Alzheimer’s disease research and drug development is evolving at a rapid pace. Decades of research has led to the approval of the first disease-modifying drugs and new pathological discoveries. The first blood-based biomarker tests will bring equitable access to screening and diagnosis while accelerating clinical research. These major breakthroughs in the last few years alone represent a pivotal time in the Alzheimer’s disease landscape.
“This is an unprecedented time for Alzheimer’s research. Significant advances have been made in understanding pathological factors affecting disease, long-awaited disease-modifying treatments have been approved and more convenient diagnostic tools are becoming available - all major steps in changing the course and impact of this once-elusive disease,” stated Dr. David Morgan, Director of the Alzheimer’s Alliance and Professor of Translational Neuroscience at Michigan State University.
A new era of Alzheimer’s disease therapies
There are now ten treatments approved for Alzheimer’s disease, including two recently-approved disease-modifying drugs – the most recent approved in July 2024. The disease-modifying treatments are a class of monoclonal antibodies that target the removal of amyloid-beta plaque build-up in those with mild cognitive impairment or early Alzheimer’s disease.
Researchers convening at the recent Alzheimer’s Association International Conference acknowledged that the community can build upon the latest advances. “We need new therapies, many more targets, better drugs, more convenient drugs, but it is important that we have changed the landscape by having disease-modifying therapies.”
Next wave of Alzheimer’s disease testing - plasma-based biomarker tests
One of the major advances in the Alzheimer’s disease landscape is the emerging blood-based biomarkers tests that are expected to improve diagnosis in primary care, reduce wait times for treatment initiation, accelerate clinical trial recruitment and greatly lower the cost of diagnosing Alzheimer’s.
Only 10 years ago, Alzheimer’s disease diagnosis relied on symptom observations. Since then, the gold standard has moved to a PET scan or lumbar puncture. These diagnostic options are costly, invasive and inaccessible in many communities.
One of the challenges to accessing the new monoclonal antibody treatments is the availability of PET scans to screen for qualified patients. The convenience of blood-based biomarker tests would relieve this bottleneck.
A panel has been assigned by the Alzheimer’s Association to conduct a systematic review of the plasma-based biomarker tests and expects to provide a clinical practice guideline in early to mid 2025.
Emerging biological pathways as drug development targets
Most of the recent drug development efforts have been focused on mechanisms that aim to remove amyloid plaque build-up or tau tangles, main hallmarks of the disease.
Researchers are now turning their attention to the role of inflammation in Alzheimer’s disease development and progression. Most recently, a study of a GLP-1 agonist, part of a class of drugs used for diabetes, weight loss and heart disease, demonstrated neuroprotective effects that may help to protect the brains of people with Alzheimer’s disease. Previous studies have shown how GLP-1 agonists can reduce neuroinflammation. The GLP-1 agonists did not alter amyloid-β and tau biomarkers nor show improvements in cognition, but the anti-inflammatory and neuroprotective effects of GLP-1 agonists warrant further studies and opens new biological pathways in the potential treatment of Alzheimer’s.
The study showed the potential of repurposing diabetes drugs in the treatment of Alzheimer’s and exploring drug candidates that target similar biological pathways to diabetes treatments.
Identifying a combination of therapies or a multi-factorial Approach
To treat a complex disease such as Alzheimer’s will likely require a combination of therapies or a multi-factorial approach. The Alzheimer’s Association has identified modifiable risk factors associated with the development and progression of Alzheimer’s disease including untreated visual loss, LDL cholesterol, hearing loss, depression, Type 2 diabetes, exercise and cognitive stimulation. While these preventative lifestyle measures may delay the onset and progression of Alzheimer’s disease, lifestyle habits alone are unlikely to prevent disease development.
Clinicians believe that a multi-factorial approach will be required that includes lifestyle habits and a combination of disease-modifying and symptomatic treatments that target multiple biological pathways.
InMed’s INM-901 demonstrates a novel, multi-factorial approach to treating Alzheimer’s
Among the drug candidates in preclinical development is InMed’s INM-901, a promising small molecule that has demonstrated disease-modifying effects and appears to target multiple biological pathways, including the peroxisome proliferator-activated receptor (PPAR), which is associated with diabetes development and plays an important role in cell metabolism and immune response.
Preclinical studies of INM-901 in well-characterized Alzheimer’s disease models indicate that INM-901 reduces neuroinflammation and cell death and promotes the growth of neurites in the brain – which enables cell-to-cell communication and is essential for brain processing. The growth of neurites, which is diminished in patients with Alzheimer’s, signifies enhanced neuronal function and may indicate the potential to restore the damage caused by Alzheimer’s disease.
InMed’s INM-901 is among the several promising treatments in development that may be able to change the course of Alzheimer’s disease.