MedicalResearch.com Interview with:
Alastair J. Noyce MD, PhD
Preventive Neurology Unit,
Wolfson Institute of Preventive Medicine
Queen Mary University of London,
Department of Clinical and Movement Neurosciences,
University College London, Institute of Neurology,
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Amyotrophic lateral sclerosis (ALS) or motor neurone disease (MND) is a relentlessly progressive disorder that affects nerves which supply muscles. Over time the nerves die, leading to limb weakness, speech and swallowing problems, and ultimately breathing problems. Patients die on average 3-5 after diagnosis. There is no cure and the underlying disease processes are only understood in part.
In this study, we adopted a large-scale approach to exploring causal risk factors for ALS. Causality is important because it implies that if one could modify or induce a change in a risk factor, one would observe a change in the risk of ALS. Observational studies struggle to prove causality definitely. Associations in observational studies can arise because:
1) the risk factor truly changes risk of ALS; or
2) something about ALS changes one’s exposure to the risk factor; or
3) the presence of another factor, which may or may not be known, can induce an association between a risk factor and ALS. Unless scenario 1 represents the truth, then changing the risk factor will not have any effect on risk of ALS.
We used a proxy-based approach, known as Mendelian randomisation, to assess hundreds of possible risk factors for ALS for evidence of causality. What emerged from this was a very clear signal linking LDL cholesterol to risk of ALS.
MedicalResearch.com: What should readers take away from your report?
Response: Mendelian randomisation is just one tool we can use for finding causal risk factors, but it is very helpful because it helps clarify some of the inconsistencies we have previously seen linking cholesterol to ALS in observational studies. If true, then we already have well established drugs that target and reduce LDL cholesterol, such as Statins.
This gives us further inspiration to study the pathways affected in ALS but also hope that preventive strategies may be plausible. Of course, more work needs to be done to better understand our observations from this study, but the note is one of cautious optimism.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The next steps will include further study of whether lowering levels of cholesterol might have a protective effect against MND and potentially evaluating the use of cholesterol-modifying drugs such as Statins in people at risk of motor neurone disease or soon after diagnosis.
Ann Neurol. 2019 Feb 5. doi: 10.1002/ana.25431. [Epub ahead of print]
Bandres-Ciga S1, Noyce AJ2,3, Hemani G4, Nicolas A5, Calvo A6, Mora G7; ITALSGEN Consortium; International ALS Genomics Consortium, Tienari PJ8, Stone DJ9, Nalls MA1,10, Singleton AB1, Chiò A6,11,12, Traynor BJ5,13.
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