Generation of induced pluripotent stem cells (iPSCs) from human foreskin fibroblasts

The human iPS cell line VUZUZLi001-A (hVH-1) was generated from human foreskin fibroblasts to be used as a control line. Reprogramming was performed by retroviral transduction of reprogramming factors OCT4, SOX2, KLF4 and c-MYC.Resource tableUnlabelled TableUnique stem cell line identifierVUZUZLi001-AAlternative name(s) of stem cell linehVH-1InstitutionInstitute of Virology and Cell Biology, University of LübeckContact information of distributorJürgen Rohwedel, [email protected] of cell lineiPSCOriginhumanAdditional origin infoAge: unknownSex: maleEthnicity if known: —Cell sourceforeskin fibroblastsClonalitymixedMethod of reprogrammingretroviral integrationGenetic modificationNOType of modificationN/AAssociated diseaseN/AGene/locusN/AMethod of modificationN/AName of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock date2017-08-05Cell line repository/bankN/AEthical approvalEthics Committee University of Lübeck; reference number: 14-10

Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy

Background!#!Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes.!##!Methods!#!In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified.!##!Results!#!Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes.!##!Conclusions!#!An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy

FARS-ADL across Ataxias: Construct Validity, Sensitivity to Change, and Minimal Important Change

BackgroundPatient-focused outcomes present a central need for trial-readiness across all ataxias. The Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS-ADL) captures functional impairment and longitudinal change but is only validated in Friedreich Ataxia. ObjectiveValidation of FARS-ADL regarding disease severity and patient-meaningful impairment, and its sensitivity to change across genetic ataxias. MethodsReal-world registry data of FARS-ADL in 298 ataxia patients across genotypes were analyzed, including (1) cross-correlation with FARS-stage, Scale for the Assessment and Rating of Ataxia (SARA), Patient-Reported Outcome Measure (PROM)-ataxia, and European Quality of Life 5 Dimensions visual analogue scale (EQ5D-VAS);(2) sensitivity to change within a trial-relevant 1-year median follow-up, anchored in Patient Global Impression of Change (PGI-C);and (3) general linear modeling of factors age, sex, and depression (nine-item Patient Health Questionnaire [PHQ-9]). Results FARS-ADL correlated with overall disability (rho(FARS-stage) = 0.79), clinical disease severity (rho(SARA) = 0.80), and patient-reported impairment (rho(PROM-ataxia) = 0.69, rho(EQ5D-VAS) = -0.37), indicating comprehensive construct validity. Also at item level, and validated within genotype (SCA3, RFC1), FARS-ADL correlated with the corresponding SARA effector domains;and all items correlated to EQ5D-VAS quality of life. FARS-ADL was sensitive to change at a 1-year interval, progressing only in patients with worsening PGI-C. Minimal important change was 1.1. points based on intraindividual variability in patients with stable PGI-C. Depression was captured using FARS-ADL (+0.3 points/PHQ-9 count) and EQ5D-VAS, but not FARS-stage or SARA. ConclusionFARS-ADL reflects both disease severity and patient-meaningful impairment across genetic ataxias, with sensitivity to change in trial-relevant timescales in patients perceiving change. It thus presents a promising patient-focused outcome for upcoming ataxia trials. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society