Last month, American pharmaceutical company Eli Lilly ended its fourth study investigating the effectiveness of solanezumab, a potential drug therapy for people with mild cognitive impairment caused by Alzheimer’s disease. Researchers designed the eight-year trial, known as DIAN-TU, to test the therapy’s safety, tolerability, biomarker, and cognitive efficacy on participants with a genetic mutation that causes Alzheimer’s disease. Unfortunately, the trial revealed that solanezumab failed to hinder cognitive decline caused by the neurodegenerative disease or improve disease-related biomarkers (source). The research also failed to garner new support for the popular theory that minimizing levels of amyloid beta, a toxic protein, can delay the progression of Alzheimer’s disease. Nevertheless, the results of DIAN-TU are expected to change the direction of future Alzheimer’s disease studies.
Why Are the Results of the Solanezumab Study Important?
DIAN-TU provides further evidence that dementia in Alzheimer’s disease cannot be halted solely by a treatment that aims to reduce the accumulation of amyloid beta (β) in the brain. In addition to solanezumab, the study also examined gantenerumab, an anti-amyloid-β from Roche, which similarly failed to lessen cognitive decline. Solanezumab and gantenerumab are just two examples of amyloid-blocking drugs that have failed to effectively treat dementia in recent years.
When viewed in combination with previous studies, this trial suggests that Alzheimer’s disease may be a multi-faceted disease that requires a combination therapy of two or more pathological hallmarks like amyloid-β, tau proteins, apolipoprotein B (ApoB100), and neuroinflammation. Depending on the cause of Alzheimer’s disease in each individual patient, treatment may need to be adjusted, much like the search for cures for different cancers. This would imply that Alzheimer’s disease is not a single disease but a group of diseases: “Alzheimer’s spectrum disorder.”
How Is QPS Helping to Find Alternate Pathways using Mouse Models?
To be able to test the efficacy of new compounds in in vitro and in vivo models that properly reflect the multi-faceted Alzheimer’s disease pathology, QPS Austria offers several cell culture and mouse models. Such models include transgenic models expressing different mutated amyloid-β variants, wild type or mutated tau, apolipoprotein E (ApoE), and ApoB100 but also induced models based on tau seeding or the injection of toxins like scopolamine, lipopolysaccharides (LPS), or experimental autoimmune encephalomyelitis (EAE).
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Remember that even negative trial results advance scientific knowledge. Two major studies are still testing the ability of amyloid-blocking drugs to treat cognitive decline in its earliest stages. Future research will likely move in new directions, shifting away from amyloid-blocking treatments and instead viewing Alzheimer’s disease as a spectrum disorder.
Since 1995, QPS has provided discovery, preclinical, and clinical drug development services. An award-winning leader focused on bioanalytics and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction and turnkey laboratories and facilities. For more information, visit www.qps.com or email info@qps.com.
