clemastine / Generic mfg. - LARVOL DELTA

Does Oral Antihistamine Use Reduce the Risk of Salivary Fistula Following Superficial Parotidectomy? A Retrospective Study. (PubMed, Clin Otolaryngol) - "Oral antihistamine use following superficial parotidectomy may significantly reduce the incidence of salivary fistula. Most adverse effects were mild and tolerable. These findings suggest a potential benefit of antihistamines in the prevention of postoperative complications."

Journal • Retrospective data • Oncology • Otorhinolaryngology • Parotid Gland Cancer

Pilot functional magnetic resonance imaging study of clemastine-aided functional recovery on a mouse model of demyelination. (PubMed, Neuroprotection) - "The principal findings of our research include: (1) cuprizone-treated animals suffer an initial phase of elevated connectivity at Week 2 with respect to controls, transitioning to reduced connectivity at Week 5; (2) different temporal trajectories across brain regions, reflecting varying susceptibility to demyelination; (3) while spontaneous remyelination normalizes connectivity in most networks at Week 10 (5 weeks after ceasing cuprizone intoxication), the thalamocortical axis exhibits lasting disruption even 6 months after normalization of diet; and (4) on the contrary, clemastine-aided remyelination re-establishes normal thalamocortical connectivity at 6 months after demyelination. This approach provides insights into the dynamic processes of demyelination and remyelination, informing the development of more effective interventions for MS."

Journal • Preclinical • CNS Disorders • Immunology • Multiple Sclerosis

CCMR Two: A Phase IIa, Randomised, Double-blind, Placebo-controlled Trial of the Ability of the Combination of Metformin and Clemastine to Promote Remyelination in People With Relapsing-remitting Multiple Sclerosis Already on Disease-modifying Therapy (clinicaltrials.gov) - P2 | N=70 | Completed | Sponsor: Cambridge University Hospitals NHS Foundation Trust | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Sep 2025

Trial completion • Trial completion date • CNS Disorders • Multiple Sclerosis

The Cambridge Centre for Myelin Repair trial Two (CCMR Two): a trial protocol for a phase 2a, randomised, double-blind, placebo-controlled clinical trial of the ability of the combination of metformin and clemastine to promote remyelination in people with relapsing-remitting multiple sclerosis already on disease-modifying therapy. (PubMed, Trials) - P2 | "We set out the trial design, the rationale for participant and outcome measure selection, and the pre-specified analyses. With this trial, we expect to be able to detect the structural and functional consequences of remyelination within a sample size feasible for our single-centre trial."

Clinical • Clinical protocol • Journal • P2a data • CNS Disorders • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • Solid Tumor

Carboplatin impairs optic nerve myelination in Neurofibromatosis Type 1 (NF1) by reducing cholesterol levels and inducing oligodendrocyte loss (SNO 2025) - "Our findings revealed that carboplatin induces optic nerve oligodendroglial toxicity in the context of NF1, which can be rescued by clemastine, PLX5622, or dietary cholesterol."

Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Solid Tumor • NF1

Carboplatin impairs optic nerve myelination in Neurofibromatosis Type 1 (NF1) by reducing cholesterol levels and inducing oligodendrocyte loss (WFNOS 2025) - "Our findings revealed that carboplatin induces optic nerve oligodendroglial toxicity in the context of NF1, which can be rescued by clemastine, PLX5622, or dietary cholesterol."

Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Solid Tumor • NF1

Clemastine ameliorates cognitive deficits in an experimental rat model of chronic cerebral hypoperfusion. (PubMed, J Cereb Blood Flow Metab) - "Importantly, pharmacological enhancement of myelination preserved dendritic spine density and prevented synaptic loss, cognitive deficits, and neurovascular dysfunction following BCCAO. These findings suggest that clemastine may represent a promising therapeutic option for CCH-associated cognitive impairment."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Solid Tumor

Clemastine Fumarate Improves Cognitive Function and Prognosis in Patients with Ruptured Intracranial Aneurysms (ChiCTR) - P2/3 | N=190 | Not yet recruiting | Sponsor: The Wuxi No.2 People Hospital (Jiangnan University Affiliated Central Hospital); Wuxi Second People's Hospital (Jiangnan Univers

New P2/3 trial • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology

Enrichment-induced forgetting is associated with white matter microstructure in mice. (PubMed, Behav Brain Res) - "Consistent with the above, administering clemastine fumarate, a pro-myelinating drug, induced forgetting in male mice (β=-23.5%, p=0.009). Neurogenesis, an established mechanism that contributes to forgetting, indexed by the volume of the granule cell layer of the dentate gyrus, independently predicted forgetting (β=-13.6%, p=0.036). These findings indicate that myelin-related plasticity in white matter tracts that support contextual fear memory may play a role in enrichment-induced forgetting."

Journal • Preclinical

Targeting Oligodendrocyte Dysfunction in Alzheimer's Disease: a New Frontier for Drug Repurposing with Antihistamines and Serotonin Receptor Agonists. (PubMed, J Mol Neurosci) - "We discuss pharmacological strategies to correct OL dysfunction by drug repurposing: first-generation H1-antihistamine clemastine, which induces OPC maturation by M1 muscarinic antagonism and ERK/mTOR signalling; H3-receptor antagonists/inverse agonists (e.g. pitolisant) increase neurotransmitter release and induce CREB-mediated remyelination; and serotonergic GPCR agonists (5-HT4, 5-HT6, 5-HT2C) shift APP processing toward non-amyloidogenic pathways, enhance synaptic proteostasis, and protect OLs against 5-HT toxicity. We present a clinical translation roadmap featuring adaptive, biomarker-responsive trials that utilise enhanced myelin imaging; personalised and multi-omics approaches to medicine; and transdisciplinary collaboration among neuroscience, pharmacology, regulatory bodies, and patient-caregiver groups. The translation of repurposed glial-targeting therapies to clinical practice will require adaptive, biomarker-guided trials, advanced myelin imaging, and..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Solid Tumor

Comparative pharmacology of CVL-1001, CVL-2001, and other candidate small molecules for remyelination in multiple sclerosis (ECTRIMS 2025) - "In contrast, clemastine and other tested compounds directed at most alternative mechanisms showed minimal ability to promote formation of new oligodendrocytes... These studies demonstrate that inhibition of cholesterol biosynthesis enzymes, specifically EBP and CYP51, is the predominant mechanism by which small molecules promote oligodendrocyte formation. Convelo's compounds, clinical candidate EBP inhibitor CVL-1001 and lead CYP51 inhibitor CVL-2001, exhibit superior pharmacology and differentiation potency compared to compounds targeting alternative mechanisms. Together, these data provide strong mechanistic validation for EBP and CYP51 as best-in-class targets for remyelination, supporting their continued advancement toward clinical evaluation in MS."

CNS Disorders • Multiple Sclerosis • Solid Tumor

Identification and elucidation of mechanism of a novel small molecule therapy for Multiple Sclerosis (ECTRIMS 2025) - " We tested the potency of a small molecule, CN045, in differentiating primary mouse OPCs expressing EGFP driven by the myelin proteolipid protein promoter (plp-EGFP), human OPCs derived from induced pluripotent stem cells (iPSCs), and adult human OPCs, as well as Cuprizone/Rapamycin induced demyelination/remyelination mouse model. The percentage of plp-EGFP+ rodent cells and MBP immunostained oligodendrocytes were compared to two positive controls (T3 & Clemastine) and DMSO... CN045 is a brain penetrable small molecule that enhances OPC differentiation in vitro and remyelination in vivo. AI based in silico modeling is a promising approach to study the mechanism of CN045 on OPC differentiation and myelination. CN045 and its novel analogs have the potential to enhance remyelination in PwMS."

CNS Disorders • Multiple Sclerosis • Solid Tumor • PLP1

Modulating CNS myelin autoimmune disease using CAR T cells (ECTRIMS 2025) - "Our approach offers a cell-mediated disease model that resembles the lesion structure seen in human MS, is more reproducible than EAE, and can be used a) to test interventions to restore the function of the optic nerve or b) prevent T cell-mediated damage. Clemastine showed to be able to induce remyelination in the context of the lesion during the inflammatory phase of the disease."

CAR T-Cell Therapy • Ataxia • Immunology • Movement Disorders • Ocular Inflammation • Ophthalmology • Optic Neuritis • CD4 • PRKDC

Evaluating the remyelinating efficacy and safety of the combination of metformin and clemastine in people with relapsing remitting multiple sclerosis (CCMR-Two): a randomised, placebo-controlled, double-blind, phase 2 clinical trial. (ECTRIMS 2025) - P2 | "Top-line results of primary and major secondary outcomes, as well as safety data, will be reported in this session. Disclousure of interest: This research is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Cambridge Clinical Research Facility, and the Cambridge Clinical Trials Unit (CCTU). The trial was funded by the UK MS Society.NGC report grants from UK MS Society, during the conduct of the trial."

Clinical • Late-breaking abstract • P2 data • Alzheimer's Disease • Anesthesia • CNS Disorders • Dementia • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pediatrics • Sarcoidosis • Solid Tumor

Bexarotene-induced remyelination promotes neuroprotection in people with relapsing remitting multiple sclerosis (ECTRIMS 2025) - "Our results suggest that remyelination, measured by change in VEP P100 peak time, is associated with neuroprotection following treatment with bexarotene. This aligns with previous findings showing an association between VEP latency and NfL levels in participants treated with clemastine. These conclusions support the role of blood-based neuroaxonal biomarkers for assessment of remyelinating therapies and neuroprotection across future clinical trials."

CNS Disorders • Multiple Sclerosis • NEFL

Integrated Multi-Omics Analysis Reveals Immune and Metabolic Dysregulation in a Restraint Stress-Induced Depression Model. (PubMed, Biomedicines) - "Notably, clemastine exerts its antidepressant-like effects in part by mitigating neuroinflammation and preserving mitochondrial function. These findings provide novel insights into the molecular basis of stress-induced depression and suggest that clemastine is a potential therapeutic candidate."

Journal • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Psychiatry

Sigma-1 receptor counteracts non-cell-autonomous poly-PR-induced astrocytic oxidative stress in C9orf72 ALS. (PubMed, Redox Biol) - "This study identifies Sigma-1R as a critical modulator of non-cell-autonomous poly-PR toxicity and establishes its activation as a potent suppressor of astrocyte-derived oxidative stress. Our findings uncover a previously unrecognized glial mechanism driving C9orf72 ALS pathogenesis and support Sigma-1R activation, via clemastine, as a promising therapeutic strategy to mitigate neuroinflammation and disease progression."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Inflammation • NOX4

Human myelinated brain organoids with integrated microglia as a model for myelin repair and remyelinating therapies. (PubMed, Sci Transl Med) - "Furthermore, the application of the pro-remyelinating compounds clemastine, XAV939, and BQ3020 further enhanced remyelination in MHBOs +MG but was ineffective in the absence of microglia. Cross-validation of our findings in mouse cerebellar slice cultures confirmed that the pro-remyelinating compounds were effective ex vivo, suggesting the translational potential of our MHBOs +MG model."

Journal • CNS Disorders • Multiple Sclerosis

Prenatal valproic acid on the basis of gestational diabetes also induces autistic behavior and disrupts myelination and oligodendroglial maturation slightly in offspring. (PubMed, Transl Psychiatry) - "we delineate the antagonistic effects of GDM and prenatal VPA on ERK phosphorylation in fetal OPCs, consequently altering their proliferation and differentiation, thereby culminating in milder dysmyelination and autistic behaviors."

Journal • Autism Spectrum Disorder • Diabetes • Genetic Disorders • Gestational Diabetes • Metabolic Disorders • Solid Tumor • DUSP5 • HDAC3 • LEP • LEPR

Randomized, cross-over, controlled study of Clomastine fumarate in the treatment of Williams syndrome (ChiCTR) - P2 | N=50 | Completed | Sponsor: Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

New P2 trial • Developmental Disorders

Mitigation of sepsis-induced liver injury by Clemastine via modulating GSDMD/NLRP-3/Caspase-1/NF-κB signalling pathways. (PubMed, Eur J Med Res) - "Finally, by suppressing the NLRP-3/Caspase-1 mediated pyroptotic cell death in rats, CLM pretreatment provided protection against septic-liver damage."

IO biomarker • Journal • Hepatology • Infectious Disease • Liver Failure • Septic Shock • BCL2 • CASP3 • IL18 • IL1B • TNFA

Evaluating the effects of pro-myelinating drugs on motor function and myelination in a zebrafish model of genetic leukoencephalopathy. (PubMed, Neurosci Lett) - "Although Clemastine significantly increased the number of oligodendrocytes, it failed to improve visuomotor function in vps11 mutants. These findings imply that increasing oligodendrocyte numbers does not necessarily result in improved behavioral responses in vps11 mutants."

Journal • CNS Disorders • Developmental Disorders • Solid Tumor

Anxiolytic effects of clemastine via modulation of hippocampal oligodendrocytes in a mouse model of methotrexate-induced cognitive impairment. (PubMed, Neuropharmacology) - "MTX downregulated key myelin-related genes, including Sox10 and Plp, but CLE treatment effectively counteracted this. This in vitro evidence strongly supports our in vivo findings, demonstrating that CLE exerts anxiolytic effects in CRCI by modulating MTX-induced damage to hippocampal oligodendrocytes, thus identifying a specific mechanism for a novel therapeutic strategy."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Mood Disorders • Oncology • Psychiatry • Solid Tumor • SOX10

Hippocampal Oligodendrocytes Regulate Mossy Fiber Development Involved in Epileptic Responses. (PubMed, Neurosci Bull) - "More importantly, enhancing differentiation by orally administered clemastine rescues the defective mossy fiber development in the early postnatal period and attenuates epilepsy susceptibility in adults. Together, these results strongly suggest that an OL differentiation defect in the hippocampus may contribute to susceptibility to epilepsy in adults."

Journal • CNS Disorders • Epilepsy • Solid Tumor

Rocuronium-Induced anaphylactic shock with reversal after the use of sugammadex: a case report (Euroanaesthesia 2025) - "His medical history included hypertension (treated with enalapril) and smoking. He reported an allergy to ibuprofen (hives) and a previous uncomplicated orthopedic surgery under GA. GA was induced with 50ug of fentanyl, 80mg of lidocaine, 160mg of propofol, 20mg of ketamine and 100mg of rocuronium followed by orotracheal intubation...Anaphylactic shock was suspected, and treatment with adrenaline ev (3 bolus of 0,1mg), 200mg of hydrocortisone ev, 2mg of clemastine ev, IV fluids, and bronchodilators was initiated... Anaphylactic shock was attributed to rocuronium, a rare but life-threatening complication of GA that requires prompt recognition and intervention, even in patients with no previous issues. If suspected, the administration of sugammadex may be crucial for stabilizing the patient."

Case report • Clinical • Anesthesia • Cardiovascular • Dermatology • Gastroenterology • Hypertension • Hypotension • Immunology • Orthopedics • Urticaria