May Is ALS Awareness Month: What You Need to Know

Amyotrophic lateral sclerosis, or ALS, destroys the nerve cells that control voluntary movement, gradually stripping away the ability to walk, speak, swallow, and eventually breathe. May has been designated ALS Awareness Month in the United States, and the timing matters: ALS remains widely misunderstood, often diagnosed late, and dramatically underfunded relative to its severity. Understanding the disease better equips people to recognize early symptoms, support those living with it, and follow the research breakthroughs that are, for the first time, beginning to target its root causes.

What ALS Does to the Body

Motor neurons are among the largest cells in the nervous system. They run from the brain down through the spinal cord and out to muscles, carrying the signals that let you grip a cup, climb stairs, or form words. In ALS, these cells degenerate and die. The muscles they once controlled weaken, twitch, and eventually stop working. The disease hits both upper motor neurons (in the brain) and lower motor neurons (in the spinal cord and brainstem), which is part of what distinguishes it from other neurological conditions.

Researchers have identified several reasons motor neurons are especially vulnerable. They are physically enormous cells with heavy metabolic demands to maintain their structure. They depend heavily on well-functioning mitochondria for energy. They are unusually sensitive to a process called excitotoxicity, where excessive signaling chemicals damage the cell. And they have a limited ability to repair misfolded or damaged proteins compared to other cell types.¹

One of the most consistent findings across ALS research is the role of a protein called TDP-43. In healthy cells, TDP-43 sits in the nucleus doing essential work with RNA. In the vast majority of ALS cases, TDP-43 clumps together in the wrong part of the cell and gets depleted from the nucleus. This dual problem creates toxicity from the clumps and a loss of normal function from the missing protein.² Recent work has connected TDP-43 mislocalization to the loss of a specific enzyme called ASRGL1, opening another line of inquiry into what triggers the cascade.³

These processes do not operate in isolation. Oxidative stress, inflammation, problems with how cells transport materials along their axons, and the excitotoxicity mentioned above all feed into one another. Excessive glutamate signaling leads to calcium flooding into motor neurons, which damages mitochondria, which generates reactive oxygen species, which further disrupts glutamate handling. The result is a self-reinforcing cycle of damage.⁴

How Common Is ALS

ALS is considered a rare disease, but it is not as uncommon as many people assume. A global meta-analysis estimated the worldwide incidence at roughly 1.6 new cases per 100,000 people per year, with an overall prevalence of about 4.4 per 100,000.⁵ Those averages mask wide geographic variation. Reported incidence ranges from as low as 0.26 per 100,000 in Ecuador to over 23 per 100,000 in parts of Japan, and point prevalence in the United States has been estimated as high as roughly 12 per 100,000.⁶ Some of that variation reflects genuine differences in risk, while some reflects differences in how thoroughly countries track neurological diseases.

Both incidence and prevalence climb with age, peaking in the 70-to-79 age group.⁵ ALS can strike younger adults, but it does so less frequently. Men develop the disease somewhat more often than women overall, though the gap narrows with age.

Recognizing the Symptoms

About two-thirds of people with typical ALS start with what clinicians call “limb onset,” meaning the first noticeable problems are in an arm or a leg: a weakening grip, foot drop, trouble with buttons, or unexplained muscle wasting. These symptoms may appear on one side of the body first and can start either close to the torso or further out at the hands and feet.⁷

The remaining roughly one-third begin with “bulbar onset,” where the first symptoms involve speech and swallowing. Slurred speech, difficulty chewing, or choking on liquids can precede limb weakness by months. In most bulbar-onset cases, arm and leg symptoms develop within a year or two.⁷ In rare cases, the disease first presents with breathing difficulty, which is particularly prone to misdiagnosis.

Muscle twitching (fasciculations) and cramping are common early features. Pain is not traditionally listed as a primary symptom, but many people with ALS experience it, often from muscle stiffness, joint strain, or immobility. The disease does not typically affect the senses: vision, hearing, touch, and taste generally remain intact, and bladder and bowel control are usually preserved until very late stages.

Why Diagnosis Takes So Long

One of the most frustrating aspects of ALS is the delay between when symptoms start and when the correct diagnosis is made. Across Europe and the United States, a large chart review found the average time from symptom onset to ALS diagnosis was about eight months. For people who received at least one wrong diagnosis first, that stretched to over ten months on average. About 35% of patients reviewed had been initially misdiagnosed.⁸

There are several reasons for this. ALS is rare enough that most primary care doctors will see very few cases in an entire career, making early recognition difficult. The symptoms overlap with far more common conditions. Limb-onset patients, for instance, are frequently diagnosed first with degenerative spine disease or peripheral neuropathy.⁹ Some undergo unnecessary surgeries as a result: one earlier study found that 43% of patients were initially misdiagnosed, and several had spinal surgeries before the true diagnosis was identified.¹⁰

There is no single definitive test for ALS. Diagnosis relies on clinical examination, electromyography, imaging to rule out other conditions, and observation over time. Physicians identified the similarity of ALS symptoms to other diseases, combined with delayed referral to neurologists, as the primary barriers to a timely diagnosis.⁸ This is one reason awareness campaigns matter: the earlier someone with progressive, unexplained weakness or speech changes reaches a neurologist, the sooner appropriate care can begin.

Emerging Blood-Based Biomarkers

One development that could eventually shorten diagnostic delay is the use of neurofilament light chain (NfL) as a biomarker. Neurofilaments are structural proteins inside nerve cells, and when those cells are damaged or dying, neurofilament fragments leak into the cerebrospinal fluid and blood. In ALS, blood levels of NfL run about four times higher than in healthy people. In one study, a blood test for NfL distinguished people with ALS from healthy controls with about 90% sensitivity, and levels remained relatively stable over time, making them useful for tracking the disease rather than just catching a snapshot.¹¹

NfL is not specific to ALS alone; other neurological diseases can raise it too. But it is proving especially useful as a prognostic tool. People with the highest NfL levels at the time of diagnosis had a substantially higher risk of death during follow-up, which helps clinicians and families plan ahead.¹¹ It is also being used to gauge whether experimental treatments are actually reducing nerve damage, which makes it a valuable tool in clinical trials.

Genetics and Who Gets ALS

About 5 to 10 percent of ALS cases are classified as familial, meaning there is a clear inherited pattern. The rest are considered sporadic, though the line between the two is blurrier than it once appeared, since some apparently sporadic cases carry genetic risk variants.

The most common genetic cause is a repeated DNA sequence in the C9orf72 gene. Healthy people have a short stretch of a six-letter repeat in this gene; people with the disease-linked mutation can carry hundreds or even thousands of copies. This expansion causes harm through multiple routes: it reduces the amount of normal C9orf72 protein the cell can make, and it also generates toxic RNA clusters and abnormal proteins that accumulate in the brain.¹² The C9orf72 expansion is also linked to frontotemporal dementia, which is discussed below.

Mutations in the SOD1 gene were the first to be linked to ALS in the early 1990s and remain among the best understood. Mutated SOD1 protein tends to misfold and clump together, and not all mutations behave the same: some are associated with rapid disease progression, while others allow longer survival. How damaging a specific mutation is can be partly predicted by its effect on protein structure and its tendency to promote aggregation.¹³ Laboratory work has shown that SOD1 mutants form abnormal clusters held together by both chemical bonds and structural interactions between protein units.¹⁴ Understanding the SOD1 pathway has proved critical, because it became the first ALS subtype to get a targeted therapy.

Environmental Risk Factors

Genetics is only part of the picture. Environmental exposures have been linked to increased ALS risk, and the evidence is strongest for pesticides, heavy metals, and certain occupational chemical exposures. In a case-control study, reported pesticide exposure was associated with roughly five times the odds of developing ALS. Military service was also associated with higher risk across multiple time windows, and blood measurements showed elevated levels of persistent organic pollutants in ALS patients.¹⁵

Military veterans have drawn particular attention. Exposures during service, including burn pits, engine exhaust, firing range dust, and certain chemicals including Agent Orange, have all been associated with increased ALS risk among service members.¹⁶ In the general population, specific occupations such as truck driving and airline piloting, which involve chronic exposure to exhaust or metals, have also been flagged.¹⁷ Head trauma is another factor that appears repeatedly in risk analyses. None of these exposures guarantee ALS on their own, but for people with underlying genetic susceptibility, they may help push the disease process over the threshold.

Current Treatments

For decades, ALS treatment meant a single drug: riluzole. Riluzole works primarily by dampening excessive glutamate signaling, which is the excitotoxicity process described earlier. At the doses used clinically, it modestly extends survival, typically by a few months. That may sound small, but in a disease with a median survival of roughly two to five years, it is not trivial.¹⁸

Edaravone, an antioxidant drug, was approved for ALS more recently. It aims to reduce oxidative damage to motor neurons, particularly in the early stages of the disease.¹⁹ Its benefit appears most pronounced in a subset of patients with relatively early and well-defined disease, and it remains controversial among some clinicians because the pivotal trial was small and narrowly focused on a specific patient population.

The genuinely new chapter in ALS treatment is gene-targeted therapy. Tofersen is the first drug approved specifically for ALS caused by SOD1 mutations. It is an antisense oligonucleotide, meaning it is a short strand of synthetic genetic material designed to intercept the messenger RNA made from the mutant SOD1 gene and trigger its destruction. Delivered by injection into the spinal fluid, tofersen substantially reduces SOD1 protein levels in the cerebrospinal fluid and lowers neurofilament levels in the blood.²⁰

The initial 28-week controlled trial did not show a statistically significant difference in clinical function scores between tofersen and placebo, which raised questions. But longer-term follow-up told a different story. Over nearly three years, people who started tofersen early showed less decline in function, respiratory capacity, muscle strength, and quality of life compared to those who started later. Tofersen also prolonged survival relative to what would be expected from the natural history of SOD1-related ALS.²¹ SOD1 mutations account for only a small fraction of all ALS, so tofersen helps a limited number of people directly. But the approach represents proof of concept that attacking a known genetic cause can alter the disease course, and similar strategies are being explored for C9orf72-related ALS and other genetic subtypes.²²

The Cognitive Side People Don’t Expect

ALS has long been thought of as a purely motor disease, but that picture is incomplete. A meaningful proportion of people with ALS develop cognitive or behavioral changes consistent with frontotemporal dysfunction. These can include difficulty with planning, language fluency, decision-making, or social behavior. In some cases, the changes meet the criteria for frontotemporal dementia.²³

ALS and frontotemporal dementia share overlapping pathology, including TDP-43 accumulation, and the C9orf72 genetic expansion is a common cause of both. In some patients, the dementia appears first and ALS follows; recognizing that connection can lead to earlier detection of motor symptoms.²⁴ For families, knowing that personality changes or apathy are part of the disease rather than a separate problem can be important both for care planning and for emotional understanding.

Multidisciplinary Care and Survival

Because ALS has no cure and existing drugs provide modest benefit, much of the difference in how long and how well someone lives with the disease comes down to supportive care. Multiple studies have shown that coordinated, multidisciplinary care, where a neurologist, respiratory therapist, speech-language pathologist, nutritionist, physical therapist, and social worker all contribute to a shared plan, significantly improves survival.

A comparative study between Ireland and Northern Ireland found that patients who attended a centralized multidisciplinary ALS clinic had a substantially lower risk of death than those who received community-based care.²⁵ A Spanish study similarly found a six-month survival gain associated with multidisciplinary care, driven primarily by timely introduction of non-invasive ventilation and gastrostomy feeding.²⁶ In practical terms, the two biggest levers appear to be breathing support and adequate nutrition. Both sound straightforward, but getting them introduced at the right time and maintained consistently requires a team that is watching closely.

The Financial and Emotional Toll on Families

ALS is among the most expensive diseases to manage. As the person with ALS loses independence, family members typically become primary caregivers. A French survey found that 88% of patients relied on family caregiver support, overwhelmingly from spouses. The combined annual burden of out-of-pocket medical costs and lost income from changes to employment, for both patient and caregiver, averaged over €15,000 per year.²⁷

The emotional toll is just as significant. Caregiver anxiety is one of the strongest predictors of overall burden, including the strain of managing personal life alongside caregiving responsibilities and the weight of the role itself.²⁸ Resources like respite care, mental health support for caregivers, and connection with ALS advocacy organizations are not extras; they are essential parts of managing the disease.

Communication Technology for Late-Stage ALS

One of the cruelest aspects of ALS is that it can lock a fully conscious mind inside a body that can no longer move or speak. Conventional communication aids, like eye-tracking devices, depend on the user retaining at least some reliable muscle control. For people whose disease progresses to the point where even eye movement becomes unreliable, those devices fail.²⁹

Brain-computer interfaces, or BCIs, aim to bridge that gap by reading electrical signals directly from the brain and translating them into computer commands. In a landmark case, a fully implanted BCI allowed a patient with late-stage ALS to type independently at roughly two letters per minute by attempting hand movements that the implanted electrodes detected and converted to cursor control. The system supplemented and sometimes replaced the patient’s eye-tracking device.³⁰ Two letters per minute is slow, but for someone who otherwise has no way to express a thought, it is transformative. BCI technology is still in its early stages of clinical application, but the pace of development is accelerating, and trials are actively exploring both implanted and non-invasive designs for ALS communication.³¹