Early Clues for ALS: What a Mouse Study Teaches Us About Potential New Treatments

If you or a loved one is affected by amyotrophic lateral sclerosis (ALS), you know how urgent the search for effective treatments is. A recent study in mice offers promising insights into a potential new way to target ALS—using a drug already approved for allergies. But before we get ahead of ourselves, let’s break down what this research means (and what it doesn’t) for people living with ALS.

What You’ll Learn

This article explores a mouse study that tested whether a common antihistamine, desloratadine, could slow ALS progression. We’ll cover:

• Why scientists use mice to study ALS
• What the researchers found (and how it might relate to human biology)
• Critical caveats: Why these results don’t mean a cure is around the corner

Animal studies are an early step in research. They help scientists understand how diseases work and test ideas—like new drugs—before they’re tried in humans. But mice are not small humans, and findings in animals often don’t translate directly to people. This study is a clue, not a solution.

A Quick Look at ALS

ALS is a fatal neurodegenerative disease that destroys motor neurons—cells in the brain and spinal cord that control muscle movement. As these cells die, people with ALS lose the ability to walk, talk, eat, and eventually breathe.

• Prevalence: About 2–3 people per 100,000 are living with ALS worldwide.
• Current treatments: Only two drugs (riluzole and edaravone) are approved, and they only slow progression slightly—most people die within 3–5 years of diagnosis.
• Key challenge: Scientists still don’t fully understand why motor neurons die, but factors like abnormal protein buildup (e.g., mutated SOD1), inflammation, and oxidative stress (cell damage from free radicals) are thought to play roles.

Why Scientists Use Mouse Models for ALS Research

Mice are a powerful tool for studying ALS because:

1. Genetic similarity: Mice can be engineered to carry human ALS-related mutations (like the hSOD1G93A gene, which causes 20–25% of familial ALS cases). These “ALS mice” develop symptoms similar to humans, including muscle weakness and motor neuron loss.
2. Controlled environment: Researchers can test drugs or therapies in a consistent, ethical way before moving to human trials.
3. Speed: Mice have short lifespans (about 2 years), so scientists can observe disease progression and treatment effects quickly.

This study used hSOD1G93A mice—one of the most widely used models for familial ALS—to test desloratadine.

What the Study Investigated (and Found)

The researchers wanted to know if desloratadine—a drug commonly used to treat allergies (e.g., hay fever, hives)—could slow ALS in mice. Desloratadine works by blocking a receptor called 5HTR2A, which is involved in inflammation and cell signaling.

Key Methods

• Mice: hSOD1G93A mice (genetically engineered to have ALS-like symptoms) and healthy “wild-type” mice.
• Treatment: Mice were given desloratadine (20 mg/kg/day) by mouth starting at 8 weeks old (before symptoms appeared) for 10 weeks or until death.
• Measures: Researchers tracked ALS onset (using a rotarod test to measure balance), lifespan, motor function (grip strength, gait), muscle damage, and spinal cord changes (motor neuron loss, inflammation).

Key Results in Mice

The study found that desloratadine:

1. Delayed ALS onset: Mice treated with desloratadine developed symptoms (like falling off the rotarod) ~6–8 days later than untreated mice.
2. Prolonged lifespan: Treated mice lived ~5–6 days longer on average.
3. Improved motor function: They had better grip strength, more normal gait, and less muscle atrophy (shrinking) in the gastrocnemius (calf) muscle.
4. Protected motor neurons: The spinal cords of treated mice had fewer dead or damaged motor neurons.
5. Reduced inflammation and oxidative stress: Desloratadine lowered levels of inflammatory proteins (e.g., IL-1β, NLRP3) and markers of cell damage (e.g., MDA) in the spinal cord.
6. Boosted autophagy: This is the cell’s “garbage disposal” system—desloratadine helped clear abnormal hSOD1G93A protein buildup, a key driver of ALS in this model.

How It Worked

Desloratadine’s effects were linked to its ability to block the 5HTR2A receptor on astrocytes—support cells in the brain and spinal cord that become overactive in ALS. Overactive astrocytes release harmful inflammatory molecules and contribute to motor neuron death. By blocking 5HTR2A, desloratadine:

• Reduced astrocyte activation
• Activated a signaling pathway (cAMP/AMPK) that promotes autophagy and reduces inflammation
• Protected motor neurons from damage

What This Means (and What It Doesn’t) for Humans

Potential Clues for ALS Research

This study offers several promising takeaways for scientists:

• 5HTR2A as a new target: The 5HTR2A receptor on astrocytes may be a key player in ALS progression. Blocking it could slow inflammation and protein buildup.
• Repurposing existing drugs: Desloratadine is already FDA-approved for allergies, which means it has a known safety profile. Repurposing drugs can speed up the path to human trials (since researchers don’t have to start from scratch).
• Astrocytes matter: ALS is often thought of as a “motor neuron disease,” but this study highlights the role of supporting cells (astrocytes) in driving damage. Targeting astrocytes could be a new strategy for treatment.

Critical Caveats (Please Read This!)

This study does NOT mean desloratadine is a cure for ALS in humans. Here’s why:

1. Mice are not humans: The hSOD1G93A mouse model mimics familial ALS (caused by a specific gene mutation), but most ALS cases (85–90%) are “sporadic” (no known cause). Results from this model may not apply to all people with ALS.
2. Dose and delivery: The dose of desloratadine used in mice is much higher than what humans take for allergies. We don’t know if the same effects would occur at safe human doses.
3. Early-stage research: This is a preclinical study—meaning it’s done in animals, not people. Even if a drug works in mice, it may fail in human clinical trials (which test safety and efficacy in people). For example, many drugs that slow ALS in mice have not worked in humans.
4. No human data: There are no studies yet testing desloratadine in people with ALS. Until then, we can’t know if it will help (or if it will have side effects).

Next Steps in Research

To move from mouse findings to human treatments, scientists need to:

1. Confirm results in other models: Test desloratadine in other ALS mouse models (e.g., those with TDP-43 mutations, which are common in sporadic ALS) to see if the effects are consistent.
2. Study mechanisms in human cells: Use human stem cells (e.g., motor neurons or astrocytes from people with ALS) to understand how desloratadine works in human biology.
3. Phase 1 clinical trials: If preclinical results hold, test desloratadine in a small group of people with ALS to check safety and dose.
4. Phase 2/3 trials: Larger trials to test whether desloratadine actually slows ALS progression in humans.

This process can take 5–10 years or more—and there’s no guarantee of success. But every preclinical study like this brings us one step closer to understanding ALS.

Key Points to Remember

• What the study found: Desloratadine slowed ALS progression in hSOD1G93A mice by reducing inflammation, boosting autophagy, and protecting motor neurons.
• What it means for humans: This is a promising clue about a new target (5HTR2A) and a potential repurposed drug (desloratadine). But it’s not a treatment for people with ALS yet.
• Why caution is needed: Mice are not humans, and most drugs that work in animals don’t work in people. More research is required before desloratadine can be considered for ALS.

Following Future Research

If you’re interested in tracking ALS research progress, here are some reputable sources to follow:

• ALS Association: Provides updates on clinical trials and research breakthroughs.
• National Institutes of Health (NIH): Funds most ALS research in the U.S.—check their ALS Research Program for updates.
• Journal articles: Look for studies in journals like Nature Neuroscience or JAMA Neurology (but remember, most are technical and require interpretation).

Remember: Research is a marathon, not a sprint. Every study—even those with “negative” results—helps scientists refine their understanding of ALS and move closer to effective treatments.

For now, the best way to support people with ALS is to advocate for more research funding, participate in clinical trials (if eligible), and access existing supportive care (e.g., physical therapy, speech therapy) to improve quality of life.

If you or a loved one is living with ALS, know that you’re not alone—and that scientists are working tirelessly to find answers.