This paper gives interesting new info about the nature of PD as an inflammatory disease. IGF-1 (insulin-like growth factor) is generally regarded as a neuroprotective agent and an antioxidant. These authors think that this neuroprotection by IGF-1 is not enough, perhaps indicating that the observed increase would be a compensatory mechanism in controlling inflammation.

From the point of ATH434, an iron chelator, we know that iron overload is causing inflammation and we have iron overload in several places in the PD and MSA brains. ATH434 has demonstrated that it reduces iron in the brains of both PD and MSA animal models but only phase 2 study will answer if it does also in human MSA.

There is a lot to read in this free paper from UK Biobank.

PLoS One

. 2023 May 9;18(5):e0285416.

doi: 10.1371/journal.pone.0285416. eCollection 2023.

Machine learning analysis of the UK Biobank reveals IGF-1 and inflammatory biomarkers predict Parkinson's disease risk

Michael Allwright ¹, Hamish Mundell ², Greg Sutherland ², Paul Austin ¹, Boris Guennewig ¹

Affiliations expand

• PMID: 37159450

DOI: 10.1371/journal.pone.0285416

Abstract

Introduction: Parkinson's disease (PD) is the most common movement disorder, and its prevalence is increasing rapidly worldwide with an ageing population. The UK Biobank is the world's largest and most comprehensive longitudinal study of ageing community volunteers. The cause of the common form of PD is multifactorial, but the degree of causal heterogeneity among patients or the relative importance of one risk factor over another is unclear. This is a major impediment to the discovery of disease-modifying therapies.

Methods: We used an integrated machine learning algorithm (IDEARS) to explore the relative effects of 1,753 measured non-genetic variables in 334,062 eligible UK Biobank participants, including 2,719 who had developed PD since their recruitment into the study.

Results: Male gender was the highest-ranked risk factor, followed by elevated serum insulin-like growth factor 1 (IGF-1), lymphocyte count, and neutrophil/lymphocyte ratio. A group of factors aligned with the symptoms of frailty also ranked highly. IGF-1 and neutrophil/lymphocyte ratio were also elevated in both sexes before PD diagnosis and at the point of diagnosis.

Discussion: The use of machine learning with the UK Biobank provides the best opportunity to explore the multidimensional nature of PD. Our results suggest that novel risk biomarkers, including elevated IGF-1 and NLR, may play a role in, or are indicative of PD pathomechanisms. In particular, our results are consistent with PD being a central manifestation of a systemic inflammatory disease. These biomarkers may be used clinically to predict future PD risk, improve early diagnosis and provide new therapeutic avenues.