“Despite decades of study, the underlying cause of Alzheimer’s continues to evade scientists. Until recently, the only drugs available to patients targeted the symptoms of the disease, rather than underlying pathology.
The approval of the anti-amyloid drug Aduhelm marked a significant milestone in Alzheimer’s drug development. It is the first drug with the potential to modify the course of the disease’s pathology, and designed to halt or even stop disease progression.
Aduhelm’s efficacy, and therefore its FDA approval, is mired in controversy. However, other anti-amyloid drugs designed to function similarly — addressing the disease itself, not just the symptoms — are close behind it in the drug development pipeline. Two more — lecanemab and donanemab — recently received breakthrough status, meaning they’ll be fast-tracked for review by the FDA.
But what is the clinical relevance of the distinction between treating symptoms and modifying disease? And is this paradigm even useful?
Treating Alzheimer’s Symptoms
The symptoms of Alzheimer’s often appear 10 or more years after the disease itself starts.
By then, progressive cell death causes cognitive impairment, confusion, memory problems, trouble sleeping, and even changes in mood or personality. Catching these symptoms at an earlier stage, the first signs of mild cognitive impairment, is crucial for implementing lifestyle interventions, prolonging the quality of life, and preserving cognitive function for longer.
Many drugs are approved to treat these cognitive symptoms. For people with mild cognitive impairment or with early-stage Alzheimer’s, these symptomatic treatments can have a major impact on day-to-day quality of life.
However, the disease will continue to progress, and at moderate and severe stages, these treatments become less effective as brain cells continue to die.
While symptomatic treatments aren’t intended to target Alzheimer’s root causes, some have shown the ability to go beyond their initial “band-aid” intentions, and actually potentially slow the disease’s progression.
Galantamine (brand name Razadyne) is an Alzheimer’s drug developed with the intent to treat cognitive symptoms, and was approved for this purpose by the FDA 18 years ago. A recent study published in the journal Neurology found that, compared to other symptomatic treatments, Galantamine may also reduce the risk of severe dementia.
While researchers have yet to determine precisely why this is the case, there is some evidence that this drug increases amyloid plaque removal in the brain, just like the new wave of disease-modifying anti-amyloids that are currently in development. It is uncertain if this approach is ultimately the right one when it comes to stopping Alzheimer’s in its tracks.
Once researchers learn more about this mysterious disease’s underlying causes — either validating or moving on from the “amyloid hypothesis” under which drugs like Aduhelm, lecanemab and donanemab are being developed — there will be other hurdles to overcome. For one, these drugs are prohibitively expensive and as a result, the cost of Medicare premiums is rising for many Americans.
Many Alzheimer’s experts suspect that there is no “magic bullet” to Alzheimer’s due in part to its complex nature. There is much hope for new disease-modifying treatments, but treating and managing Alzheimer’s may require a personalized combination of treatments — those that modify the disease itself as well as drugs that treat its symptoms.
To learn about clinical trials of new medications that aim to modify the pathology of Alzheimer's disease, call Charter Research at 407-337-1000 (Orlando) or 352-775-1000 (The Villages).