Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.

BACKGROUND: Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures. This trial studied the effects of 12-week iCR on metabolic, immunological, and clinical outcomes in pwMS. METHOD: Relapsing-remitting MS participants were randomised to iCR or a control group. Study visits were conducted at baseline, 6 and 12 weeks. The primary outcome was reduction in serum leptin levels at 12 weeks. Feasibility and safety were assessed by diet adherence and adverse events (AEs). Secondary outcomes included changes in anthropometric and body composition measures, metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate outcome differences between and within groups over time. RESULTS: Forty-two pwMS were randomised, 34 completed the study (17/group). Leptin serum levels at 12 weeks were significantly lower in the iCR versus the control group (mean decrease -6.98 µg/dL, 95% CI: -28.02 to 14.06; p=0.03). Adherence to iCR was 99.5% and 97.2% at 6 and 12 weeks, respectively, and no serious AEs were reported. An increase in blood CD45RO+ regulatory T-cell numbers was seen after 6 weeks of iCR. Exploratory cognitive testing demonstrated a significant improvement in the Symbol Digit Modality Test Score in the iCR group at 12 weeks. CONCLUSIONS: iCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS. TRIAL REGISTRATION NUMBER: NCT03539094 .

Prevalence of anti-myelin oligodendrocyte glycoprotein antibodies across neuroinflammatory and neurodegenerative diseases.

Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in patients with CNS diseases, including MS and ALS. In total, 771 serum samples from the John L. Trotter MS Center and the Northeast ALS Consortium were examined using a live cell-based assay for detection of anti-MOG IgG1. Samples from three cohorts were tested in blinded fashion: healthy control (HC) subjects, patients with clinically diagnosed MOGAD, and an experimental group of ALS and MS patients. All samples from established MOGAD cases were positive for anti-MOG antibodies, while all HC samples were negative. Anti-MOG IgG1 was detected in 65 of 658 samples (9.9%) from MS subjects and 4 of 108 (3.7%) samples from ALS subjects. The presence of serum anti-MOG IgG1 in MS and ALS patients raises questions about the contribution of these antibodies to disease pathophysiology as well as accuracy of diagnostic approaches for CNS inflammatory diseases.

Functional outcomes of diets in multiple sclerosis (FOOD for MS): Protocol for a parallel arm randomized feeding trial for low glycemic load and calorie restriction.

BACKGROUND: Pilot trials indicate that both a low glycemic load (GL) diet and calorie restriction (CR) can be implemented successfully in people with multiple sclerosis (pMS) and may improve MS symptoms and physical function, but large randomized clinical trials (RCTs) have not yet been conducted. The purpose of this study is to test these interventions alone and in combination to determine their efficacy for improving clinical and patient reported outcomes (PROs) in pMS. METHODS: This 32-week, two-arm, RCT at two centers will randomly assign 100 adults with relapsing-remitting or secondary progressive MS to a low GL diet (n = 50) or a standard GL diet (n = 50). Both diet groups will complete two study phases: a eucaloric phase (16 weeks) and a CR phase (16 weeks). Groceries for the study meal plans will be delivered to participants' homes weekly. The primary outcome is physical function, measured by timed 25-ft walk test. Secondary outcomes are pain, fatigue, mood, and anxiety. DISCUSSION: This will be the most rigorous intervention trial to date of a low GL diet and CR in adults with MS, and among the first to assess the impact of intentional weight loss on MS symptoms. Results will provide valuable insight for recommending dietary change, weight loss, or both to adults with MS. These non-drug interventions pose few risks and have potential to yield significant improvements in MS symptoms. TRIAL REGISTRATION ID: NCT05327322.

Sex differences in plasma proteomic markers in late-life depression.

Previous studies have shown significant sex-specific differences in major depressive disorder (MDD) in multiple biological parameters. Most studies focused on young and middle-aged adults, and there is a paucity of information about sex-specific biological differences in older adults with depression (aka, late-life depression (LLD)). To address this gap, this study aimed to evaluate sex-specific biological abnormalities in a large group of individuals with LLD using an untargeted proteomic analysis. We quantified 344 plasma proteins using a multiplex assay in 430 individuals with LLD and 140 healthy comparisons (HC) (age range between 60 and 85 years old for both groups). Sixty-six signaling proteins were differentially expressed in LLD (both sexes). Thirty-three proteins were uniquely associated with LLD in females, while six proteins were uniquely associated with LLD in males. The main biological processes affected by these proteins in females were related to immunoinflammatory control. In contrast, despite the smaller number of associated proteins, males showed dysregulations in a broader range of biological pathways, including immune regulation pathways, cell cycle control, and metabolic control. Sex has a significant impact on biomarker changes in LLD. Despite some overlap in differentially expressed biomarkers, males and females show different patterns of biomarkers changes, and males with LLD exhibit abnormalities in a larger set of biological processes compared to females. Our findings can provide novel targets for sex-specific interventions in LLD.