Could Fixing Brain Energy Reverse Alzheimer’s?
Recent work by Dr. Katrin Andreasson and a large team of scientists has uncovered something intriguing: a molecule called IDO1 may be stealing energy from critical support cells in the brain, and by blocking it, memory and brain function in Alzheimer’s models may be restored.
Here’s the story — and why it matters.
What’s the problem?
In Alzheimer’s disease (AD), two hallmark features dominate headlines: amyloid plaques and tau tangles. These are damaging, yes, but they aren’t the whole story. Even before heavy plaque buildup, there’s evidence that parts of the brain (especially the hippocampus — the memory center) stop metabolizing glucose properly. That means less fuel, which means weaker brain cell activity and memory problems.
In particular, “astrocytes” — star-shaped support cells in the brain — have to convert glucose into lactate, which neurons burn to function. If astrocytes can’t do their job, neurons are nutritionally starved.
Enter IDO1.
This is an enzyme that converts the amino acid tryptophan into kynurenine, part of a pathway that normally helps regulate immune function, among other things. What this new research shows is that in Alzheimer’s, IDO1 becomes overactive in astrocytes. The result? More kynurenine, less glucose metabolism, less lactate, and worse support for neurons.
The PF-068 drug (and what they did in mice):
PF-068 is a highly selective inhibitor of IDO1.
When given to Alzheimer’s-model mice (those engineered to develop amyloid and/or tau), PF-068 restored glucose metabolism in the hippocampus. Astrocytes resumed producing lactate.
Synaptic function improved (the connections between neurons worked better).
Most importantly, the mice performed far better in memory tests: navigating mazes, recognizing objects, etc.
In parallel work, human brain tissues and cells carrying Alzheimer’s pathology also showed elevated kynurenine and metabolic deficits that PF-068 could reverse in vitro.
Why this is exciting:
It suggests a new therapeutic angle: rather than (or in addition to) focusing solely on amyloid or tau, we might treat Alzheimer’s by restoring how the brain generates and uses energy.
PF-068 (or close relatives) are already known from cancer studies. So safety data and pharmacological knowledge already partially exist. That could speed things up if the move toward Alzheimer’s trials is made.
But don’t pop the champagne yet
As promising as it is, there are big questions:
Will the same benefits happen in humans? Mouse brains are simpler in many ways, and Alzheimer’s in people is complicated.
What stage of disease is best for this treatment? Early disease? Mild cognitive impairment? Once the damage is advanced, rescue may be harder.
What about side effects? The kynurenine pathway is involved in immune regulation, among other roles. Suppressing it long-term may risk unwanted effects.
Dosage, brain penetration, and long-term safety in humans remain to be figured out.
Where things stand & what’s next:
Clinically, PF-068 (specifically PF-06840003) has already been tested in humans, but in cancer (glioma) patients, to see if it is safe, and whether it suppresses kynurenine. It was tolerated reasonably well. But that trial was not in Alzheimer’s, and did not measure memory or brain metabolic effects. PubMed
The Alzheimer’s study is recent and preclinical. To move this into Alzheimer’s human trials will require funding, regulatory approval, and likely more animal safety data. If everything goes well, small human trials could start within 1-2 years. But to prove memory rescue in people, to show long-term benefit, will likely take several years.
Bottom line: This work opens a new front in the Alzheimer’s fight — restoring the brain’s fuel supply. If PF-068 or related drugs can safely do in humans what they’ve done in mice, we may have a tool not just to slow Alzheimer’s, but to reverse some of its damage. That’s a big “if,” but also, a welcome hope.