As the sun continues to set on the Baby Boomer generation, a looming crisis is emerging: the scourge of late-stage dementia.
Anyone who’s struggled to cope with Alzheimer’s or a similar degenerative syndrome as it decimates the cognitive and eventually the physical functioning of a loved one knows how relentlessly the condition progresses, and how helpless we are to deal with it.
Until recently, medical researchers have fared no better.
As a recent article in The Scientist explained, the success rate of investigational drugs developed to treat Alzheimer’s disease is abysmal — less than 10% of such drugs show any effectiveness, and that’s not good news for the estimated 5.4 million Americans suffering from dementia.
“The scientific community has watched in dismay, time and again, as potential Alzheimer’s drugs that produced promising data in rodent models failed to work as expected in humans,” Edward G. Barrett, senior scientist and senior director of translational sciences-pharmacology at the nonprofit Lovelace Biomedical, wrote. “So far, no drug candidates targeting the beta-amyloid pathway have prevailed through late-stage clinical trials,” he stated, noting that both Merck and Eli Lilly recently halted trials when drugs that targeted the amyloid plaques thought to be responsible for disrupting neurological function proved to be ineffective.
Where does that leave researchers? As Barrett asked, “Are there other approaches we could be taking that could give us valuable insight before investing in human studies?”
The answer is one that animal activists don’t want to hear, but for anyone who’s been a caregiver for someone suffering from Alzheimer’s it’s the only one that makes sense.
Of mice and men
As Barrett noted, laboratory mice are a useful modality to obtain preclinical proof of efficacy, as the FDA phrases it, for a new drug before it’s approved for human clinical trials. It’s relatively quick and cost-effective method of determining if a drug is acting on the correct biological targets.
Only one problem: Mice don’t develop Alzheimer’s, and they don’t naturally accumulate the amyloid proteins responsible for the pathology. Even mice that are genetically altered to develop the amyloid proteins are “incomplete representations of the disease pathology,” according to Barrett.
“That could explain the disconnect between what we’re seeing in the laboratory and what’s happening in the clinical setting,” he wrote.”
In other words, why promising drugs that seem effective in mice don’t seem to work in people.
The solution? Man’s best friend.
“Dogs match quite well with humans in terms of underlying disease development and response to therapy,” he wrote. “Unlike mice, dogs naturally develop beta-amyloid plaques … and show associated cognitive decline as they age. This is a unique quality of dogs; even nonhuman primates do not exhibit this combination.
“Could drug companies minimize their risk of expensive clinical trial failures by transitioning to canines for definitive preclinical studies? Based on two decades of preclinical work with dogs, I believe the answer is yes.”
I can hear the wailing from animal rights activists: “NO-O-O-O!!!”
We can’t subject poor, innocent dogs to “definitive preclinical studies,” whatever those are. Just come up with some computer program that will do the same thing!
Unfortunately, that’s not going to happen — not in this lifetime.
If some techno-geek could develop a program that mimics the human biological system with such precision that researchers could plug in data and output a drug that would earn billions for some pharmaceutical firm, don’t you think that would have already happened?
Like last century?
Barrett, on the other hand, conducted a 20-month longitudinal study involving 34 11- to 12-year-old beagles. He and his collaborators used an immunotherapy vaccine to remove the beta-amyloid plaques in older dogs, but they discovered the drug therapy alone didn’t prevent cognitive decline or restore cognitive functioning.
When they added “behavioral enrichment” to the drug treatment, however, the research team found that the combination of drug therapy and behavioral enrichment led to cognitive improvement in the dogs, although there were benefits to memory.
(Not sure how that works. What, the dog forgets how to sit, beg and roll over? Several of the dogs I’ve had over the years routinely “forgot” those tricks — unless there was a tasty treat at hand.)
“With the combination treatment, we even saw benefits in animals with existing plaques and cognitive dysfunction,” Barrett wrote, “which is promising for patients with mild-to-moderate Alzheimer’s disease. The fact that dogs more closely model human disease and cognitive decline is priceless — especially for … Alzheimer’s, in which age is a central component of the condition.”
That said, Barrett acknowledged that the solution isn’t black and white. Dogs can’t totally replace rodent models for research on neurocognitive disorders, he cautioned. It’s too expensive, and the dogs have to be older animals prone to developing a degenerative disorder that mimics Alzheimer’s.
But canine models could “supplement preclinical work,” improving the chances that a promising drug will successfully translate to human clinical practice.
If it even delivers incremental progress, I’ll take supplementation over software any day of the week.
The opinions in this commentary are those of Dan Murphy, veteran journalist and commentator