Amyotrophic lateral sclerosis

Research hypothesis. The connection between amyotrophic lateral sclerosis and Alpha-1 Antitrypsin is described in Mark Egly's patent-pending application US20220160847A1 (Appl. No. 17/527,730), a published, patent-pending application that has not been granted. It names ALS among the conditions for which it proposes testing for Alpha-1 Antitrypsin deficiency and giving AAT to people found deficient. This is not established medical fact and is not medical advice. Always talk with your doctor about your own health.

What is amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis is a health condition discussed in Mark Egly's research on Alpha-1 Antitrypsin. It is also known as ALS, Lou Gehrig's Disease. Neurological conditions affect the brain, spinal cord, or nerves. The patent-pending application explores links between AAT and certain neurodegenerative processes.

What Mark Egly's patent-pending application discusses

The patent-pending application proposes that when the body has too little working Alpha-1 Antitrypsin, or when neutrophils release too much neutrophil elastase, inflammation and tissue damage may worsen. For ALS, the patent-pending application suggests that testing for AATD could help guide care. This is a research hypothesis, not a proven treatment path for everyone with this condition.

Selected Scientific Anchors

1. Human observational study (small). In spinal fluid from 15 newly diagnosed ALS patients and age-matched controls, average AAT was about 45% lower in ALS (21.4 vs 38.8 µg/ml, p = 0.013). The inflammatory signal IL-23 was about 31% higher (1647 vs 1259 pg/ml, p = 0.012), and the two moved in opposite directions (r = −0.543, p = 0.036). The authors said raising AAT in the nervous system should be investigated. [1]
2. Human tissue + preclinical (rat). Mast cells and neutrophils were found in muscle from people who died with ALS and along the motor nerves of SOD1G93A rats, supporting a role for neutrophil-related inflammation outside the brain and spinal cord. These studies did not test AAT. [2][3]

How this may relate to Alpha-1

Alpha-1 Antitrypsin (AAT) is best known as an inhibitor of the neutrophil enzymes neutrophil elastase, proteinase 3, and cathepsin G. [C] Because neutrophils appear in ALS-affected nerves and muscle, researchers have asked whether AAT's control of neutrophil enzymes could matter in ALS. This has not been tested in people.

As of 15 October 2026, we found no human clinical trials of Alpha-1 Antitrypsin for ALS registered on ClinicalTrials.gov, and no interventional trials of AAT in ALS.

What you can do

FDA-approved ALS medicines include riluzole and edaravone, and tofersen (Qalsody) for ALS caused by SOD1 gene mutations (accelerated approval, 2023). Keep working with your ALS specialist team.

• Mark Egly's patent-pending application
• Related Conditions
• Self-check tool
• Alpha-1 360
• Contact the foundation
• AATD and neurological conditions

References

[1] Wormser U, Mandrioli J, Vinceti M, Fini N, Sintov A, Brodsky B, Proskura E, Finkelstein Y. Reduced levels of alpha-1-antitrypsin in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a novel approach for a potential treatment. J Neuroinflammation. 2016;13(1):131. doi:10.1186/s12974-016-0589-4. PMID 27245439. Evidence level: Human observational (small). PubMed · DOI

[2] Trias E, King PH, Si Y, et al. Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight. 2018;3(19):e123249. doi:10.1172/jci.insight.123249. PMID 30282815. Evidence level: Human autopsy tissue + preclinical (rat). PubMed · DOI

[3] Trias E, Ibarburu S, Barreto-Núñez R, et al. Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS. JCI Insight. 2017;2(20):e95934. doi:10.1172/jci.insight.95934. PMID 29046475. Evidence level: Preclinical (rat). PubMed · DOI

[C] Janciauskiene S, Welte T. Well-known and less well-known functions of alpha-1 antitrypsin. Its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thorac Soc. 2016;13(Suppl 4):S280-S288. doi:10.1513/AnnalsATS.201507-468KV. PMID 27564662. PubMed · DOI

References checked: 15 October 2026

Research hypothesis. This page is educational only and is not a diagnosis or treatment plan. Alpha-1 Antitrypsin is not an approved treatment for ALS. Continue standard care with your neurologist or specialist team.