Researchers are optimistic about new dementia treatments, with two promising medications—Lecanemab and Donanemab—showing potential to slow cognitive decline. Set for approval in the EU, these antibodies target harmful protein clumps in the brain. While they offer hope, the benefits vary among patients, and they are most effective when administered early. Ongoing studies seek to understand their long-term effects and explore preventive options, aiming to delay or prevent dementia onset altogether through early intervention.
Hope on the Horizon for Dementia Treatments
Researchers in the field of dementia are embracing a renewed sense of optimism. After facing numerous challenges like therapy setbacks, dwindling research funds, and skepticism from major pharmaceutical companies, two promising new medications have emerged. While these drugs do not cure dementia, they have the potential to significantly slow cognitive decline and may even serve as a preventive measure.
Upcoming Availability of New Medications
One of these groundbreaking medications is set to become available in the EU soon, following a positive recommendation for approval from the expert committee of the European Medicines Agency (EMA) in mid-November. In Germany, it could be administered in hospitals and clinics as early as February. Meanwhile, in Switzerland, both doctors and patients are awaiting a decision from Swissmedic as of December 2024.
Following the lead of the USA, China, and several other nations, approximately 13,000 patients worldwide are currently receiving treatment with these new medications. Since mid-2024, the second medication has also been accessible in the USA and other regions.
These medications feature a specific antibody: either Lecanemab or Donanemab. Administered intravenously every two weeks, both antibodies target undesirable protein clumps that form in the brain. These toxic formations accumulate around nerve cells over time and can lead to their degeneration, resulting in the cognitive deficits associated with dementia.
So, how do these antibodies help slow dementia progression? Research indicates that when antibodies attach to these protein clumps, they signal the brain’s waste disposal system to remove them, thereby slowing down nerve cell death. However, it remains unclear why the process does not entirely halt, as stopping nerve cell loss would be even more beneficial.
Despite their promise, the two antibodies are not miraculous solutions. They effectively reduce the presence of protein clumps in the brain, but not all patients experience the same level of benefit. While some report a significant slowdown in cognitive decline, others may continue to lose cognitive abilities at an alarming rate.
As Robert Perneczky from the Alzheimer Research Center at Ludwig Maximilians University in Munich states, “We assume that the antibodies work better the earlier they are given in the course of Alzheimer’s disease.” Currently, only patients with mild symptoms are eligible for treatment, as those are the individuals who participated in clinical trials.
Further questions remain about the duration of the drug’s effects and whether they benefit men and women equally, with answers expected in the years to come.
Severe side effects from the therapies are rare. According to Perneczky, “Only through widespread application in the coming years will we be able to better predict which patients will benefit the most from the new antibodies.” The anticipated approval in Europe is, therefore, a significant milestone, especially since the EMA had previously rejected the drugs due to concerns over side effects versus efficacy.
In clinical trials, around 12% of participants experienced minor brain inflammation or bleeding, typically temporary occurrences following the initial injection. Some fatalities have been reported in the USA post-administration, prompting ongoing investigations to determine any potential links to the medications.
Interestingly, emerging reports from the USA and Japan suggest that the occurrence of these adverse brain issues may be lower in clinical practice than in trials, with problems primarily arising in patients with specific genetic variants that are not permitted to receive the antibody in the EU.
To ensure patient safety, regulatory authorities have mandated regular monitoring, requiring those on the new antibody therapies to undergo MRI brain examinations every few weeks.
Currently, the therapy can cost up to $50,000 annually. The complexities of necessary monitoring, combined with the requirement for bi-weekly intravenous administration, currently hinder widespread access to these treatments. Many patients live too far from facilities capable of conducting the required MRI assessments.
Giovanni Frisoni, a neurologist and dementia researcher at the University Hospital Geneva, remains hopeful. “Just like the need for a robust mobile network became evident with the advent of powerful, internet-capable smartphones, we will eventually develop the infrastructure needed for these new treatments,” he explains.
Experts agree that these two antibodies mark just the beginning of a new therapeutic era. There is great anticipation for more effective antibodies and simpler delivery methods, such as subcutaneous injections. Additionally, innovative combination therapies that both clear toxic protein clumps and reduce nerve cell death are under development.
Another source of optimism among dementia researchers is that the long-awaited breakthrough in prevention is now within reach. The effectiveness of the antibodies seems to increase when administered early. Neurobiologist Mathias Jucker notes, “Biologically speaking, there is no reason to restrict these treatments to patients already showing symptoms and brain damage.”
The accumulation of toxic protein clumps occurs over a lifetime, but not everyone who has them will develop dementia. Nerve death typically begins only when sticky fiber bundles form in the nerves, although the trigger for this process remains a mystery.
Jucker proposes a potential future scenario where younger individuals are regularly screened for these protein clumps through newly developed blood tests that can reliably detect their presence. If identified, the antibodies could be administered for a limited period to eliminate the clumps.
The ultimate hope is that this approach could prevent nerve death entirely, thus preventing dementia from developing or at least delaying its onset by decades. Ongoing clinical studies are exploring the preventive efficacy of these antibodies.
Jucker even speculates about the possible culprits behind nerve death: specific proteins linked to chronic inflammation triggered by the protein clumps. “But that remains speculation,” he adds with a knowing smile.