Cerebrospinal Fluid of ALS Patients Has Reduced Levels of Anti-Inflammatory Protein, Revealing Potential New Therapeutic Target
Researchers from the Institute of Drug Research at the The Hebrew University in Israel have revealed that patients with amyotrophic lateral sclerosis (ALS) have low levels of the anti-inflammatory protein alpha-1-antitrypsin (AAT) in their cerebrospinal fluid (CSF).
The findings have been published in the Journal of Neuroinflammation in the study “Reduced levels of alpha-1-antitrypsin in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a novel approach for a potential treatment,” and suggest that AAT may be a potential new therapeutic target for patients with this disease.
ALS is an incurable, neurodegenerative disease characterized by the death of motor neurons that affects two to three per 100,000 individuals worldwide. A large number of evidence points to the involvement of inflammatory processes in ALS development and progression. ALS patients have been shown to have brain infiltration of T-cells, and their prognosis is dependent on the amount of regulatory T-cells. A variety of pro- and anti-inflammatory molecules have also been shown to have altered levels in the cerebrospinal fluid of ALS patients.
AAT is an immuno-modulatory molecule that prevents pathological tissue disruption and controls the release of pro-inflammatory molecules and the function of some immune cells. Decreased levels of AAT have been associated with inflammation-related diseases, such as diabetes, rheumatoid arthritis, or fibromyalgia.
To assess if the levels of AAT were also disrupted in ALS, the researchers examined cerebrospinal fluid samples from 15 newly diagnosed ALS patients at the Center of the Modena University Neurological Department in Italy from 2001 to 2011, who underwent lumbar puncture as a diagnostic procedures. The 14 age-matched controls were patients who were admitted to the same department during the same period, and underwent lumbar puncture due to suspected, but later unconfirmed, neurological disease.
Results revealed that AAT levels in the cerebrospinal fluid of ALS patients were 45 percent lower than in healthy individuals. The level of the pro-inflammatory cytokine interleukin-23 (IL-23) was also measured, revealing a 30.8 percent increase in ALS patients versus healthy subjects.
This was the first study showing a significant reduction of AAT levels in cerebrospinal fluid of ALS patients, which is inversely correlated with the increase of IL-23 in these patients, providing further evidence that ALS is linked with the inflammatory pathways. The researchers believe that if this data is confirmed in larger studies, AAT may represent a novel therapeutic target for ALS.