In 1994, a young German neurologist and psychiatrist named Harald Hampel reached a professional crunch point. Should he follow the crowd into researching better-funded, scientifically fashionable neurological conditions such as multiple sclerosis, or follow his calling and strike out on the relatively neglected path of Alzheimer’s disease? “People told me, ‘Don’t do this, you won’t make a career’,” he recalls. He did it anyway.
Today, Hampel’s choice has been vindicated. Once thought to be mysterious and intractable, researchers are learning more about Alzheimer’s disease and believe it is potentially treatable, perhaps even preventable, in the future.
Treatments tailored to target specific aspects of the disease process are in the pipeline, as are blood tests that can detect signs of the disease that can aid early diagnosis and drug development. “We are in a new era where we aim to really understand the complex brain biology behind Alzheimer's disease — not just try to relieve the symptoms,” says Ivan Cheung, US Chairman and Global President of Neurology at Eisai, a Japanese health-care company that has focused on Alzheimer’s disease for the past four decades.
A century of change
These developments are important milestones in the transformation of Alzheimer’s disease from a condition understood mainly in terms of its symptoms to one defined by its biology. Alois Alzheimer, the German neurologist credited with discovering the disease, set the ball rolling in 1906 by describing changes in the brain of Auguste Deter, who had early onset dementia. After Deter died, Alzheimer observed the now-characteristic plaques and tangles in her brain, suggesting this mysterious syndrome had a biological cause. “The dogma at the time was clinical,” says Hampel. “To link it with brain pathology was kind of a revolution.”
Even so, the clinical dogma proved hard to shift. It wasn’t helped by the complexity of the disease, and the difficulty of studying the living brain, which all slowed progress. But in recent years, advances in genetics and molecular biology have sparked another revolution. “All these technological developments, all these scientific studies are now converging into meaningful and effective practical solutions for many patients,” says Hampel.
And a revolution is badly needed. The World Health Organization estimates that 30 million people around the world have Alzheimer’s disease. This number is expected to rise as populations age, with the largest increases in low- and middle-income countries. Globally, by 2030, the economic burden of dementia is expected to reach around $2 trillion, according to the World Alzheimer’s Report 2019.
The personal costs of the disease are also severe. Alzheimer’s inexorably strips a person of their cognitive functions and the memories that make them who they are. Hampel has lived through this: when he was a medical student, his grandmother gradually succumbed to the disease while his family struggled to care for her. “It was a very personal, traumatizing experience,” he says.
His desire to help people with Alzheimer’s disease, combined with his drive to explore unmapped areas in neuroscience, eventually rewarded Hampel with prestigious international academic appointments and drew him to Eisai, a company that shares these values. He is currently Eisai’s Chief Medical Officer, focused on the neurology pipeline — including the Alzheimer’s disease program.
Knowledge is key
Eisai’s scientific purpose is founded on the concept of ‘human health care’ — an understanding that patients and their families are at the center of health care. For Eisai, this means identifying a neglected clinical need and undertaking pioneering research that larger pharmaceutical companies might deem too difficult or risky. “We do not do ‘me too’ research,” says Cheung. “We compete on knowledge, where we believe we can do something great.”
It has been a hard road, yet Eisai is at the forefront of research and development for Alzheimer’s disease, from symptomatic breakthrough treatment in the 1980s and 1990s to its current focus on developing antibodies to tackle the underlying disease processes.
Changes in brain cells begin decades before the clinical signs of Alzheimer's disease. One of the earliest is the appearance of protein clumps, or ‘plaques’, between neurons, which are composed of fragments of a protein called beta-amyloid. Meanwhile, within the neurons, aggregates of tau protein, called neurofibrillary tangles, form. Amyloid plaques and tau tangles are associated with inflammation, disrupted communication between neurons, and cell death.
“We've made enormous gains,” says Jeffrey Cummings, a neurologist specializing in Alzheimer’s disease at the University of Nevada, and a consultant for Eisai. “We understand there's a role for amyloid and tau, maybe inflammation. We know much more than we did just a few years ago — but we need to know more.” Nevertheless, these gains have already delivered benefits, he adds.
A key benefit is the discovery of ‘biomarkers’ — molecules that give clues about the underlying disease process. One of the problems neurologists were facing was trying to accurately diagnose Alzheimer’s disease, given that they were unable to look inside patients’ brains for the plaques and tangles. “Biomarkers allow us to understand, from the outside, what is happening on the inside,” says Cummings.
In the past two decades, scientists have developed imaging techniques that can detect amyloid plaques in living patients; they also found signatures of the plaques and tangles in the fluid that surrounds the brain and spinal cord. But the real game-changer would be to find biomarkers in the blood. Blood-based biomarkers make ‘liquid biopsies’ possible, enabling neurologists to track a patient’s disease progression across time. “We’re making tremendous progress with blood-based biomarkers, and that will be a transformative gain,” says Cummings.
So good has been progress, that several scientists have proposed using biomarkers, rather than symptoms, to classify Alzheimer’s disease. Ultimately, Eisai would like to develop a routine screening test based on blood biomarkers that people could easily access in a physician’s office, to catch the disease in its earliest, asymptomatic stages, when intervention might be possible, says Cheung.
That might sound ambitious, but until recently so was the idea that scientists could see into the living brain or be able to build a holistic picture of a patient’s disease and track it over time, says Hampel. And it would make a fitting conclusion to a revolution begun by Dr. Alois Alzheimer more than a century ago.
To learn more about Eisai’s approach to Alzheimer’s disease and other neurological conditions, please visit https://us.eisai.com/our-science/disease-areas/neurology.
