Ospolot (sultiam) / AOP Orphan Pharma - LARVOL DELTA

Epilepsy with myoclonic-atonic seizures: a comprehensive review with emphasis on current and emerging pharmacotherapies. (PubMed, Expert Rev Neurother) - "Treatment is reviewed hierarchically, from valproate, clobazam, levetiracetam and ethosuximide as commonly used first- and second-line agents to the ketogenic diet, cannabidiol, felbamate, and sulthiame for drug-resistant disease. Although approximately two-thirds of patients with EMAtS achieve seizure remission, a substantial minority experience drug-resistant seizure, intellectual disability, and behavioral comorbidities, underscoring the importance of timely diagnosis, appropriate pharmacotherapy, and early consideration of the ketogenic diet in drug-resistant cases. As precision therapeutics advance, syndrome-based care will increasingly be complemented by treatments tailored to the specific genetic etiology."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • CHD2 • SLC2A1 • XBP1

Pharmacotherapy in obstructive sleep apnoea: a clinical guide. (PubMed, Sleep Breath) - "This review provides a practical, endotype-aligned summary of pharmacologic options for the management of OSA."

Journal • Review • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Carbonic Anhydrase I and II as Biomarkers and Therapeutic Targets in Human Disease: From Physiology to Clinical Translation. (PubMed, Int J Mol Sci) - "CA II emerges as the more established pharmacological target, particularly in glaucoma, with acetazolamide and sultiame showing therapeutic potential in obstructive sleep apnea and possible contributions to epilepsy and neurodegeneration through pH regulation, bicarbonate-dependent signaling, and mitochondrial function. CA I instead appears more valuable as a disease-associated biomarker, especially in disorders involving erythrocyte turnover, inflammation, anemia, and malignancy, though circulating CA I may be confounded by hemolysis and altered erythrocyte dynamics. Clinical translation requires isoform-selective modulators, tissue-targeted delivery, standardized biomarker assays, and mechanistic models distinguishing primary CA involvement from secondary disease-related changes."

Biomarker • Journal • Review • Alzheimer's Disease • Atherosclerosis • Cardiovascular • CNS Disorders • Epilepsy • Genetic Disorders • Glaucoma • Hematological Disorders • Metabolic Disorders • Obesity • Obstructive Sleep Apnea • Oncology • Ophthalmology • Respiratory Diseases • Sleep Disorder

Challenges and opportunities for developing selective carbonic anhydrase inhibitors and activators for vertebrate isoforms. (PubMed, Enzymes) - "Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors of the sulfonamide/sulfamate type, such as acetazolamide, thiazides/high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, antiepileptics (sulthiame, topiramate, zonisamide), or non-steroidal anti-inflammatory agents such as celecoxib and polmacoxib, are effective inhibitors of most CA isoforms present in vertebrates but their clinical use in various pathologies is associated with side effects. Significant efforts were done in the last decades for developing isoform-selective inhibitors for all 12 catalytically active mammalian isoforms, with important results being obtained by using the tail approach or by the discovery of new inhibitory chemotypes, such as the coumarins and their derivatives, the boron/selenium-containing compounds, etc. SLC-0111, an antitumor sulfonamide in clinical development is an example of a successful strategy emerged by using the tail approach, this..."

Journal • Review • CNS Disorders • Cognitive Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Oncology • Post-traumatic Stress Disorder • Psychiatry

Carbonic anhydrases I and II. (PubMed, Enzymes) - "Many CA inhibitors are in clinical use for the management of such conditions, among which are acetazolamide, thiazides and high-ceiling diuretics, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, and antiepileptics such as sulthiame, topiramate and zonisamide, whereas SLC-0111 is in clinical development as an antitumor agent. CA activators are not yet used clinically, but they might have pharmacological applications in the management of neurodegeneration, emotional memory disorders, obsessive-compulsive disorders, phobias, generalized anxiety, and post-traumatic stress. Finding novel modulators of activity for these enzymes may lead to innovative therapeutic applications and deepen our understanding of enzymes, their inhibitors, and their activators."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Epilepsy • Genetic Disorders • Glaucoma • Hypertension • Immunology • Inflammatory Arthritis • Mood Disorders • Neuralgia • Obesity • Obsessive-Compulsive Disorder • Obstructive Sleep Apnea • Oncology • Ophthalmology • Osteoporosis • Pain • Post-traumatic Stress Disorder • Psychiatry • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sleep Disorder

Pharmacologic Treatment for Obstructive Sleep Apnea in Older Adults. (PubMed, Drugs Aging) - "The carbonic anhydrase inhibitor sulthiame has demonstrated dose-dependent improvements in obstructive sleep apnea severity with well-tolerated outcomes. Ultimately, older patients have unique diagnostic and management considerations, warranting further study of obstructive sleep apnea pharmacotherapy to assess age-specific efficacy and outcomes."

Journal • Review • CNS Disorders • Depression • Obesity • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Obstructive sleep apnea and epilepsy comorbidity: possible complications and treatment options (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Additionally, carbonic anhydrase inhibitors, commonly used to manage focal epileptic seizures, have shown beneficial effects on obstructive sleep apnea, rendering them a viable pharmacological alternative for treating OSA in epilepsy patients. This effect is most pronounced for sultiame."

Journal • CNS Disorders • Epilepsy • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Pharmacological treatment of obstructive sleep apnea syndrome (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Until recently, pharmacological management was limited to nasal decongestants for rhinitis exacerbation and modafinil for daytime sleepiness...This review summarizes recent advances in OSAS drug therapy, primarily based on randomized clinical trials, with a focus on agents such as semaglutide, tirzepatide, atomoxetine-oxybutynin, solriamfetol, sultiame, and acetazolamide, as well as established drugs. Further research with long-term follow-up and consideration of OSAS endotypes and drug side effects is needed. The importance of combining different therapeutic approaches for OSAS is emphasized."

Clinical • Journal • Inflammation • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

SYNERGY OSA (clinicaltrialsregister.eu) - P1/2 | N=50 | Active, not recruiting | Sponsor: Vaestra Goetalandsregionen | Recruiting ➔ Active, not recruiting

Enrollment closed • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Influence of hepatic steatosis on antiseizure drug metabolism: in vitro evidence from differentiated HepaRG cells. (PubMed, Toxicol Lett) - "Hepatic steatosis selectively alters the metabolism of carbamazepine and levetiracetam in vitro without enhancing short-term cellular toxicity. These findings raise concerns about possible modifications in drug exposure, efficacy and tolerability in patients with MASLD, and underscore the need for further in vivo and clinical studies."

Journal • Preclinical • CNS Disorders • Epilepsy • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • CYP3A4

Epilepsy in TET3-Related Beck-Fahrner Syndrome: A Case Report and Literature Review (AES 2025) - "One patient developed drug-resistant epilepsy and required sultiame and steroids to abort the seizures (Beck et al...Another patient received pulse steroid and IVIG prior to starting dual antiseizure medications of valproic acid and clobazam (Sager et al... Patients with BEFHARS exhibit a heterogenous spectrum of seizures types and EEG abnormalities, with generalized tonic-clonic seizures and focal discharges being the most commonly reported. While our patient responded well to monotherapy with levetiracetam, the literature had instances of drug-resistant epilepsy requiring immunomodulatory therapies. Clinicians need to remain vigilant and consider individualized management strategies when addressing epilepsy in patients in BEHARS."

Case report • Clinical • Review • CNS Disorders • Epilepsy • Genetic Disorders

EPIPOP: Population Pharmacokinetics of Antiepileptic in Pediatrics (clinicaltrials.gov) - P=N/A | N=753 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy • Pediatrics

Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial. (PubMed, Lancet) - P2 | "Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness. These findings offer perspectives for a pharmaceutical approach to treatment of patients with obstructive sleep apnoea."

Journal • P2 data • Excessive Daytime Sleepiness • Infectious Disease • Novel Coronavirus Disease • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Developmental and epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS): Clinical and treatment insights from a cohort of 50 children. (PubMed, Seizure) - "D/EE-SWAS is a spectrum disorder with variable severity and prognosis depending on etiology. Early recognition and tailored treatment, especially in children with SeLFE, are essential to mitigate neurocognitive decline. This large single-center cohort provides new insights into the therapeutic challenges and outcome variability in D/EE-SWAS."

Journal • CNS Disorders • Epilepsy • Pediatrics

Pharmacotherapy for obstructive sleep apnea: a critical review of randomized placebo-controlled trials. (PubMed, Sleep Med Rev) - "Weight-loss agents, particularly tirzepatide, represent a promising and now clinically viable treatment option. While endotype-targeted approaches are conceptually attractive, many agents were too early in their testing/re-purposing phase to demonstrate improvements in sleepiness, quality of life or sustained reductions of OSA severity; or were insufficiently targeted at the endotype they might best treat."

Journal • Review • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Reduction of carbonic anhydrase activity is associated with amelioration of obstructive sleep apnea. (PubMed, Sleep Breath) - "CA-inhibitory drugs reduced CA activity in whole blood suggesting a therapeutic role of CA inhibition in OSA. The findings also suggest that an activated CA system may constitute a pathophysiological mechanism in some forms of OSA."

Journal • CNS Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Apnea-hypopnea duration changes after Sulthiame - a new biomarker for treatment efficacy? (WSS 2025) - P2 | "STM is associated with a reduction in sleep-disordered breathing, improved nocturnal oxygenation, and a mild prolongation of residual events. The extension of AH event duration with STM should be further explored as a potential biomarker of treatment efficacy in OSA."

Biomarker • Clinical • CNS Disorders • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Identification of CNKSR2 Pathogenic Variant and Detection of Strong XCI in a Female Patient With Severe DEE-SWAS and Phenotype Expansion in Male Patients. (PubMed, Clin Genet) - "Her clinical symptoms were more severe than those of previously reported female patients, but they improved with ethosuximide and sulthiame treatment. The strength of the X-chromosome inactivation skewing may be related to severity. These novel pathogenic CNKSR2 variants have expanded the phenotypic spectrum of this disease."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation

SURF: Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: University Hospital, Angers | Trial completion date: Nov 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Loss-of-function variant in KCNH3 is associated with global developmental delay, autistic behavior, insomnia, and nocturnal seizures. (PubMed, Seizure) - "Our results propose KCNH3, which is primarily expressed in the nervous system, as a new disease gene associated with a neurodevelopmental phenotype including seizures."

Journal • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Insomnia • Mental Retardation • Sleep Disorder • KCNH2 • KCNH3

The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnoea. (PubMed, ERJ Open Res) - "STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained 2 weeks after treatment completion, suggesting prolonged effects of STM in OSA."

Biomarker • Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder • HIF1A

Late Breaking Abstract - A randomized, double-blind, placebo controlled, dose-finding trial of sulthiame in obstructive sleep apnea (ERS 2024) - "STM, in the evaluated dose range, provides a consistent reduction of sleep disordered breathing and improvement of sleep quality, hypoxia, and daytime sleepiness. STM is a promising candidate for drug therapy in OSA."

Clinical • Late-breaking abstract • Cardiovascular • Fatigue • Obstructive Sleep Apnea • Pain • Respiratory Diseases • Sleep Disorder

The effect of sulthiame on potential biomarkers in moderate to severe obstructive sleep apnea (ERS 2024) - "STM treatment in OSA induced a reduction of both CA activity and HIF-1α concentration. The effects remained two weeks after treatment completion, suggesting prolonged effects of STM in OSA."

Biomarker • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • HIF1A

SURF: Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: University Hospital, Angers | Trial completion date: Sep 2024 ➔ Nov 2024 | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

The epilepsy phenotype of KCNK4-related neurodevelopmental disease. (PubMed, Seizure) - "Gain-of-function variants in KCNK4 cause a spectrum of epilepsies, ranging from benign isolated epilepsy to epileptic encephalopathy, with focal to bilateral tonic-clonic seizures being the most commonly observed. Importantly, a subgroup of patients present with a mild extra-neurological phenotype without characteristic facial dysmorphism or generalized hypertrichosis. This report expands the phenotypic spectrum of KNCK4-associated disease and provides new insights into the clinical heterogeneity of this rare neurodevelopmental syndrome."

Journal • CNS Disorders • Dermatology • Developmental Disorders • Epilepsy • Mental Retardation • Pain • Psychiatry • KCNK4