👤 Sebastian Götze

Anti-amyloid monoclonal antibodies, including lecanemab and donanemab, are now available for the treatment of Alzheimer's disease (AD). Defining real-world patient eligibility and identifying barriers to access are critical for their effective implementation in routine clinical practice. Retrospective observational multicenter study of patients who underwent CSF AD biomarker testing at Lariboisière Hospital (Paris, France) from 2023 to 2024, assessing lecanemab eligibility using CLARITY AD trial criteria and the French Memory Clinic Federation appropriate use recommendations (AURs) following EMA authorization. From a source population of 3075 patients, 676 underwent CSF testing, and 356 had biomarker-confirmed AD; 315 patients with MRI, APOE status, and MMSE data available (mean age 73.2 ± 8.1 years; 47.8% female; median MMSE 22 [IQR 19-26]) were screened. Using CLARITY AD trial criteria, 90 patients (28.6%) were eligible; low MMSE scores and MRI findings were the most frequent exclusion criteria. French AURs reduced eligibility to 75 patients (23.8%), excluding patients with a CSF A + T - profile and APOE ε4 homozygotes. Eligibility did not differ by age group. Eligibility rates from the entire source population equated to only 2.9% of patients using the CLARITY AD criteria and 2.4% using the French AURs. At follow-up, 34.5% of initially eligible patients no longer met the MMSE eligibility criteria. In specialized settings, lecanemab eligibility remained limited, highlighting the need for early AD diagnosis and efficient screening pathways. Show less

Identification of carbohydrate sequences that determine affinity to specific chemokines is a critical step for strategies to interfere with chemokine-mediated leukocyte trafficking. Here, we first characterized the development of allergic asthma in Tie2-dependent and inducible Ext1-knockout (Tie2-Ext1(iKO)) mice. We showed that heparan sulfate is essential for leukocyte recruitment in the peribronchial region and bronchoalveolar lavage fluid (BALF), and is crucial for induction of airway hyperresponsiveness. Our glycan microarray showed a unique affinity profile of chemokine CCL20 to substructures of heparin and heparin-like oligo/di/monosaccharides. Among them, we identified a synthetic and not naturally occurring monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA), as a potential inhibitor for CCL20-heparan sulfate interaction. Mice injected with Di-S-IdoA via tail vain or nasal inhalation showed attenuated leukocyte recruitment into inflammatory sites and BALF. These results demonstrate a critical role of chemokine-heparan sulfate interaction in the asthma development and Di-S-IdoA as a potential drug for asthma treatment. Show less