TINY BEASTS

Are Microbes Stealing Your Mind?

Could bacteria hold the answer to an Alzheimer’s cure? Some researchers say yes.

08.09.15 2:00 AM ET

Time moves in one direction, memory in another.
  — William Gibson

One great frustration of longer-living humans is that millions of us will one day lose our minds. Our essence will whither away, causing the rest of us to ponder just how substantial the trove of our memories and experiences really are.

This existential threat is terrifying since, despite armies of brilliant researchers and billions of dollars, there is no cure for Alzheimer’s disease and the many other forms of neuro-degeneration. Nor are the underlying causes well understood, beyond the primary risk factor of aging, and in some cases the role of errant genes.

Now comes a possible culprit that falls outside of mainstream research, though researchers have discussed it for decades: bacteria. Yes, those tiny single-cell beasties that infest nearly every nook and cranny of our bodies. Along with this bacteria-causes-dementia theory comes a possible treatment or cure for Alzheimer’s that is also as unorthodox as it is as yet unproven: antibiotics.

The latest dementia-microbe proposition comes from University of California at San Francisco psychiatrist Steve Dominy. He studies neurocognitive disorders in HIV-positive patients, including the contribution of proteins from the gut that pass through the blood-brain barrier and may affect the neural health of AIDS patients.

From this work Dominy has detected what he believes is a link between a specific bacteria and some forms of dementia. Last year, he co-founded Cortexyme, which has raised $2.5 million to investigate his idea, one of the first ever companies in what might be termed the “bacterial neuro-degeneration” space.

This comes as scientists are realizing that these micro-critters are far more important influencers in our health and in a broad range of disease and wellness factors than previously assumed.

Right now 100 trillion bacteria are swarming, chewing, spitting out chemicals, and infesting your gut, liver, and brain, and the tip of your tongue. Bacteria outnumber human cells 10 to 1, although they are so small that they collectively comprise a mere 1-3 percent of your body mass.

They influence everything from the digestion of food to Crohn’s disease, a chronic, often debilitating inflammation of the bowels that seems to be influenced by too little “good” bacteria and too many “bad” bacteria in the gut. Scientists are delving into how microbes affect heart disease, diabetes, cancer—and the immune systems of newborns.

In June the New York Times Magazine ran a story titled: “Can the bacteria in your gut explain your mood?”, which reported on new evidence that microbes in our stomachs can secrete neurochemicals like dopamine that correlate with depression and anxiety, and can impact other aspects of mood.

The same magazine ran a story last year about the unexpected role of “good” bacteria on keeping our skin healthy—microbes that people wash off, but maybe shouldn’t.

In recent years the National Institutes of Health and other research organizations have spent tens of millions of dollars on projects like the NIH’s Human Microbiome Project to investigate the role of microbes in disease that scientists previously thought were unconnected to our little companions. (Much more is needed, however, than the $140 million-plus spent by the NIH since 2007 on the HMP).

The private sector is also laying out tens of millions of dollars to study and develop products using microbes. One company, Second Genome, has raised $19 million to develop drugs using chemicals secreted by bugs in our guts. Another company, U-Biome, is selling kits that anyone can use to run experiments on their own or other’s on-board bacteria.

A sea change in bacteria’s role in disease came in 1982 when Australian physician and researcher Barry Marshall and pathologist Robin Warren discovered that a common bacteria found in humans, H. pylori, could be found in and were probably the cause of ulcers.

The denizens of mainstream medicine at the time claimed this was bunk, insisting that ulcers were caused by stress and spicy foods. In 1984 a frustrated Marshall downed a petri dish of H. pylori to prove his claim, and sure enough contracted ulcers. In 2005, he and Warren were awarded the Nobel Prize, and antibiotics are now a standard of care for ulcers.

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Casey Lynch, the co-founder and CEO of Cortexyme, said in a recent Arc talk in San Francisco that a similar story might be played out with bacteria and Alzheimer’s with Steve Dominy’s discovery. (Click here to watch Casey Lynch’s Arc Fusion Talk delivered in San Francisco, courtesy of Arc Programs.)

Right now, Lynch explained, the conventional approach to vanquishing Alzheimer’s disease centers on the buildup of amyloid beta peptides and other structures that cause inflammation in the brain.

“A-beta has been the focus of billions and billions of dollars and a huge amount of research,” said Lynch, who also has worked as a neuroscientist and is the founder of NeuroInsights, a consulting firm for the neurotech industry. “Really 95 percent of the money has gone into this target but most of the studies are failing, so I was excited about a novel approach.” She continued:

“So we set out to do a number of experiments to prove to ourselves, and the rest of the community, that this was indeed a credible theory and that we could develop treatments targeting it. The first thing we did was look at as many human brains as we could get our hands on. So far we’ve looked at 43 Alzheimer’s patients, and every single one of them has this bacterial protease [enzymes that breaks down proteins] in their brain.

“In healthy people some are clean but some do have small levels of this bacteria and its proteases. So we think that those people are on a path either to Alzheimer’s or maybe accelerated aging. We don’t know yet.”

Based in South San Francisco, Cortexyme has been funded by angel investors, as well as Dolby Family Ventures and Breakout Labs. They are working on raising another $15 million, with an undisclosed Pharma likely to take the lead.

Researchers have been proposing that bacteria may influence dementia and Alzheimer’s for decades, although this notion remains on the outer edge of conventional research. “Little is actually known about the brain microbiome,” said Lynch.

Another UCSF physician and researcher, Michel Weiner, said he was not aware of other researchers or companies working on the bacterial idea for Alzheimer’s, although he believes that the idea may have merit. Another prominent Alzheimer’s researcher, Rudy Tanzi of Harvard, said that his lab has been working for years on understanding the role of bacteria in Alzheimer’s and other neuro-diseases of aging.

Cortexyme is mum on details about their bug. “We are not disclosing the bacteria yet,” said Lynch, although she suggested that their rogue microbe increases the levels of A-beta in the brain. 

The company hopes to develop a method for disrupting or shutting down the ill effects of their mystery bacteria, which Lynch said is resistant to classic antibiotics. The company hopes to develop next-generation antibiotics known as “narrow spectrum antibiotics” that would protect the neurons from Dominy’s bacteria while disabling it but not blowing it up, which could release toxins in the brain. 

We are at the very beginning of understanding what the critters inside us are doing—including those in our brains that almost certainly impact our minds, and therefore who we are. Clearly, much more work remains. This line of attack against dementia could also fail. Yet it is intriguing to consider what would happen if Alzheimer’s goes the way of ulcers, which are now easily treated.

One wonders: What would we do with all of those abruptly clear minds among our senior citizens?