Doug Williamson says brain research is a bit like a hack-a-thon, albeit one with profound stakes. As Chief Medical Officer and Vice President of U.S. Medical at Lundbeck—a global pharmaceutical company focused on brain diseases—Williamson works with a team of scientists who spend their days probing for flaws in the world’s most-firewalled system: the brain.
“Studying the brain is like trying to decipher highly complex code, all while a virus is lurking, waiting to corrupt your data,” says Williamson, whose company searches for new treatments for complex brain disorders like Alzheimer’s disease, which affects about 5.5 million people in the United States and is the sixth-leading cause of death nationwide. “Even more challenging is that you can’t predict when the virus will strike or what sequence of events will trigger it.”
Every organ in the body has its own beauty and complexity, but the brain—which coordinates all the other organs—is particularly complex, adds Williamson. “The brain houses our personalities, thoughts, and identities,” he says, “which can be easy to take for granted until it all breaks down.”
While blood samples and biopsies can somewhat illuminate understanding of disease, the intricacies of the brain make studying the chemistry, mapping the components, deciphering how neural pathways function, and detecting abnormalities in living patients highly challenging. And that makes the pursuit of therapies to treat brain diseases especially difficult.
One major hurdle for neuroscientists seeking to develop new treatments is recruiting participants for clinical trials. Because brain disorders like Alzheimer’s can be difficult to diagnose in early stages, access to people in the very-early or pre-symptomatic stages of the disease could provide insights into the disease development and progression. And that could lead to new medicines that could even slow or prevent the onset of the memory-robbing disorder.
Collectively, explains Williamson, the research obstacles have left the brain and, by extension, Alzheimer’s disease, an outlier in medical progress. While treatment breakthroughs have transformed other serious diseases, such as HIV and certain cancers, from death sentences to chronic, manageable conditions, Alzheimer’s still cannot be conclusively prevented, cured, or even slowed despite billions of dollars being invested in research. Between 1998 and 2017, just four new treatments for Alzheimer’s appeared on the U.S. market, while an additional 146 attempts ended in failure.
The high failure rate, Williamson explains, is due to the fact that scientists have yet to uncover precisely what causes the disease, despite ongoing research since Alzheimer’s was first discovered in 1906. The dominant theory, he says, suggests that abnormal protein deposits form in the brain, choking off neuron activity and shrinking brain tissue. However, neuroscientists haven’t determined conclusively why these deposits start forming in the first place, or exactly what role the deposits play in the cell death that leads to Alzheimer’s memory and cognition symptoms.
“For decades we’ve been hard at work to understand these diseases and develop better treatments, but a truly novel breakthrough has continued to evade us,” says Williamson, noting that, without a new treatment, Alzheimer’s experts predict the number of Americans with the disease could more than double by 2050, resulting in more than $1 trillion in direct Alzheimer’s-related medical costs.
That’s not to say the efforts of neuroscientists and academic and pharmaceutical researchers have been in vain. In recent years, the rallying cry of the Alzheimer’s community has been “setbacks not failures”—an understanding, Williamson explains, that each experiment, successful or not, reveals a new lesson. Despite the absence of a breakthrough, he says, researchers are inching closer to cracking the code.
For example, in recent years, scientists have uncovered biomarkers of Alzheimer’s pathology that aid diagnosis and earlier treatment. Researchers also are investigating the link between Alzheimer’s and inflammation, and they are exploring how managing neuroinflammation could prevent or minimize Alzheimer’s symptoms. They also have developed a better understanding of the genetic and lifestyle factors that can increase an individual’s risk of Alzheimer’s, knowledge that could prove valuable in developing highly targeted, early interventions.
“For every Alzheimer’s study that doesn’t work out, or every new Alzheimer’s drug that doesn’t meet its end points, we learn something that moves us forward,” says Williamson, adding that more than 90 medicines for the treatment of Alzheimer’s and other dementias are currently in clinical development. “I have no doubt that soon, this understanding will lead to a discovery that will change the lives of patients for good.”
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