Do you make a lot of lists so you don’t forget stuff? Blank on the name of a colleague you’ve worked with for 20 years? Lose track of what day it is?
We do too, but are cautioned not to panic — that’s normal as we age.
But getting lost driving to a familiar place, or failing to remember the name of that colleague later, or losing track of what season it is, can signal a more serious memory condition: Alzheimer’s.
Alzheimer’s is characterized by abnormal deposits of proteins throughout the brain, impairing the function of once-healthy neurons. It’s the No. 3 cause of death in Orange County and about 84,000 people in O.C. are either living with, or at risk of developing, the condition, according to county statistics and the Alzheimer’s Orange County association.
Nationwide, some 6.2 million people aged 65 and older have Alzheimer’s, and that’s expected to more than double by 2050.
So it’s with some hopeful, enlightened self-interest that we tell you how busy this last week has been for Orange County researchers probing a condition known as “the long goodbye”:
- UC Irvine, a longtime hub of Alzheimer’s investigation, has been awarded a $47 million grant from the National Institute on Aging to support a team developing next-generation mouse models for studying late-onset Alzheimer’s.
- Hoag Hospital’s Pickup Family Neurosciences Institute is seeking participants for a clinical trial of “a promising new investigational treatment” by Acumen Pharmaceuticals that approaches the disease in a new way.
“This grant for UCI is really going to be the power ball that hits it out of the park,” said Jim McAleer, president and CEO of Alzheimer’s Orange County. “It’s bigger than people may think it is on the face of it. It will allow them to lay the groundwork for research, so scientists can count more on what they’re seeing in animal trials as they relate to humans.”
And while the Hoag trial is a Phase 1 study, focused on the new drug’s safety profile, it presents an opportunity for people to get in on the ground floor, so to speak, for later phases on its efficacy. The drug, ACU193, takes a different approach than currently approved medications, seeking to halt the neural toxicity that seems to be at the core of the disease.
“What if it works?” McAleer said. “That would be pretty spectacular. People can be reluctant to raise their hands for Phase 1 trials, but without them, you don’t get anywhere. If it were me, and I were eligible, I would certainly raise my hand and try whatever might work.”
Hoag: New Drug
The drug being tested, ACU193, does not target the infamous amyloid plaques that people who closely follow Alzheimer’s research have heard so much about; the tangles of misfolded proteins that form in the spaces between nerve cells and seem tied to the disease.
Instead, it targets, and binds to, amyloid-beta oligomers, sort of an earlier stage toxin that builds up in the brain.
Oligomers might or might not become plaques, said Dr. Gustavo Alva, psychiatrist at Hoag and principal investigator of the study. But they appear to be quite toxic, and possibly an underlying cause of the neural degeneration that is characteristic of Alzheimer’s.
“The intercept study is exciting because it’s literally a study to intercept the toxic oligomers,” Alva said. “If we can prevent oligomers from binding to these neurons and dendritic spines, we may help preserve function.”
If you think of Alzheimer’s as a long line of dominoes, oligomers may be one of the first few standing in the queue. If you can stop it from toppling, the rest might never fall down.
Hoag is one of 16 sites nationally that will be testing the drug. The only other site in California is slated to be the Orange County Research Institute in Anaheim, which is not yet recruiting, according to clincialtrials.gov.
Interested? Participants should be aged 55 to 90, with mild memory loss or mild dementia. For more information, call 949-764-6797, email clinicalresearch@hoag.org, and read the study outline here: https://bit.ly/3R7bWNR.
UCI: New Money
A thousand brains have been donated to UCI to aid its investigations into Alzheimer’s. And that work will get a big boost from the $47 million coming to UCI from the National Institute on Aging, with the money to be parceled out over five years.
“It’s an incredibly exciting time, and there’s a lot of promise,” said Joshua Grill, director of UCI’s Institute for Memory Impairments and Neurological Disorders.
“We remain in our infancy in our field compared to other fields of medicine, but we’re learning at an incredible rate.”
The university houses one of just two U.S. groups working on late-onset Alzheimer’s mouse models. The research team plans to insert human genetic data into its models to better understand the biology that leads to Alzheimer’s, as well as to set the stage for preclinical drug testing, officials said.
That approach contrasts with previous mouse models that mimic early-onset Alzheimer’s. The project’s next phase will be co-directed by Frank LaFerla, dean of the School of Biological Sciences; Andrea Tenner, a Distinguished Professor of molecular biology and biochemistry; and Kim Green, a professor of neurobiology and behavior.
The project’s highly collaborative nature is a particular point of pride. “This is a robust team that involves three principal investigators and lots of other scientists who all come together to do something huge and important,” Grill said. “We’re very successful, and we’re generating important resources for the work.”
The project began 12 years ago with a $70,000 gift from the Pacific Life Foundation at the urging of Harry Bubb, a former CEO of Pacific Life Insurance Co., and officials said that initial donation illustrates the importance that private philanthropy can play in seeding science. In 2016, the researchers won a $16 million grant from the National Institute on Aging, and this latest grant nearly triples that funding.
But advances are only possible if the community at large joins the effort and participates in the research, Grill said. Folks can register at https://c2c.uci.edu/.
“Truly, because of that of that registry, we have accelerated research in a meaningful way,” he said.
The next decade promises to be one of great progress in fighting Alzheimer’s, the experts said. There most likely will not be one magic bullet for “curing” Alzheimer’s, but multiple therapies that will address brain toxins, and their outfall, in multiple ways.
“Once you hit 50 and 60, you’re staring into the mouth of the lion and the research has a little more immediate impact,” said McAleer of Alzheimer’s Orange County. “If you can stop the first couple of dominos from falling, you’ll chip away at the larger problem.”
