It’s taken longer for Alzheimer’s researchers to discover an anti-amyloid agent against dementia than many experts were predicting 15 years ago, but Bill Klunk, MD, PhD, is optimistic about several drugs in the pipeline. These include aducanumab, an amyloid-targeting antibody now in Phase 3 clinical trials. Klunk, who is Distinguished Professor of Psychiatry and Neurology and Levidow-Pittsburgh Foundation Chair in Alzheimer's Disease and Dementia Disorders, spoke at Brain Day about recent efforts in the field, including potential therapies, that give him hope, even though “we don’t expect these drugs to bring people back to normal,” Klunk said.
Klunk's keynote lecture was one of the highlights of the third annual Brain Day, an all-day event that brings together experts from around Pitt to share their work in neuroscience with not only their colleagues, but with the patient advocacy community. Held on Oct. 26, Brain Day 2017 featured a talk by a local author who has written a book about Alzheimer's disease and research, a panel discussion on Alzheimer’s disease, morning and afternoon poster sessions, and talks by the head of the American Brain Coalition and by a woman who volunteered to undergo brain surgery so that she could operate a robotic arm with her mind.
What makes aducanumab so promising, Klunk says, is that the drug appears to slow down cognitive decline as it clears out abnormal amyloid. While some early trial subjects dropped out due to headache and brain fluid build-up, “our oncology colleagues wouldn’t blink at these side effects,” Klunk said. “No one has ever survived Alzheimer’s disease. They suffer a long and painful course, for them and their families. I think it’s time to be aggressive about it.."
Klunk said he is even more encouraged by current trials of drugs designed to keep sticky protein clumps of amyloid-beta, or a-beta, from accumulating in the first place. Plaques appear in the brain up to 15 years before memory loss is evident, “so an ounce of prevention should be worth even more” than treatment after damage occurs, he said.
Klunk shared the story of Pittsburgh Compound B (PiB), which he co-invented with Pitt radiochemist Chet Mathis, PhD. PiB, used with PET scans, reveals a-beta plaques, which build up in the brain early in Alzheimer’s disease. The imaging advance was hailed worldwide, not only for providing the first method for examining and monitoring the brains of patients with even mild cognitive impairment from Alzheimer’s, but for its potential for assessing whether potential drug therapies reduce or prevent a-beta deposits. The group’s 2004 benchmark paper remains the most frequently cited in the area of Alzheimer’s disease since its publication.
Whether a-beta actually causes Alzheimer’s or is simply a marker for detecting the disease remains somewhat controversial. Klunk falls in the first camp (“amyloid is at least one of the causes of Alzheimer’s disease,” he said), but he advocates research that broadens focus beyond the two usual suspects, a-beta and tau, the protein that shows up as tangles as Alzheimer’s develops.
One final bit of positive news, according to Klunk, is that infusions of federal support for Alzheimer’s research are on target to total more than $1 billion a year, a significant increase over past years. “We’ve been limping along with insufficient funds,” he said. While researchers have estimated that “we need a minimum of $2 billion to mount the critical mass of scientists and diverse ideas to even begin to address a disease as complex as Alzheimer’s,” Klunk said, “it’s encouraging that we may for the first time have the resources to give us half a chance.”
Image at left: Abnormal collections of proteins build up in the brains of Alzheimer's patients. First, cotton ball-like clumps of a-beta appear (shown in brown), followed by tangles of tau (blue).
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