When we blocked its expression in mice, we were able to slow down the disease.
In laboratories at Oregon Health & Science University, scientists have found a molecular key that may help slow one of medicine's most merciless diseases. By identifying a protein called alpha-5 integrin as a driver of ALS progression in immune cells, and demonstrating that an already-approved cancer antibody can quiet its influence in mice, researchers have opened a door that was not previously known to exist. The discovery belongs to a longer human story of learning to turn the immune system from adversary to ally — a story that has already rewritten cancer treatment and is now reaching toward the mind and nervous system.
- ALS remains a fatal sentence for those diagnosed, with no cure and only one modestly effective drug standing between patients and the disease's relentless advance.
- A high-throughput screening effort uncovered alpha-5 integrin concentrated precisely where ALS inflicts its worst damage — the motor cortex, spinal cord, and peripheral nerves — in tissue from 139 donated human brains.
- When researchers blocked the protein in genetically predisposed mice, the animals moved better, declined more slowly, and lived longer — results the team described as almost unbelievable.
- Because the monoclonal antibody targeting alpha-5 integrin already carries FDA approval for cancer, the usual years-long safety gauntlet could be bypassed, compressing the timeline toward human trials.
- Dose-response studies in mice are the immediate next step, and if they hold, ALS patients — for whom time is measured in months — may see a new immunotherapy approach reach clinical testing sooner than conventional drug development would allow.
At Oregon Health & Science University, a research team has identified a protein on immune cells that appears to accelerate ALS, and shown that blocking it with an existing drug slows the disease in mice — the first evidence that modulating immune cells can meaningfully alter the course of amyotrophic lateral sclerosis.
The protein, alpha-5 integrin, was discovered through high-throughput screening to be expressed at elevated levels on microglial cells and macrophages in the brains and spinal cords of ALS patients. To validate the finding, researchers examined postmortem tissue from 139 donated brains and found the protein concentrated in the motor cortex, spinal cord, and peripheral nerves — the precise regions the disease destroys. Crucially, a monoclonal antibody targeting alpha-5 integrin had already been developed and FDA-approved for certain cancers.
When the team tested the antibody in mice genetically predisposed to ALS, the results were striking. Treated animals maintained motor function longer, experienced slower disease progression, and outlived untreated counterparts. "We couldn't believe they were doing so much better," said senior author Bahareh Ajami. Because the antibody has already cleared extensive safety testing, it could be repurposed for ALS far more quickly than a drug built from scratch — a critical advantage when patients measure their remaining time in months.
Ajami situated the work within a broader transformation in how scientists approach neurodegeneration. Immunotherapy has already reshaped cancer treatment and is now showing promise in Alzheimer's disease; her findings suggest ALS may be similarly vulnerable to immune-targeted intervention. She was careful, however, to temper expectations: "At this point, we cannot say it's a cure but it's a very interesting start."
Next steps involve dose-response studies in mice to establish optimal treatment levels. If those succeed, the path to human trials could move with unusual speed. For patients living with a disease that currently offers no cure, even a therapy that slows rather than stops progression would mark a meaningful turn in a long and difficult story.
Researchers at Oregon Health & Science University have identified a protein on immune cells that appears to drive the progression of ALS, and they've found that blocking it with an existing drug slows the disease in mice. The work, published in the Proceedings of the National Academy of Sciences, represents the first time scientists have shown that modulating immune cells can meaningfully slow amyotrophic lateral sclerosis, a fatal neurodegenerative condition that gradually paralyzes its victims by destroying the motor neurons that control movement.
The protein in question is called alpha-5 integrin. Using a high-throughput screening technique, the team discovered it is expressed at high levels on microglial cells and macrophages—immune cells in the brain and spinal cord—in people with ALS. To confirm this finding, researchers examined postmortem tissue from 139 donated brains and found alpha-5 integrin concentrated in the motor cortex, spinal cord, and peripheral nerves, exactly where ALS does its damage. The discovery pointed toward a potential treatment: a monoclonal antibody that targets this protein had already been developed and approved by the FDA for treating certain cancers. "When we blocked its expression in mice, we were able to slow down the disease," said Bahareh Ajami, the study's senior author and an assistant professor at OHSU's School of Medicine.
The team tested the antibody in mice genetically predisposed to develop ALS. The results were striking. The treated mice maintained their motor function longer, experienced delayed disease progression, and lived longer than untreated animals. "We couldn't believe they were doing so much better," Ajami recalled. Because the antibody has already undergone extensive safety testing for cancer treatment, it could potentially be repurposed for ALS patients far more quickly than a drug developed from scratch—a significant advantage in a disease where time is measured in months.
The finding fits into a broader shift in how researchers think about neurodegenerative disease. Immunotherapy has already transformed cancer treatment and is now showing promise against Alzheimer's disease through monoclonal antibodies that target immune cells. Ajami's work suggests ALS may respond to a similar approach. "It may be similar to what immunotherapy did for cancer or will do for Alzheimer's by targeting immune cells," she said. Yet she was careful not to overstate the implications. "At this point, we cannot say it's a cure but it's a very interesting start."
The next phase of research will involve dose-response studies in the mouse model to determine optimal treatment levels. If those studies succeed, the path to human trials could move relatively quickly, given that the antibody has already cleared FDA safety hurdles. Ajami, who came to OHSU in 2019 after beginning this research as a postdoctoral fellow at Stanford, said her ultimate goal is to see the treatment reach patients. For people living with ALS—a disease that currently has no cure and only one modestly effective drug—even a therapy that slows progression rather than stopping it would represent a meaningful advance.
Notable Quotes
When we blocked its expression in mice, we were able to slow down the disease. We hope that it will get to the clinic very soon.— Bahareh Ajami, senior author, Oregon Health & Science University
At this point, we cannot say it's a cure but it's a very interesting start. It may be similar to what immunotherapy did for cancer or will do for Alzheimer's by targeting immune cells.— Bahareh Ajami
The Hearth Conversation Another angle on the story
Why does blocking this one protein on immune cells actually slow down ALS? What's the mechanism?
The immune system in ALS brains seems to be attacking the wrong targets. These microglial cells and macrophages are becoming overactive and damaging motor neurons. By blocking alpha-5 integrin, you're essentially preventing these immune cells from infiltrating and harming the tissue where they shouldn't be.
But immune cells are supposed to protect us. Why would they turn against motor neurons in the first place?
That's the central mystery of ALS. Something goes wrong—maybe a protein misfolds, maybe there's a genetic predisposition—and the immune system misinterprets it as a threat. The cells rush in to help but end up causing more damage. The antibody doesn't shut down the immune system entirely; it just blocks one pathway these cells use to get where they're going.
The antibody already exists for cancer. Does that mean it works the same way in both diseases?
Not exactly. In cancer, the antibody helps the immune system attack tumor cells. In ALS, we're using it to restrain the immune system from attacking neurons. Same tool, opposite goal. That's what makes repurposing so elegant—and why safety data from cancer trials matters so much here.
How close are we to actual patients taking this drug?
Still several steps away. They need to figure out the right dose in mice first, then move to human trials. But because the antibody is already FDA-approved, they don't have to start from scratch on safety. That could compress years off the timeline.
What happens if it works in humans the way it worked in mice?
You'd have a drug that slows progression rather than stops it. For ALS patients, that's enormous. A few extra months of being able to move, to speak, to breathe on your own—that changes everything.