are excited to await the outcomes of these important studies.
Additional strategies are being investigated to potentially improve the symptoms or delay the progression of this illness. These studies focus on repurposing medications that may have been used for other purposes or developing new molecules that may stimulate the brain in ways that have not been possible before.
For example, here at Vanderbilt, we are leading a national study (supported by the National Institute on Aging) investigating whether nicotine may improve the memory and attention problems in patients with early memory loss, so-called Mild Cognitive Impairment (MCI), the stage of memory loss that precedes Alzheimer’s disease. While we associate nicotine with the negative effects of tobacco smoking, nicotine is a natural plant derivative that stimulates important areas of the brain that are involved in attention and memory. You can learn more about the study at www.MINDStudy.org.
Currently available medications for Alzheimer’s disease attempt to compensate for the loss of chemical systems in the brain that are involved in learning and memory, particularly the cholinergic system. However these medications have significant limitations and only modest benefits. We are developing a new molecule that will stimulate these systems in ways that will hopefully avoid many of the problems that previous treatment approaches have had. This new approach may significantly improve treatment of symptoms both early in the disease and in later stages as well. We are initiating human studies with our first drug later this year.
This is an exciting and promising time for treatment development in Alzheimer’s disease. Our knowledge and understanding of this illness has advanced rapidly and the design and implementation of clinical research studies is rapidly changing. I believe that these efforts will make a real difference in this disease over the next few years.
You can learn more about our efforts in this area at the Vanderbilt Center for Cognitive Medicine at: www.medschool.vanderbilt.edu/ccm/ . If you would like to learn more about advances in clinical trials in Alzheimer’s disease, check out: www.globalalzplatform.org