Longitudinal Quantitative MRI Provides Responsive Outcome Measures for Early and Late Muscle Changes in ALS.

Introduction/aims: Studies have demonstrated the potential of muscle MRIs to measure disease progression in ALS. However, the responsiveness and utility of quantitative muscle MRIs in an ALS clinical trial remain unknown. This study aimed to determine the responsiveness of quantitative muscle MRIs to measure disease progression in ALS.

"Havana Syndrome": A post mortem.

Background: Since 2016, an array of claims and public discourse have circulated in the medical community over the origin and nature of a mysterious condition dubbed "Havana Syndrome," so named as it was first identified in Cuba. In March 2023, the United States intelligence community concluded that the condition was a socially constructed catch-all category for an array of health conditions and stress reactions that were lumped under a single label.

Aims: To examine the history of "Havana Syndrome" and the many factors that led to its erroneous categorization as a novel clinical entity.

MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease affecting motor neurons and characterized by microglia-mediated neurotoxic inflammation whose underlying mechanisms remain incompletely understood. In this work, we reveal that MAPK/MAK/MRK overlapping kinase (MOK), with an unknown physiological substrate, displays an immune function by controlling inflammatory and type-I interferon (IFN) responses in microglia which are detrimental to primary motor neurons. Moreover, we uncover the epigenetic reader bromodomain-containing protein 4 (Brd4) as an effector protein regulated by MOK, by promoting Ser-phospho-Brd4 levels.

Moderate intrinsic phenotypic alterations in ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features.

While motor and cortical neurons are affected in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, ALS/FTD iPSC-MG mono-cultures form GC repeat RNA foci, exhibit reduced C9orf72 protein levels, and generate dipeptide repeat proteins.