Lesabelimab

Subcutaneous foslevodopa/foscarbidopa (LDp/CDp) infusion is approved for treating motor fluctuations and dyskinesias in patients with advanced Parkinson’s disease (aPD). However, efficacy data on non-motor symptoms (NMS) are limited.

To evaluate the effects of LDp/CDp treatment on NMS in patients with aPD.

Retrospective analysis of efficacy of LDp/CDp on NMS after 3 week therapy in a Parkinson’s day-clinic setting and further 6 weeks of outpatient treatment.

Twenty-one patients with aPD were assessed at baseline (T0), after 3 weeks (T1), and after 9 weeks (T2). Assessments included broader NMS according to MDS-UPDRS Part I and NMS questionnaire (NMSQ) and in more detail sleep (PDSS-2) and depression (BDI-2).

Mean MDS-UPDRS I total score significantly improved by 27% at T1 and 34% at T2 (3.90 and 4.85 points, respectively), which has to be considered clinically relevant (threshold -2.64 points). Relevant improvement accounted for 62% of patients at T1 and 57% at T2.MDS-UPDRS part IB score also improved significantly at both timepoints by approximately 30%. The greatest benefits were observed in sleep disturbances, pain, and constipation. NMSQ score improved by 21% at T1 and 27% at T2, particularly within the gastrointestinal domain. PDSS-2 score improved by 27% at T1, and Beck Depression Inventory 2 score by 37% at T1; both showed numerical but non-significant trends at T2. Psychotic symptoms occurred as adverse effects in 4 of 21 patients (19%).

In this exploratory retrospective cohort, LDp/CDp therapy improved clinically relevant NMS, though confirmation in larger controlled studies is needed.

Food-derived dietary polysaccharides have attracted increasing attention as functional ingredients for ulcerative colitis (UC) management. In this study, a homogeneous polysaccharide, designated LDP, was isolated from the bulbs of Lilium davidii var. willmottiae (Lanzhou lily). Structural analyses showed that LDP had a weight-average molecular weight (M_W) of 5.082 × 10³ g/mol and was mainly composed of alternating →4)-α-D-Manp-(1 → and →4)-β-D-Glcp-(1 → residues with minor branching. Conformational analysis and molecular dynamics (MD) simulations indicated that LDP adopted an extended semi-flexible coil conformation in aqueous solution. In dextran sulfate sodium (DSS)-induced colitis mice, LDP markedly alleviated disease symptoms, as evidenced by improved survival, reduced body weight loss, a lower disease activity index and attenuated histopathological injury. Mechanistically, LDP enhanced intestinal barrier integrity, significantly increased acetic acid levels and partially restored short-chain fatty acid (SCFA)-associated beneficial taxa, including Lactobacillaceae, Bifidobacterium, Allobaculum and members of Erysipelotrichaceae/Erysipelotrichia. Integrated metagenomic, proteomic, Western blot and immunological analyses further indicated that LDP attenuated intestinal inflammation by suppressing the TAB1/MAP2K4-centered MAPK signaling pathway, as evidenced by reduced TAB1 and MAP2K4 expression and decreased p38 phosphorylation, and by restoring the Th17/Treg balance in mesenteric lymph nodes (MLNs). These findings suggested that LDP alleviated DSS-induced colitis through coordinated regulation of gut microbiota, microbial metabolism, MAPK inflammatory signaling and mucosal immunity.