The Future of Alzheimer’s Treatment
and why to be wary
Almost everyone can picture what Alzheimer’s disease (AD) looks like: forgetting things, getting lost, repeating the same sentences over and over. Most people can picture this because almost everyone has had grandparents with Alzheimer’s or knows someone who did. Many people think of it as a normal process of getting older, but it is much more than normal aging. Symptoms of late stage Alzheimer’s include losing the ability to communicate, walk, sit up, swallow, control one’s bowels and bladder, and it eventually leads to death. In fact, AD is the 6th leading cause of death in the United States. The most troubling part is that there are currently no treatments that can cure, prevent, or significantly slow the progression of the disease. There is strong incentive for pharmaceutical companies to research potential therapies, but there is a high risk in spending so much on this research. The main issue is that the science behind AD is not currently advanced enough for pharmaceutical companies to invest upwards of $1.3 billion on the research and development of a new drug. However, several companies have new medications undergoing clinical testing that will surely come to the market in the near future. These drugs are already gaining traction with the media which has labeled them as potential miracle cures.
The main problem is that no one knows for sure what causes Alzheimer’s disease. The scientific community currently believes in what is known as the amyloid hypothesis, which states that AD is caused by the buildup of a protein called amyloid-beta that kills brain cells at high levels. In a healthy brain, amyloid is created and cleared away by the immune system so it never accumulates to concentrations high enough to cause damage. Amyloid is found at high levels in nearly all AD patients, however, no one has been able to definitively prove that it is the culprit. The new drugs coming to the market, known as BACE inhibitors, aim to prevent the buildup of amyloid. They work by hindering the enzyme that creates amyloid-beta, and thereby, prevents it from reaching dangerous levels. This therapy seems viable, but there are several potential issues.
One problem is that the effectiveness of these drugs depends on the validity of the amyloid hypothesis. These drugs assume that amyloid is the sole cause of AD, but there is substantial evidence to support otherwise. Another hallmark of the disease is the presence of a second protein called Tau that forms tangles in the brain and could very well be the origin of AD mediated neurodegeneration. Tau could work alone or in tandem with amyloid to cause harm in the AD brain. Either way, if tau plays any role, then BACE inhibitors will have little effect on alzheimer’s patients.
Another potential issue is the possibility that once amyloid plaques form and the damage is done, clearing the amyloid-beta may not have much of an effect on the clinical symptoms. Since neurons cannot regenerate, once they are damaged by amyloid they are gone forever. Although BACE inhibitors could be a viable option for preventing further progression of the disease, they would not be able to reverse any memory loss that has already occurred. If this is true, then the media reports of these new drugs potentially curing Alzheimer’s disease may help to mislead patients. Therefore, since the science of AD is still in its infancy, it is imperative that doctors and patients view any emerging AD drugs with health skepticism.
Years ago, a similar sequence of events occurred when the scientific community largely believed in the cholinergic hypothesis which produced a line of research that resulted in many new medications currently on the market. The cholinergic hypothesis stated that AD was caused by a deficiency in the neurotransmitter acetylcholine which is vital in the formation of memories. There are currently four of these drugs on the market and all of them provide frequent side effects such as nausea, vomiting, diarrhea, dizziness, and headaches. Meanwhile, they have not been able to significantly relieve symptoms for most patients, nor prevent or slow the progression of the disease. Therefore, most patients stop using these medications after several months of receiving no therapeutic benefits. When these drugs failed to provide substantial benefits, the scientific community lost their support of the cholinergic hypothesis. If the same events occur for the amyloid hypothesis, then the next generation of AD patients will likely suffer unnecessary negative side effects from these drugs without any symptomatic relief.
