Written by: Vindya Senanayake
Edited by: Esther Swamidason
Alzheimer’s disease (AD) is a type of dementia that starts with mild incidents of memory loss. As it progresses, it hinders the individual from responding to external stimuli and carry out daily activities. The despairing situation of this condition is not being able to communicate. Eventually, patients lose the ability to recognize their loved ones until they become strangers in their own lives. As of now, we have a limited number of treatment options that encircle controversy. However, the future of Alzheimer’s disease treatment has hope due to growing technologies and innovations. This article will detail you on the currently available treatments for AD and what the future of treatments may look like with the growth in research.
What is the disease burden?
Scientists consider the disease to be quite complicated because the prognosis of the condition varies from person to person. The main cause for the condition is the build-up of proteins in the brain. This includes the amyloid and Tau proteins that form plaques and tangles that disrupt normal brain functioning. Other contributing factors include age, genetics, lifestyle, and diet that can play a role in leading to this condition. Symptoms begin to appear after the age of 60. But, the brain chemistry starts altering as early as 20 years before the onset of symptoms.
What drugs are available?
Few treatments are out there to reduce brain cell death and regulate brain chemicals. However, none target the root cause of the problem of forming plaques in the brain. Recent inventions brought to life two drugs named Aducanumab and Lecanemab. These drugs individually work to remove pre-formed amyloid plaques and prevent the formation of more plaques. They are helpful in treating a daring condition that robs the lives of millions of individuals every year. We can look at them as the foundational solutions for the future of Alzheimer’s disease treatment.
- Lecanemab
Two pharmaceutical companies in Japan and the USA are actively developing Lecanemab, an FDA-approved drug. It addresses the buildup of amyloid plaques in the brain. Leqembi is the planned market name for this groundbreaking, first clinically proven treatment for Alzheimer’s. The idea behind Lecanemab is to reduce the speed of cognitive impairment. However, to achieve a positive effect, one must administer the drug early. This is successfully accomplished because as a monoclonal antibody, it specifically binds to amyloid beta proteins. Also, it can be easily administered intravenously.
- Aducanumab
Aducanumab, also known as Aduhelm is the preceding drug approved by the FDA in 2021 for the treatment of Alzheimer’s. This received a lot of backlash from the community as it followed the fast-track approval process by the FDA despite receiving strong objection from the FDA’s scientific advisory panel. Experts believe this results from the lack of positive cognitive decline results. Later, it became apparent that the Aducanemab faced an 8-1 vote against its approval. Three members of the advisory committee later resigned in order to uphold their disapproval of the drug, as it had been significantly disregarded. Since then, both the FDA and Biogen have faced scrutiny, raising concerns about their misguidance and protocol disregard. However, no party faced penalties.
What is the controversy and could it affect future treatment innovations?
We all remember the controversy that we experienced with the fast-approved vaccines to treat the COVID-19 pandemic. Similarly, the fast approval process of Lecanemab left people second guessing and having to weigh out the benefits and risks. Although designed in theory to improve cognitive impairment in individuals, it lacked clinical data to prove this prior to FDA approval.
The pharmaceutical duo requested FDA approval based on phase II data, which showed a reduction in plaques in 856 patients without assessing their cognitive improvement. To prevent another major disagreement from the advisory panel as during the approval of Aduhelm, the FDA went ahead with the approval process forgoing the hearing of the advisory panel. However, following the approval, the pharmaceutical duo released phase III data which shows the decline of cognitive impairment of the treatment group of 1800 individuals by 27% over 18 months.
The failure to wait for the phase III results before proceeding to its approval is one of the reasons for the controversy behind Lecanemab, apart from the deaths reported following the administration of the drug. Three individuals who initially received the placebo requested and were administered the actual drug during the phase III trial. Researchers believe that these three individuals experienced fatal brain hemorrhages and seizures as a result of a condition known as amyloid-related imaging abnormalities (ARIA). ARIA represents a spectrum of symptoms observed in patients receiving immunotherapies that target protein complexes in Alzheimer’s disease.
It is under the assumption of researchers that antibodies could have damaged the blood vessels while clearing out the amyloid plaques and thus resulted in a bleeding. Since patients in this clinical trial were receiving anticoagulants, which thin the blood, it could have potentially worsened bleeding in the other treated group. However, since this represents an isolated event, it would not be fair to make judgments solely based on it; nevertheless, it cannot be simply disregarded.
Although the cases were reported to the FDA, they did not change the primary decision to approve the drug for mild cognitive impairments. Furthermore, the FDA recommends issuing the drug with a clear warning about potential risks, including ARIA. Although the recent discoveries give us reasons to be hopeful, amyloid plaques are not the only driving force for Alzheimer’s. It is cause by an aggregation of events varying from inflammation, oxidative stress, and even build-up of Tau-protein. Thus, similar to complex resistant cancers, the best cause of treatment for Alzheimer’s would be a combination of treatments. However controversial, we should acknowledge that Lecanemab has opened doors for new approaches in the future of Alzheimer’s disease treatment. Also, it has paved the way for potentially more fruitful outcomes.
What is the future for AD?
The future of Alzheimer’s disease treatment is full of exciting possibilities. Scientists and doctors are working on new technologies that could change the way we manage this challenging disease. Technology holds the promise of revolutionizing how we approach this debilitating condition. As our understanding of the disease continues to evolve, several cutting-edge approaches are on the horizon.
- Precision Medicine: Advances in genomics and biomarker research are paving the way for personalized treatment plans. Tailoring therapies to an individual’s genetic and molecular profile could optimize effectiveness and minimize side effects.
- Immunotherapy: Building on the success and controversy of drugs like Aducanumab and Lecanemab, researchers are exploring new immunotherapies that target not only amyloid plaques but also other disease-related proteins like Tau. These treatments aim to slow or even halt disease progression.
- Nanotechnology: Engineers can design nanoparticles to deliver drugs directly to affected brain regions, bypassing the blood-brain barrier. This approach could enhance drug efficacy while minimizing systemic side effects.
- Neuroinflammation Modulators: Researchers increasingly recognize inflammation as a contributing factor in Alzheimer’s.Emerging therapies aim to regulate neuro-inflammatory responses, potentially slowing disease progression and preserving cognitive function.
- AI and Big Data: Machine learning algorithms can analyze vast datasets of brain imaging, genetics, and clinical information to identify patterns and predict disease progression. This can aid in early diagnosis and treatment planning.
In conclusion, the future of Alzheimer’s treatment is promising, with a diverse range of technologies and strategies under development. Continued research and collaboration will be essential to realizing the full potential of these emerging treatments. In the future, a combination of these technologies might bring us closer to better Alzheimer’s treatments. While we’re not there yet and though challenges and controversies persist, these innovations offer hope for a brighter future for those living with Alzheimer’s and their families.
