Nypta (tideglusib) / AMO Pharma, ASD Therap - LARVOL DELTA

Tideglusib-loaded chitosan-incorporated bacterial cellulose hydrogel for enhanced palatal wound healing. (PubMed, Int J Biol Macromol) - "Pairwise comparisons demonstrated significant differences between the baseline and Td + Hydrogel groups only. Topical use of chitosan incorporated BC-based hydrogel loaded with Td suggested a beneficial impact on the healing of palatal mucosal wounds in rats."

Journal • Pain

Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies. (PubMed, Int J Mol Sci) - "ASOs aim to reduce toxic RNA accumulation, CRISPR-based approaches aim to excise or correct the expanded CTG repeats, and repurposed small-molecule drugs, such as vorinostat, tideglusib, and metformin, could serve as potential therapeutic agents for DM1 patients with cardiac complications. More research and well-designed clinical trials are urgently needed to translate these promising strategies into effective treatments for DM1-associated cardiac disease. Here, we discuss the current knowledge in DM1 cardiac pathology and preclinical models as well as the benefits and pitfalls of the available therapeutic approaches."

Journal • Review • Cardiovascular • Genetic Disorders • Heart Failure • Muscular Dystrophy • Myotonic Dystrophy • Respiratory Diseases

Targeted strategy by curcumin and tideglusib biomimetic nano-systems alleviates oxidative stress and inflammation under ischemic stroke. (PubMed, Drug Deliv) - "Additionally, Cur@PLTM and Tid@PLTM synergistically scavenged reactive oxygen species (ROS) and promoted the secretion of neuroprotective cytokines via redox and cellular regulatory mechanisms to mitigate ischemia/reperfusion (I/R) injury. Overall, this platelet membrane-biomimetic nanosystem offers a prospective strategy for targeted brain delivery and combined treatment through antioxidative and anti-inflammatory approaches against ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury

Elevated Levels of Active GSK3β in the Blood of Patients with Myotonic Dystrophy Type 1 Correlate with Muscle Weakness. (PubMed, Int J Mol Sci) - "Previously, we described that the small-molecule inhibitor of GSK3β, tideglusib (TG), reduces DM1 pathology in DM1 cell and mouse models by correcting the GSK3β-CUGBP1 pathway, decreasing the mutant CUG-containing RNA...Thrombospondin and TGFβ, linked to the TG-GSK3β pathway in DM1, are also elevated in the DM1 patients' blood. These findings show that the blood levels of active GSK3β might be developed as a potential noninvasive biomarker of muscle weakness in DM1."

Journal • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • GSK3B • TGFB1

The synergistic effect of low-intensity focused ultrasound and tideglusib on odontogenic differentiation of human dental pulp stem cells. (PubMed, Clin Oral Investig) - "This pharmacomechanical approach offers a minimally invasive, biologically driven strategy for regenerative endodontic therapy, with strong translational potential in managing reversible pulpitis and promoting dentine repair."

Journal • Dental Disorders • BCL2L1 • BMP2 • CASP3 • RUNX2

Computational identification of phytochemicals as glycogen synthase kinase 3 beta (GSK3β) inhibitors for therapeutic applications in chronic diseases. (PubMed, Sci Rep) - "ADMET profiling shortlisted 49 compounds, with uzarigenin, jatrophone, chrysin, and podolide exhibiting superior binding affinities compared to Tideglusib (-8.53 kcal/mol)...KEGG pathway analysis highlighted the role of GSK-3β inhibitors in Alzheimer's disease, Wnt signaling, and cancer pathways. This study identifies phytochemicals with potential therapeutic applications for neurodegenerative, cancer, and metabolic diseases, warranting further experimental validation."

Journal • Alzheimer's Disease • CNS Disorders • Diabetes • Metabolic Disorders • Oncology

Injectable GSK3 inhibitor (Tideglusib) hydrogel versus enhanced β-tricalcium phosphate in tibial bone healing (in vitro and in vivo study). (PubMed, Odontology) - "New bone tissue was progressively seen bridging and filling the defects with significantly higher ALP and OPN expression in hydrogel group. Tideglusib hydrogel formulation exhibited superior bone regenerative potential in comparison to beta tricalcium phosphate alloplastic bone substitute."

Journal • Preclinical • SPP1

Advancing Alzheimer's therapeutics via in silico strategies: Tideglusib based multi-target analogues. (PubMed, Comput Biol Chem) - P2 | "SG-09 stands out with the best binding affinity and the stable ligand-protein interaction analogues in the time interval of 100 ns can be used as Multitargeting drug with further in silico, in vitro and in vivo clinical evaluation. This design strategy could thus reap considerable clinical and economic rewards."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Pain • GSK3B

Population Pharmacokinetics of Tideglusib in Congenital and Childhood Myotonic Dystrophy Type 1: Influence of Demographic and Clinical Factors on Systemic Exposure. (PubMed, Pharmaceutics) - "Despite large interindividual variability in the tideglusib concentration vs. time profiles, body weight was the only explanatory covariate for the observed differences. This finding suggests that the use of weight-banded or weight-normalised doses should be considered to ensure comparable exposure across the paediatric population, regardless of age or body weight."

Journal • PK/PD data • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • Pediatrics

Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy. (PubMed, JACC Basic Transl Sci) - "Moreover, TD-treated adult mice displayed a reduction in ventricular arrhythmia following adrenergic stimulation. We provide compelling preclinical data for TD as a potential therapy for patients with ACM."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Heart Failure • DSG2

Towards Mechanism-Based Therapies in Arrhythmogenic Cardiomyopathy. (PubMed, JACC Basic Transl Sci) - No abstract available

Journal • Cardiomyopathy • Cardiovascular

Lithium Restores Inhibitory Function and Neuronal Excitability through GSK-3β Inhibition in a Bipolar Disorder-Associated Ank3 Variant Mouse Model. (PubMed, Neuropharmacology) - "We also show that the selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor Tideglusib recapitulates the enhancement of presynaptic GABAergic signaling. These findings shed new light on how ANK3 variants may contribute to inhibitory deficits in BD and demonstrate that lithium treatment is able to restore these deficits, likely through GSK-3β inhibition. Furthermore, these findings highlight GSK-3β inhibition as a promising therapeutic strategy for treating BD and other neurological disorders affected by GABAergic dysfunction."

Journal • Preclinical • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • ANK3 • GABARAP

Tideglusib: Expanded Access Use in Congenital Myotonic Dystrophy (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: AMO Pharma Limited

New trial • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

Naringenin and SMER28 target lysosomal reformation and rescue SPG11 and SPG15 Hereditary Spastic Paraplegia phenotypes. (PubMed, Pharmacol Res) - "Here we assessed the therapeutic potential of two FDA-approved compounds, tideglusib and naringenin, that target lysosomal function and regeneration, both registered for clinical use. Their effects were compared with those of SMER28 and of miglustat, the latter tested in a phase II clinical trial in SPG11 patients, in both SPG15 and SPG11 patient's derived cells and in the corresponding Drosophila models...Both compounds induced lysosomal tubulation, downstream of mTOR, promoting lysosomal reformation. Our work indicates that lysosomal reformation is a good strategy for HSPs with impaired lysosomal function and identifies naringenin as new modulator of this process, offering further hand to planning phase II clinical trials in SPG11-SPG15 patients."

Journal • Genetic Disorders

Pulp response following direct pulp capping with Tideglusib and mineral trioxide aggregate: an animal study. (PubMed, BMC Oral Health) - "When used as direct vital pulp capping materials in a dog model, Tideglusib causes more soft tissue disorganization and an inflammatory response inside the pulp cavity than ProRoot white MTA."

Clinical • Journal • Inflammation

Evaluation of the effects of tideglusib and calcium sulfate on the healing of experimental bone defects in rabbits. (PubMed, Pol J Vet Sci) - "The study concluded that the combination of tideglusib and calcium sulfate significantly enhanced bone healing compared with the other groups (p<0.005). This suggests that tideglusib, either alone or in combination with bone graft materials, could serve as a promising alternative for the repair of bone defects."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • CNS Disorders • Orthopedics

REACH CDM X: Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy (clinicaltrials.gov) - P2/3 | N=76 | Recruiting | Sponsor: AMO Pharma Limited | Trial completion date: Mar 2025 ➔ Dec 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy

A Selective GSK3β Inhibitor, Tideglusib, Decreases Intermittent Access and Binge Ethanol Self-Administration in C57BL/6J Mice. (PubMed, Addict Biol) - "RNA sequencing analysis of tideglusib actions on ethanol consumption revealed alterations in genes involved in synaptic plasticity and transmission, as well as genes downstream of the canonical Wnt signalling pathway, suggesting tideglusib may modulate ethanol consumption via β-catenin binding to the transcription factors TCF3 and LEF1. The data presented here further implicate GSK3β in alcohol consumption and support the use of tideglusib as a potential therapeutic in the treatment of AUD."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Mood Disorders • Psychiatry • CTNNB1 • TCF3

Bioactive deproteinized bovine bone mineral based on self-assembled albumin nanoparticles promoted bone regeneration via activation of Wnt/β-catenin pathway. (PubMed, Mater Today Bio) - "In this study, we synthesised bovine serum albumin nanoparticles (BNP) loaded with Tideglusib (TD), TD and BNP were bound together by self-assembly, and mixed with deproteinized bovine bone mineral (DBBM) to form a bone substitute material (TD-BNP@DBBM) that had low cytotoxicity, promoted cell proliferation and migration, induced cell differentiation, and regulated osteogenesis...Furthermore, this result suggested a link between the Wnt/β-catenin pathway and the osteogenic effect, providing a basis for subsequent investigations into the mechanism of bone regeneration induced by osteogenic biomaterials. TD-BNP@DBBM might be a promising new approach for treating bone defects."

Journal • Infectious Disease

GSK3B inhibition partially reverses brain ethanol-induced transcriptomic changes in C57BL/6J mice: Expression network co-analysis with human genome-wide association studies. (PubMed, bioRxiv) - "These studies identified discrete networks significantly enriched with genes provisionally associated with AUD, and provide key information on central hubs of such networks. Together these studies document tideglusib as a major modulator of chronic ethanol consumption-evoked brain gene expression signatures, and identify possible new targets for therapeutic modulation of AUD."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Mental Retardation • Psychiatry

Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Hamilton Health Sciences Corporation | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Enrollment open • Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular

Evaluation of the bone regenerative effect of glycogen synthase kinase 3 antagonist Tideglusib carried by different scaffolds on rat calvarial defects. (PubMed, Int J Biol Macromol) - "Within the limits, Tideglusib delivered with a nanocarrier containing PCL/Gel may have favorable impact on bone regeneration. However, the impact may vary with different carrier."

Journal • Preclinical • AXIN2

Tideglusib Enhances ALP Activity and Upregulates RANKL Expression in Osteoblast-Macrophage Co-Cultures within a 3D Collagen Scaffold. (PubMed, J Dent) - "Tx may enhance bone regeneration by modulating inflammatory responses and preserving cell integrity."

Journal • Inflammation • IL1B • TNFA • TNFSF11

Modulation of IRS1 Activity by GSK3β Dictates Insulin Signaling Sensitivity in Podocytes: Implications for Diabetic Kidney Disease (KIDNEY WEEK 2024) - "However, its role in DKD remains elusive. Mouse podocytes were exposed to insulin or a type 2 diabetic milieu, following GSK3β silencing, ectopic expression of a constitutively active GSK3β mutant (S9A), or treatment with tideglusib, an inhibitor of GSK3β... Diabetes-associated GSK3β hyperactivity promotes IRS1 phosphorylation, contributing to desensitization of insulin signaling in podocytes. Therapeutic targeting of GSK3β could re-sensitize insulin signaling in podocytes via regulation of IRS1."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • GSK3B • SLC2A1

Dissection of Key Molecular Events in Podocyte Response to Hyperinsulinemia and Its Implications in Prediabetic Microalbuminuria (KIDNEY WEEK 2024) - "Hyperinsulinemia elicits podocyte injury and microalbuminuria via a series of key molecular events, involving depletion of INSR, desensitization of insulin signaling, and GSK3β hyperactivity, which promotes inhibitory p-IRS1S332 and thereby forms a vicious cycle of insulin signaling resistance and podocyte injury."

Chronic Kidney Disease • Nephrology • Renal Disease • IR