Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS)

Abstract

A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22-0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50-1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.

Amyotrophic lateral sclerosis (ALS), cancer, autoimmunity and metabolic disorders: An unsolved tantalizing challenge

“…In this field, our group is currently working on the design of new retinoid agonists as potential treatments for the disease (data not published). tes was associated with a twofold reduction in the risk of ALS (Kioumourtzoglou et al, 2015). The pathophysiological mechanism of diabetes might account for this discrepancy.…”

“…This relationship might reveal important clues about the novel mechanisms involved and the protective or deleterious role of antineoplastic treatments, as new immunotherapeutic drugs, which are or particular interest. In this regard, Kuczmarski et al (2017) performed a case‐control study involving 414 ALS patients and 361 controls. Interestingly, a history of chemotherapy treatment was significantly associated with a decreased ALS risk, while no significant association between the risk of disease and immunosuppressant therapy use was observed.…”

Medication use and risk of amyotrophic lateral sclerosis—a systematic review

“…Regarding immunosuppressants, a Dutch populationbased case-control study found a 74% reduced ALS risk in relation to the use of immunosuppressive drugs (OR = 0.26, 95% CI 0.08-0.86) [9]. A US case-control study [17] and a German case-control study [22] failed however to observe an association between immunosuppressant use and ALS. The US study did report a lower ALS risk among individuals with a history of chemotherapy (OR = 0.46, 95% CI 0.22-0.89) [17].…”

“…Two studies examined steroids [22,24] and five have evaluated the relationship of non-steroidal anti-inflammatory drugs (NSAIDs) [14-16, 22, 24] in relation to risk of ALS, among which four studies examined aspirin [14][15][16]24]. In addition, three studies assessed the association between immunosuppressant use as a broad category and ALS risk [9,17,22] whereas two studies explored antibiotic use in relation to ALS risk [6,18], focusing on a broad category of drugs or sub-class or individual drugs.…”

Biochemistry of Drugs Action and their Resistance Mechanism: A Brief Discussion

“…Cancer is uncontrolled division of the cell due to mutation in any cancer signaling pathway (Kuczmarski et al, 2017). Any disturbance in the S phase, G phase and M phase of cell leads to formation of tumors neoplastic cells along with metastatic cancer (Lam et al, 2020).…”