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Boomer Health: Alzheimer’s expert to present latest findings at the Norton

Palm Beach Post - 11/14/2021

During November's National Alzheimer's Awareness Month, there will be no shortage of news about the latest research and potential treatments.

There will also be plenty of discussion about the controversy surrounding the drug Aduhelm (generically known as Aducanumab), which earlier this year the FDA granted "accelerated" approval as the only drug on the market to treat Alzheimer's.

Critics of the drug, and the FDA, don't believe that the drug's manufacturer has shown enough clinical trial evidence that Aduhelm is effective in slowing the progression of Alzheimer's in its early stages. There are also grave concerns about the drug's potential side effects as well as its prohibitive cost.

Conversely, Aduhelm's advocates — most of whom are either affiliated in some way with the manufacturer or are regular folks battling the disease and looking for some kind of hope — argue that the FDA's approval might spur other manufacturers to increase their efforts to develop other more effective medications.

For the layperson — especially one who has a loved one suffering from this debilitating and invariably fatal disease — the drug controversy, and other Alzheimer's-related issues, can be difficult to make sense of.

Fortunately for South Floridians, there's a new series of Alzheimer's-related presentations coming to the Norton Museum of Art and featuring the world's leading experts in Alzheimer's disease research and potential treatments.

At these events, attendees will be able to engage with experts, ask questions and learn about what's happening now and what's on the near horizon.

Called Tomorrow's Breakthroughs Today, the three-symposium series kicks off at 4:30 p.m. Wednesday. The other two symposiums are scheduled for 4:30 p.m.Jan. 31 and April 26.

The first presentation will feature researcher Roberta Diaz Brinton, director of the University of Arizona Health Sciences' UA Center for Innovation in Brain Science.

Brinton has been studying the brain — and how Alzheimer's affects it — for nearly four decades. She's especially interested in how the disease manifests in women as they go through the hormonal changes associated with menopause.

"During research in our lab, we have demonstrated that ovarian steroids and neurosteroids are key mechanistic regulators of the bioenergetic and regenerative systems of the brain," she said. "Moreover, loss of ovarian hormones leads to activation of a sequence of compensatory responses that ultimately lead to development of Alzheimer's pathology."

According to the Alzheimer's Association, of the estimated 6 million Alzheimer's sufferers in the U.S., some two-thirds are women.

Brinton and her team believe they've made three "fundamental" discoveries about the aging female brain's vulnerability to developing Alzheimer's:

Transitioning into menopause is an energetic and neurological transition for the brain that leads to the brain having a decrease in glucose metabolism. Because glucose is the primary fuel to generate "energy" — that is, the mitochondrial enzyme ATP — in the brain, even modest declines in glucose metabolism can lead to decline in synaptic and cognitive function.

Estrogen regulates the entire bioenergetic system of the brain, from glucose uptake into the brain to glucose metabolism and to mitochondrial ATP production.

The loss of estrogenic control of glucose-derived ATP leads to brain utilization of an alternative fuel, ketone bodies. Use of ketone bodies by the brain is akin to "starvation" of the brain and of type 2 diabetes. "While this adaptation is advantageous in the short run, it can be disastrous in the long run," noted Brinton.

Brinton believes that, while most Alzheimer's diagnoses are made in the middle and late stages of the disease "we know Alzheimer's disease can start 10 to 20 years before diagnosis. Further, we know that there is a sex difference in the prevalence of the disease. Curing the disease requires that we discover the earliest events in the brain in both women and men that lead to emergence of disease symptoms later in life," she said in a 2019 interview that appears on the University of Arizona's website.

In 2017, Brinton was awarded by the Alzheimer's Drug Discovery Foundation a $150,000 grant — the annual Melvin R. Goodes Prize — to develop a therapeutic use of allopregnanolone, a neuro-steroid that activates neural stem cells to generate new brain cells. This led to her later being awarded a $5.9 million grant by the National Institute on Aging (part of the National Institutes of Health) to conduct clinical trials on the drug, as well as try to develop other preventive medications.

(Incidentally, the other Tomorrow's Breakthroughs Today presenters — Dr. Frank Longo, professor and chair of the Department of Neurology and Neurological Sciences at Stanford University and the founder of PharmatrophiX; and Dr. Jeffrey Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada — are also former Goodes Prize recipients.)

"Outcomes of our research will generate therapeutic targets for precision medicine interventions for both women and men during the early stage of Alzheimer's, when the potential to prevent, delay and reverse disease progression is greatest," said Brinton.

Her ultimate goal is to create an array of disparate Alzheimer's treatment protocols.

She said she and her team are working "to develop therapeutics that promote the health of the nervous system and move away from the one-size-fits-all model. Our precision therapeutic approach will generate the right therapeutics at the right time. The idea that one therapy works for all people, all the time, has not worked and is unlikely to work. We need a portfolio of treatments that can be deployed to combat the disease based on gender, genotype and stage of the disease."

The Tomorrow's Breakthroughs Today symposiums are the brainchild of Palm Beach residents Heidi and Tom McWilliams, both of whom are benefactors of, and directly involved with, the Alzheimer's Drug Discovery Foundation. Tom McWilliams currently serves as co-vice chairman and treasurer of the organization; Heidi McWilliams is a co-chairwoman of the organization's Fifth Annual Hope on the Horizon Dinner scheduled for March 3 at the Beach Club in Palm Beach.

What: Tomorrow's Breakthroughs Today symposiums on Alzheimer's research and potential treatments

When: 4:30 p.m. Wednesday, Jan. 31 and April 26

Where: Norton Museum of Art, 1450 S. Dixie Highway, West Palm Beach

Cost: Single tickets are $100; a package for all three is $250

Contact: For more information, visit alzdiscovery.org/events

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