What is ALS?

Amyotrophic lateral sclerosis (ALS) severely impacts the individuals who live with it. At Paradromics, our work is centered around alleviating one small part of that: attempting to restore the ability to communicate when ALS has made speaking impossible.

We develop brain-computer interfaces for people living with ALS and other neurodegenerative conditions that affect speech and movement, and our work has brought us close to those within the ALS community. The information below is designed for patients, caregivers, and anyone trying to understand what an ALS diagnosis means, including what to expect, what treatments exist, and where the research is headed.

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified medical professional for diagnosis and treatment.

What Is ALS?

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects motor neurons, which are nerve cells located within the brain and spinal cord responsible for controlling muscle movement. Over time, these neurons break down and deteriorate, causing muscles to weaken, atrophy, and eventually stop functioning altogether.

ALS is also referred to as Motor Neuron Disease (MND), Charcot’s disease, or Lou Gehrig’s disease, named due to the baseball legend originally diagnosed in 1939.

How Common Is ALS?

ALS is relatively uncommon but more widespread than you might realize. Approximately 30,000 people are living with ALS at any given time, and around 5,000 individuals are diagnosed each year.

ALS can develop in anyone – although it most commonly appears between the ages of 40 and 70, and men are diagnosed on a slightly more frequent basis compared to women.

In addition, veterans are diagnosed with ALS at roughly 1.5 times the rate of the general population. The U.S. Department of Veterans Affairs recognizes ALS as a service-connected condition, providing dedicated benefits and care programs for eligible veterans.

Two Types of ALS

There are two main forms of ALS:

• Sporadic ALS accounts for roughly 90% of cases, occurs without a clear family history, and is not inherited.‍
• Familial ALS accounts for about 10% of cases and is caused by inherited gene mutations.

Is ALS Hereditary?

ALS is not typically inherited from a parent, but it can be. Sporadic ALS – the most common form – has no known genetic cause linked to family history.

Familial ALS is hereditary. Out of the more than 40 genes associated with ALS, gene mutations in the C9orf72, SOD1, TARDBP, and FUS genes are the most commonly identified.

ALS Symptoms

Symptoms of ALS are typically gradually occurring and are easy to dismiss early on, as they tend to start in one region of the body and spread to other areas over time.

Early stage, progressing symptoms can include:

• Gradual muscle weakness in the arms, legs, or neck
• Muscle cramps and stiffness (spasticity)
• Twitching in the hands, feet, shoulders, or tongue (called fasciculations)
• Slurred or slow speech
• Difficulty swallowing (dysphagia) or drooling
• Fatigue
• Unintentional emotional expressions, like laughing or crying at unexpected times (pseudobulbar affect)

In addition to physical symptoms, there are also psychological symptoms impacting mental health and emotional states for both ALS patients and their caregivers as they adjust to the diagnosis and work through a treatment plan.

What Does ALS Feel Like in the Beginning?

ALS can be easy to overlook at the onset, as early changes are often subtle enough that they’re initially attributed to fatigue or stress. Many people first notice something that feels “off” – their hand no longer grips as well, their foot drags slightly behind, or their words are harder to get out.

What Causes ALS?

Researchers do not yet know exactly what causes ALS, which is part of what makes it so difficult to treat and why research into each pathway is currently ongoing.

However, current evidence points to a combination of factors:

• Genetics: Gene mutations are found in about 70% of familial cases and 5 to 10% of sporadic cases.
• Environment: Exposure to toxins such as lead or mercury, certain viruses, and physical trauma may contribute.
• Cellular processes: Problems with protein processing, oxidative stress, and inflammation in nerve cells are also currently being studied.

How Is ALS Diagnosed?

There is not a single test or method that is used to diagnose ALS, but rather a comprehensive process of ruling out other conditions and looking for specific patterns across nerve and muscle damage.

A neurologist will typically use:

• Clinical evaluation, including a thorough review of symptoms and medical history.
• Neurological exams to test reflexes, strength, and coordination.
• Electromyography (EMG) tests that use small needles to record electrical activity in muscles in order to detect motor neuron damage.
• MRI scans to rule out other conditions affecting the brain or spinal cord.
• Blood tests and genetic testing, especially when familial ALS is suspected.

Doctors look for evidence of damage to both upper motor neurons (in the brain) and lower motor neurons (in the spinal cord) that progresses over time, as this spreading pattern is a large indicator of ALS.

Additionally, ALS diagnoses can take anywhere from eight to 15 months to complete, as they involve a series of diagnostic processes including visits with multiple specialists, repeated testing, and the slow ruling out of other conditions.

For many individuals and their caregivers, the waiting period can be one of the hardest parts as symptoms progress and answers remain out of reach.

Can ALS Be Stopped If Caught Early?

Currently, no treatment can stop or reverse ALS, and earlier diagnosis cannot change that.

However, earlier diagnosis does matter in other important ways, as it gives patients more time to access clinical trials, initiate treatments that may help slow disease progression, build a caregiver team, and plan for the future before their ability to communicate is impacted.

Is There a Cure for ALS?

As it stands today, there is not a cure for ALS. But new research pathways have developed quite significantly over the last decade, and several treatment options now exist to slow progression and manage symptoms.

Current ALS Treatments and Therapies

Treatment for ALS focuses on two goals: slowing disease progression and managing symptoms to maintain quality of life.

FDA-approved medications

Disease-modifying drugs and medications that may slow ALS progression:

• Riluzole: the first FDA-approved ALS drug; reduces glutamate toxicity in neurons.
• Edaravone (Radicava): an antioxidant shown to slow functional decline in some patients.‍
• Tofersen (Qalsody): approved for people with SOD1 gene mutations; addresses the underlying genetic cause.

There is another drug, Relyvrio, that targets two pathways involved in nerve cell death – however, its FDA approval was withdrawn in 2024 after a confirmatory clinical trial failed to show benefit.

Symptom management medications:

• Nuedexta: treats pseudobulbar affect (uncontrolled laughing or crying).
• Muscle relaxants: for spasticity and cramping.
• Glycopyrrolate: reduces excess saliva.‍
• Gabapentin and other pain management options.

Therapies

A multidisciplinary care team can significantly support someone working through a diagnosis. Key therapies include:

• Physical therapy to help maintain strength and mobility for as long as possible.
• Occupational therapy for support with daily activities and adapting to the home environment.
• Speech therapy to address swallowing difficulties and communication changes.
• Respiratory therapy to manage breathing as it becomes affected.
• Talk therapy or psychological support to help patients and caregivers process grief, anxiety, and the emotional weight of the disease.

Latest Research and Breakthroughs

ALS research has accelerated in recent years, showing particular promise across several distinct areas.

Gene Therapies

Tofersen (Qalsody) represents a meaningful step forward for people with SOD1-ALS, the mutation that causes roughly 2% of all ALS cases. It uses antisense oligonucleotide (ASO) technology to reduce the production of the toxic SOD1 protein. Clinical data suggests it may slow disease progression and improve survival in this population.

Researchers are now developing similar ASO therapies targeting other ALS-related gene mutations, including C9orf72.

Stem Cell Research

Several trials are investigating whether stem cells can protect or replace damaged motor neurons. Results to date are early but encouraging.

Biomarker Development

Better biomarkers (measurable indicators of disease activity in the blood or spinal fluid) are being identified, which may be helpful in attempting to diagnose ALS earlier and track how well treatments are working.

Brain-Computer Interface (BCI) Research

For individuals living with ALS who have lost the ability to speak, clinical trials are underway to test brain-computer interfaces that restore communication directly from neural signals. This is an active area of research, and the Connexus^® BCI (described below) is among the devices in clinical trials.

Assistive Technology for ALS

As ALS progresses, assistive devices become central to maintaining independence and quality of life.

Common technologies include:

• AAC (augmentative and alternative communication) devices ranging from simple letter boards to voice-output tablets. Used to help people communicate when speech becomes difficult.
• Power wheelchairs and accessibility equipment like ramps or lifts.
• Ventilators and respiratory support for breathing difficulties.
• Nutrition and feeding tubes (PEGs) if swallowing becomes too difficult.
• Brain-computer interfaces (BCIs) to help restore communication and autonomy for people in advanced stages of the disease.

The right combination of assistive technology depends on where someone is in their ALS progression and what is most important to them. An occupational therapist or ALS specialist can help evaluate options.

BCIs vs. Traditional AAC Devices

Traditional AAC devices work by detecting residual physical movement, such as eye tracking, head movement, or touch, making them valuable tools that help many people with ALS regain the ability to communicate with loved ones and express their needs.

However, as ALS progresses to later stages, even the smallest of movements may become difficult or impossible. This is where brain-computer interfaces offer something different.

Learn more about how BCIs compare to traditional AAC devices.

How Brain-Computer Interfaces Work for ALS

For people with severe speech-motor impairment – including those in advanced stages of ALS – a brain-computer interface can help restore the ability to communicate without requiring any physical movement.

The Connexus BCI, a high-data-rate brain-machine interface developed by Paradromics, is designed specifically for this population. It is currently an investigational device being studied in clinical trials.

It’s designed around a straightforward principle: go upstream of the muscle damage entirely. How it works:

1. Surgical Placement: A neurosurgeon places three components beneath the skin: the brain interface, a chest transceiver, and a flexible connector. The procedure uses established neurosurgical techniques refined over decades in other health care applications.
2. Neural Signal Capture: Microelectrodes extend just beneath the surface of the brain’s motor cortex, recording electrical activity directly from individual neurons — the signals the brain sends when it tries to speak or move.
3. Wireless Transmission: Data flows through a flexible lead to a chest transceiver, which transmits information via a secure near-infrared optical link to an external device worn by the user. That external device also powers the entire system wirelessly.
4. AI-Powered Translation: A portable computer running advanced neural decoding algorithms receives the data. Machine learning analyzes neural patterns to determine what the user intends to communicate, then translates those intentions into synthesized speech, screen text, or computer commands.

The goal is fully autonomous communication without relying on muscle movement that ALS has taken away.

Clinical Trial: Could the Connexus BCI Be Right for You?

The Connect-One Clinical Study is designed to evaluate safety and potential clinical benefit of the Connexus BCI for restoring communication and enabling computer control in people living with ALS and other motor impairments. It is currently enrolling participants who live within four hours of one of the three clinical sites: University of Michigan, Massachusetts General Hospital (MGH), and UC Davis.

If you or someone you love may be eligible, we encourage you to learn more about the Connect-One Clinical Study and see if you qualify.

Living With ALS: You Are Not Alone

For patients and the people who love and surround them, an ALS diagnosis can change everything, and the losses that come with this disease are profound.

But hope remains, and more people are living longer with ALS than ever before. Treatments are improving, technology is opening new doors, and research is moving faster than it has in decades.

If you or a loved one are looking for support, the ALS Association connects patients and caregivers to local care teams, clinical trials, assistive technology resources, and communities. Alternatively, you can view ongoing clinical trials for ALS treatments and therapies by heading to https://clinicaltrials.gov/.