Glossary

The words that come up most in ALS research, explained without jargon.

"Slower decline" percentages: When a trial reports "30% slower decline", it means the ALSFRS-R score fell about 30% less over the trial than in the placebo group. For example, losing 7 points instead of 10. It does not mean 30% of people improved, or that the disease stopped. These percentages come from different trials with different patients and lengths, so they cannot be compared directly.
Accelerated approval: An FDA pathway that allows earlier approval based on a biological marker (like neurofilament) that is reasonably likely to predict benefit. The company must then confirm the benefit in further studies.
ALS: Amyotrophic lateral sclerosis, also called motor neurone disease (MND) or Lou Gehrig's disease. The nerve cells that control muscles (motor neurons) gradually stop working, which leads to weakness and loss of movement, speech, swallowing and breathing.
ALSFRS-R: The ALS Functional Rating Scale, Revised. A 12-question score (0 to 48) about everyday abilities such as speaking, swallowing, walking, dressing and breathing. Higher is better. On average, people with ALS lose roughly one point per month, though this varies a lot. Most trials ask whether a drug slows how fast this score drops.
Antisense oligonucleotide (ASO): A short, man-made strand of genetic material that lowers production of a specific harmful protein. In ALS, ASOs are usually given by spinal injection (intrathecal).
Expanded access: Also called compassionate use or early access. A way for some people who can't join a trial to get an unapproved drug, if the company agrees and regulators allow it. Availability varies by drug and country.
HEALEY ALS Platform Trial: A large trial run by Massachusetts General Hospital that tests several drugs at once against a shared placebo group, so more drugs can be tested faster.
Independent study: A study run by universities, hospitals, governments or charities rather than the company that makes the drug. Company-run trials are essential and carefully regulated, but independent studies are an important check.
Intrathecal: Given by injection into the fluid around the spinal cord, through a lumbar puncture.
Neurofilament light (NfL): A protein released into blood and spinal fluid when nerve cells are damaged. Lower levels suggest less ongoing damage. It is used as an early signal of whether a drug is having a biological effect.
Open-label: A study where everyone knows who gets the drug, often with no placebo group. Useful for safety, but results are easily influenced by expectations and can't prove the drug works.
PALS and CALS: People living with ALS (PALS) and their caregivers (CALS).
Phase 1: The first tests in people, usually a small group. The main question is whether the drug is safe and what dose to use.
Phase 2: A medium-sized trial (often 50 to 300 people) that checks safety and looks for early signs that the drug works. Many drugs that look promising in Phase 2 do not succeed in Phase 3.
Phase 3: A large trial (often hundreds of people) designed to prove whether the drug works. Positive Phase 3 results are usually needed for approval.
Placebo: A dummy treatment that looks like the real drug but has no active ingredient. Comparing a drug against placebo is the most reliable way to tell whether it really helps.
Primary endpoint: The main question a trial is designed to answer, fixed before the trial starts (for example, change in ALSFRS-R after 48 weeks). If a trial "missed its primary endpoint", it did not show the effect it was designed to show.
Real-world study: A study of people who took a drug as part of normal care, compared with similar people who did not. No placebo is used, so it is less reliable than a randomised trial, but a large, well-run real-world study by independent researchers can show whether a drug's benefit holds up outside the original trial.
Signal (on this site): Our measure of how often, and how reliably, a company publicly updates on its ALS drug. It combines how recent the last update was, how many updates there were in the last 12 months, and whether announced milestones were delivered on time. It says nothing about whether the drug works.
SOD1, FUS, C9orf72: Genes that, when altered, can cause ALS. Gene-targeted drugs, such as antisense oligonucleotides, are designed for people who carry a specific gene change. Genetic testing tells you whether these trials could apply to you.
Sporadic and familial ALS: About 90% of people have sporadic ALS, with no family history. About 10% have familial ALS, which runs in families. Several genes are known, including C9orf72, SOD1, FUS and TARDBP. Some drugs target only one genetic form.
Subgroup or post-hoc analysis: Looking at results for only part of the trial population (for example, people who started treatment early), often after the results are known. These findings can point the way, but they are less reliable because looking at enough slices of data will find something by chance. They need to be confirmed in a new trial.
Topline results: The first headline results a company announces after a trial ends, usually in a press release, before the full data is published and reviewed by independent scientists.