Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model.
Document Type
Article
Abstract
OBJECTIVE: The objective of this study was to use a novel combined pharmacoepidemiologic and amyotrophic lateral sclerosis (ALS) mouse model approach to identify potential motor neuron protective medications.
METHODS: We constructed a large, population-based case-control study to investigate motor neuron disease (MND) among US Medicare beneficiaries aged 66 to 90 in 2009. We included 1,128 incident MND cases and 56,400 age, sex, race, and ethnicity matched controls. We calculated MND relative risk for >1,000 active ingredients represented in Part D (pharmacy) claims in 2006 to 2007 (>1 year before diagnosis/reference). We then applied a comprehensive screening approach to select medications for testing in SOD1
RESULTS: We observed previously established medical associations for MND and an inverse dose-response association between lovastatin and MND, with 28% reduced risk at 40 mg/day. In SOD1
INTERPRETATION: Lovastatin reduced the risk of ALS in humans, which was confirmed in an ALS mouse model by delayed symptom onset, prolonged survival, and preservation of motor neurons. Although further studies to understand the mechanism are required, lovastatin may represent a potential neuroprotective therapy for patients with ALS. These data demonstrate the utility of a combined pharmacoepidemiologic and mouse model approach. ANN NEUROL 2023.
Publication Date
1-10-2023
Publication Title
Annals of neurology
ISSN
1531-8249
PubMed ID
36627836
Digital Object Identifier (DOI)
10.1002/ana.26600
Recommended Citation
Kreple, Collin J; Searles Nielsen, Susan; Schoch, Kathleen M; Shen, Tao; Shabsovich, Mark; Song, Yizhe; Racette, Brad A; and Miller, Timothy M, "Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model." (2023). Neurology. 1305.
https://scholar.barrowneuro.org/neurology/1305