Distributing Hope: Glimpses of a Future Without Alzheimer's
Treatment targeting amyloid could potentially slow Alzheimer's symptoms in select individuals, according to research findings.
In an unprecedented discovery, researchers claim they've found evidence that employing biologic drugs to eradicate sticky beta amyloid plaques from the brains of those destined to develop Alzheimer's can forestall the disease. These groundbreaking results stem from a study conducted by the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU), involving individuals with rare genetic mutations that nearly guarantee they'll develop Alzheimer's.
Over a small group of participants, the study conducted over eight years demonstrated a remarkable 50% reduction in the risk of developing symptoms for those taking an amyloid-lowering drug called gantenerumab. This striking result, while not definitive, points to the potential of amyloid-targeted therapies in the battle against Alzheimer's.
Researchers involved in the study believe that, with early intervention and long-term medication adherence, the disease may bepostponed for years.
This long-awaited breakthrough is cause for excitement, but also fear. As funding for the study is on the line, researchers worry that participants could lose access to the study drugs, especially in countries where the medications have not been approved. Without the ability to keep these patients on the medications, researchers may never fully comprehend the drug's lasting effects, nor answer crucial questions about who exactly will benefit from these treatments.
The 1980s Discovery: Clogged Brains & Sticky Proteins
The discovery of sticky plaques made from beta amyloid proteins and toxic tangles of tau in the brains of Alzheimer's patients in the 1980s spurred researchers to seek therapies that could clear these damaging proteins. Biologic medications designed to recognize and remove beta amyloid proteins have been tested for decades, but results have mostly fallen short.
In late-stage clinical trials involving over 1,800 people with early Alzheimer's, the white rabbit was gantenerumab: it slowed the progression of symptoms compared to a placebo, but the result was not statistically significant, leaving it the brinks of dismissal. Two other similar drugs, lecanemab and donanemab, did meet the US Food and Drug Administration's criteria, earning their approval for treating Alzheimer's patients with mild symptoms.
Despite their modest benefits, these pricy medications still find themselves underutilized, as their uncertainty makes some physicians and patients hesitant to employ them.
Unyielding Determination: Standing Up to Alzheimer's
Participants in the DIAN study, which began back in 2008, are affectionately known as the X-Men among themselves. This name is fitting for individuals who, though mutants, have committed themselves to saving the world from the scourge of Alzheimer's.
Sue, a study participant from Texas, explains her reasons, "I joined the study shortly after I found out that I and three of my siblings had a gene mutation that made it almost certain they would develop early-onset Alzheimer's disease. Of six children in my family, two brothers and two sisters have the mutation. One brother was tested but doesn't have it, and another brother doesn't want to be tested but remains free of symptoms. Two of my brothers and a sister developed symptoms around age 57. I, who at 61 am the youngest, haven't."
Her hope is not merely for scientific understanding, but for her own extended health and survival. "I truly believe that [the medication] has held off the disease for about four years for me."
Hope Amidst Funding Turmoil
While this research holds great promise, it is fraught with financial instability. Meetings to review the study's National Institutes of Health grant funding have been canceled twice, jeopardizing the continuation of the study and leaving participants in a precarious position. "It ends up becoming a really difficult position we're in, and that the participants are in," says Dr. Eric McDade, who led the study.
The stakes are high for all involved. In the absence of research funding, participants could gain access to study drugs, particularly in countries where the medications are not yet approved. Without the ability to keep these patients on the medications, researchers may never learn the full extent of the drug's effectiveness or discover the critical questions about who will be helped by these treatments.
"Keeping that group that has been on the amyloid drugs the longest is absolutely critical," says McDade.
Long-term Advancements in Alzheimer's Research
Since the 1980s, research into Alzheimer's has progressed significantly. The hunt for therapies that could remove beta amyloid proteins has continued, with promises on the horizon for various treatments. The latest study adds to a growing body of evidence supporting the amyloid hypothesis, which posits that removing amyloid plaquesfrom the brain could delay or even reverse the disease.
However, it is important to note that this study, while showing promising results, is small-scale and lacks a placebo control group, factors that may affect the overall interpretation. As research continues, the benefits and limitations of these therapies will become better understood.
Despite the uncertainties, the field of Alzheimer's research is moving ever closer to finding effective treatments, and the brave individuals who have committed themselves to the fight are bringing us closer to a future where Alzheimer's is not an inescapable death knell but instead a manageable, curable disease.
Additional Insights
Future Breakthroughs
- Researchers are exploring a variety of approaches to target Alzheimer's, from tau-focused strategies to stem cell therapies.
- The search for biomarkers that can identify those at risk for Alzheimer's is also underway, with the potential to diagnose the disease earlier and determine the effectiveness of treatments more accurately.
Current Anti-Amyloid Therapies
- Aducanumab (Aduhelm) was the first FDA-approved drug specifically for Alzheimer's in 20 years, targeting beta amyloid plaques to mitigate the disease's progression. However, concerns about its high cost and uncertain efficacy have led to ongoing debates and discussions.
Genetic Testing and Ethics
- As testing for genetic mutations linked to Alzheimer's becomes more accessible, questions about informed consent, privacy, and the implications of genetic testing grow increasingly prominent. Reflecting on her own experience, study participant Sue states, "I still feel like, fundamentally, I'm doing it to help the science, but at this point, it's helping me." This sentiment, however, raises important ethical questions about the potential burdens placed upon study participants.
Alzheimer's Global Impact
- The World Health Organization estimates that there are approximately 50 million people worldwide living with dementia, and that number is expected to triple by 2050. Addressing Alzheimer's is not only a global health concern, but also a pressing economic issue, as the associated costs are projected to reach $2 trillion annually by 2030.
- Believethat the subset of individuals with rare genetic mutations, who participated in the DIAN study, have held off Alzheimer's symptoms for years thanks to biologic drugs that target beta amyloid plaques, such as gantenerumab.
- Although amyloid-targeted therapies like gantenerumab, lecanemab, and donanemab have shown some promise, governments and health authorities must ensure the continuous funding of Alzheimer's research to understand their lasting effects, answer crucial questions about who will benefit from these treatments, and ultimately develop more effective dosages for a larger subset of patients.
- Regarding future breakthroughs, researchers are actively pursuing a variety of strategies to tackle Alzheimer's, including tau-focused approaches and stem cell therapies, in hopes of finding better treatments and biomarkers to diagnose and monitor the disease's progression in a larger subset of the population.
