The Alzheimer's research revolution
There’s a revolution underway in the Alzheimer’s research world. At the heart is a change in the way researchers and regulators define and stage the disease, and it might just lead to the breakthrough Alzheimer’s researchers, patients and families have been waiting for.
With researchers from around the world gathering in Chicago this week for the Alzheimer’s Association International Conference (AAIC), it’s a good time to examine what’s changing, how it will reshape the Alzheimer’s research landscape and the key role Lundbeck is playing in this revolution.
Honing in on biomarkers
Alzheimer’s is a complex disease that is associated with many molecular, cellular and physiological changes in the brain. Some of these can begin decades before symptoms appear, which is why focusing on Alzheimer’s biomarkers is so important. In the same way that diabetes biomarkers help clinicians diagnose and treat pre-diabetes before symptoms appear, targeting Alzheimer’s biomarkers could one day help clinicians treat Alzheimer’s in its earliest stages, dramatically limiting the impact of this devastating disease.
Thanks to advances in biotechnology and increased knowledge of the disease, we now have greater understanding of Alzheimer’s biomarkers. As of today, there are three sets of biomarkers linked to Alzheimer’s pathologies:
1. Abnormal levels of the protein beta-amyloid, as seen in PET scan or cerebrospinal fluid (CSF) sample.
2. Elevated levels of the protein tau, as seen in PET scan or CSF.
3. Neurodegeneration/neuronal injury, as seen in CSF, PET scan or MRI.
Focusing on these biomarkers—independent from any cognitive or behavioral symptoms—can help researchers diagnose the disease earlier and track treatment progression. Significantly, it also can help researchers qualify clinical trial participants with much greater precision, and that could lead to more successful trials. In the past, up to 30 percent of Alzheimer’s trial participants did not even have the Alzheimer’s-related brain change targeted by the experimental drug.
Defining Alzheimer’s based on biomarkers represents both a shift in thinking about the disease and an important advance in our fight against it.
A new biological definition
Biomarker-focused research got a major boost in April when the National Institute on Aging and the Alzheimer’s Association (NIA-AA) issued a new research “framework.” The framework encourages researchers to focus less on symptoms and sets forth a new biological definition of the disease. As a member of the Alzheimer’s Association Research Roundtable, I had the opportunity to review and provide comment on the framework prior to publication and think this new definition represents an important step forward in Alzheimer’s research.
According to the new framework:
- Anyone with the beta amyloid biomarker is considered to have an Alzheimer’s pathological change.
- Anyone with the beta amyloid biomarker and tau biomarker is classified as Alzheimer’s disease.
- Neurodegeneration on its own is not enough to identify someone as having Alzheimer’s.
- Neurodegeneration with beta amyloid biomarker is considered Alzheimer’s pathological change, and neurodegeneration with both beta amyloid and tau biomarkers is classified as Alzheimer’s disease.
The framework also established six stages of Alzheimer’s that are based on severity of clinical symptoms. These symptomatic stages range from biomarker with no symptoms, to biomarker and severe dementia.
Using the new biological definition and staging system will help researchers categorize trial participants and target investigational therapies more accurately. Defining Alzheimer’s based on biomarkers represents both a shift in thinking about the disease and an important advance in our fight against it.
Regulatory recognition
The Food and Drug Administration (FDA) also is encouraging focus on biomarkers and recently issued updated guidance for Alzheimer’s drug development. In the past, the clinical criteria for enrollment in Alzheimer’s clinical trials was based on symptoms—specifically, symptoms that are typically found in people with later stages of disease. Now, researchers can include pre-symptomatic patients in Alzheimer’s trials.
Also, the FDA revised the endpoints used to measure the success of Alzheimer’s trials. Previously, drug makers had to prove that new treatments improved patients’ cognition and function. But patients with early-stage disease may not yet have challenges with daily functioning, and so a trial targeting early-stage disease would have a difficult time demonstrating improved functioning. This updated guidance will, hopefully, encourage more early-stage trials.
Lundbeck’s role in the revolution
At Lundbeck, we are already working to develop disease-modifying therapies that correlate to biomarkers. For example, we are investigating a tau antibody therapy that could stop the spreading of tau tangles. We also have an active phase 1 trial for an immunotherapy that targets and destroys beta-amyloid plaque.
We also are working to expand the field’s understanding of biomarkers through a variety of partnerships. For example, we support the Alzheimer’s Disease Neuroimaging Initiative and the European Prevention of Alzheimer’s Dementia Consortium. And with U.S. biotech company Cerveau, we are developing a scanning tool that will help researchers visualise tau tangles in patients’ brains.
As the only global pharmaceutical company solely focused on brain disorders, we support efforts that advance research and point us closer to a day when people will not suffer from this devastating disease. And we welcome and champion the current research revolution.
