ALS: What We Know Now About Its Causes, Treatments, and Future Hope

1. What You’ll Learn From This Article

This article breaks down recent research on amyotrophic lateral sclerosis (ALS)—a rare, progressive neurodegenerative disease—to explain its causes, how it affects the body, and what’s new in treatment and care. We’ll cover key findings from a 2023 review of ALS research, including:

• The role of genetics and proteins in ALS
• How the immune system contributes to the disease
• Current treatments and promising new therapies
• Tools doctors use to diagnose and track ALS
• What this means for patients and families navigating the condition

Our goal is to make complex science easy to understand, so you can feel more informed about ALS and better prepared to discuss options with your healthcare team.

2. A Quick Look at ALS

ALS (also called Lou Gehrig’s disease) damages motor neurons—the nerve cells that control muscles. As these cells die, people with ALS lose the ability to move, speak, eat, and eventually breathe. It’s rare (affecting about 2 in 100,000 people worldwide) but devastating: most people live 2–5 years after diagnosis, though some survive longer.

ALS can start with subtle symptoms (like muscle weakness in a hand or foot) and progress quickly. There’s no cure yet, but research is advancing fast—offering hope for better treatments and, one day, a cure.

3. Why Summarizing ALS Research Is Important

ALS research is vast and constantly evolving. Studies are done in labs, hospitals, and clinics around the world, but findings are often scattered in scientific journals. Reviews like the one we’re discussing bring this information together, helping patients, families, and even doctors:

• Understand how ALS develops
• Learn about new treatments being tested
• Know what questions to ask during doctor’s visits
• Stay hopeful about future breakthroughs

For rare diseases like ALS, this kind of “big picture” summary is critical—every bit of knowledge helps improve care.

4. What Current Research Says About ALS (The Core Findings)

The 2023 review we’re exploring dives deep into four key areas of ALS research: genetics, protein “clumping” (proteinopathy), immunity, and treatments/biomarkers. Here’s what you need to know:

A. Genetics: Why Some People Get ALS

About 10% of ALS cases are familial (run in families), caused by mutations (changes) in genes like C9ORF72, SOD1, and TDP-43. These mutations disrupt how cells work—for example, C9ORF72 mutations lead to toxic proteins that damage neurons.

Most ALS cases (90%) are sporadic (no clear family link). Researchers think these are caused by a mix of genetics and environmental factors (like exposure to toxins or trauma), but we still don’t know exactly why they happen.

What this means: Genetic testing can help families with a history of ALS understand their risk. For sporadic cases, more research is needed to uncover triggers.

B. Proteinopathy: The “Clumping” That Harms Cells

A key hallmark of ALS is TDP-43—a protein that normally helps cells process RNA (genetic material). In ALS, TDP-43 misfolds and forms clumps (aggregates) in motor neurons. These clumps:

• Stop the protein from doing its job (a “loss of function”)
• Damage cells by interfering with other processes (a “gain of toxic function”)

TDP-43 clumping is found in 97% of ALS patients and 50% of people with frontotemporal dementia (FTD)—a related condition—linking the two diseases.

What this means: Targeting TDP-43 (e.g., preventing clumping or clearing aggregates) is a major focus of new therapies.

C. Immunity: The Double-Edged Sword

The immune system plays a tricky role in ALS. On one hand, microglia (brain immune cells) and T cells (blood immune cells) can protect neurons by clearing debris and toxins. On the other hand, overactive immune cells can release harmful chemicals that damage neurons—making inflammation a key driver of ALS progression.

Research shows that:

• In ALS mice, reducing harmful immune activity slows disease progression
• In humans, changes in immune cells (like fewer “regulatory T cells”) are linked to faster decline

What this means: Therapies that “rebalance” the immune system (e.g., boosting protective cells or calming overactive ones) are being tested in clinical trials.

D. Treatments & Biomarkers: What Works Now (and What’s Next)

Current Treatments

There’s no cure for ALS, but two drugs are FDA-approved to slow progression:

• Riluzole: Reduces glutamate (a chemical that damages neurons) – extends life by 3–6 months.
• Edaravone: Fights oxidative stress (cell damage from free radicals) – helps slow decline in some patients.

Other treatments focus on managing symptoms (e.g., muscle relaxants, breathing support).

Promising New Therapies

Researchers are testing dozens of new treatments, including:

• Gene therapy: Targets specific mutations (e.g., SOD1 or C9ORF72) to fix faulty genes.
• Antisense oligonucleotides (ASOs): Drugs like tofersen block toxic proteins from being made – early trials show reduced nerve damage in SOD1-mutant ALS.
• Stem cell therapy: Uses healthy cells to replace damaged motor neurons – still in early stages but showing promise.

Biomarkers: Tools to Diagnose & Track ALS

Biomarkers are “flags” in blood, cerebrospinal fluid (CSF), or imaging that signal disease activity. Key ALS biomarkers include:

• Neurofilaments: Proteins released when nerve cells die – high levels in blood/CSF indicate faster progression.
• STMN2: A protein needed for nerve growth – low levels are linked to TDP-43 damage.
• TDP-43 aggregates: Detected in CSF – could help diagnose ALS earlier.

What this means: Biomarkers help doctors diagnose ALS faster (reducing “diagnostic delay”) and track how well treatments work in clinical trials.

5. What This Means for Patients and Families

The research summarized here offers both hope and clarity for people living with ALS:

• Genetics: If you have a family history of ALS, genetic testing can help you understand your risk and guide family planning.
• Proteinopathy: Therapies targeting TDP-43 are in development—this is a major step toward stopping ALS progression.
• Immunity: New immunotherapies could reduce inflammation and protect neurons.
• Treatments: While current drugs don’t cure ALS, they can slow decline—every month of extra time matters.
• Biomarkers: Faster diagnosis means earlier access to treatments and clinical trials.

Most importantly, this research shows that ALS is not a “one-size-fits-all” disease. Doctors are moving toward personalized medicine—treating patients based on their unique genetics, protein changes, and immune profiles.

6. Gaps in Our Knowledge & Future Directions

Despite progress, there’s still much we don’t know about ALS:

• Why do some people with ALS live longer than others? (e.g., Stephen Hawking survived 55 years with ALS.)
• What triggers sporadic ALS? (Environmental factors like toxins or trauma are suspected but not proven.)
• How can we stop TDP-43 clumping for good? (Early therapies show promise, but we need more data.)
• Can we repair damaged motor neurons? (Stem cell therapy is a hope, but it’s not yet ready for widespread use.)

Future research will focus on:

• Early detection (using biomarkers)
• Personalized treatments (targeting specific genetic/protein changes)
• Combining therapies (e.g., gene therapy + immunotherapy)
• Understanding how ALS interacts with other conditions (like FTD)

7. Key Points to Remember

• ALS is a complex disease caused by a mix of genetics, protein damage, and immune system changes.
• Current treatments slow progression but don’t cure ALS—new therapies are in development.
• Biomarkers (like neurofilaments) help diagnose ALS faster and track disease activity.
• The immune system plays a dual role—protecting and harming neurons.
• Research is moving toward personalized medicine, which could improve outcomes for patients.

8. Talk to Your Doctor

This article summarizes the latest ALS research, but every patient’s journey is unique. Use this information to:

• Ask about genetic testing (if you have a family history of ALS)
• Discuss new treatments or clinical trials you’ve read about
• Learn how biomarkers can help track your disease
• Explore symptom management options

Your healthcare team is your best resource—they can help you navigate the latest research and make decisions that are right for you.

Remember: ALS research is advancing faster than ever. While there’s no cure yet, every study brings us one step closer to better treatments—and, one day, a cure.