Sonsuvi (brimapitide) / Kuste Biopharma, Altamira Therap - LARVOL DELTA

Brimapitide (BRM), potential novel treatment for bladder pain syndrome (BPS/IC), is safe and well tolerated. Report from a phase 1/2a study (EAU 2024) - No abstract available

P1/2 data • Interstitial Cystitis • Musculoskeletal Pain • Pain

Bladder pain syndrome AKA interstitial cystitis - a condition with severe unmet medical need: an exploration of brimapitide as a potential treatment opportunity. (PubMed, Curr Opin Urol) - "In a phase 1/2a exploratory trial, intravesical instillation of brimapitide confirmed local action while eliciting in minimal systemic exposure, resulting in a promising and favorable safety profile. Efficacy exploration suggests that brimapitide reduces pain, improves signs and symptoms of IC/BPS and improves the general wellbeing of the study participants."

Journal • Interstitial Cystitis • Musculoskeletal Pain • Pain

First record of Cladosporium oxysporum as a potential novel fungal hyperparasite of Melampsora medusae f. sp. deltoidae and screening of Populus deltoides clones against leaf rust. (PubMed, 3 Biotech) - "Alternatively, by screening 25 high-yielding clones of P. deltoides, five clones (FRI-FS-83, FRI-FS-92, FRI-FS-140, FRI-AM-111, and D-121) were enlisted under highly resistant category...Combining this biocontrol approach with the use of resistant host germplasm could be an environment friendly strategy for preventing foliar rust and increasing poplar productivity in northern India. The online version contains supplementary material available at 10.1007/s13205-023-03623-x."

Journal

The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells. (PubMed, Front Mol Neurosci) - "D-JNKI-1 decreased neomycin-induced ROS generation, reduced caspase-8 and cleavage of caspase-3 expression, sustained JNK activation and AMPK and p38 phosphorylation, downregulated Bax, and upregulated Bcl-2. Together, D-JNKI-1 plays an essential role in protecting against neomycin-induced HEI-OC1 cell apoptosis by suppressing ROS generation, which inhibited JNK activation and AMPK and p38 phosphorylation to ameliorate JNK-mediated HEI-OC1 cell apoptosis."

IO biomarker • Journal • BCL2 • CASP3 • CASP8 • MAPK8

JNK signaling provides a novel therapeutic target for Rett syndrome. (PubMed, BMC Biol) - "As a summary, we found altered JNK signaling in models of RTT and suggest that D-JNKI1 treatment prevents clinical symptoms, with coherent results at the cellular, molecular, and functional levels. This is the first proof of concept that JNK plays a key role in RTT and its specific inhibition offers a new and potential therapeutic tool to tackle RTT."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Gene Therapies • Movement Disorders • Psychiatry • MAPK8

c-Jun N-terminal kinase 1 (JNK1) modulates oligodendrocyte progenitor cell architecture, proliferation and myelination. (PubMed, Sci Rep) - "Moreover, JNK1 KO and WT D-JNKI-1 treated OLs, while not showing overt alterations of differentiation in vitro, display a reduced surface compared to controls. Our results unveil a novel player in the complex regulation of OPC biology, on the one hand showing that JNK1 ablation cell-autonomously determines alterations of OPC proliferation and branching architecture and, on the other hand, suggesting that JNK1 signaling in OLs participates in myelination in vivo."

Journal • Solid Tumor • MAPK8

Posttranslational modifications as therapeutic targets for intestinal disorders. (PubMed, Pharmacol Res) - "Posttranslational modifications can be common denominators, as well as distinct biomarkers, characterizing pathological differences of various intestinal diseases. This review provides experimental evidence that identifies changes in posttranslational modifications from patient samples, primary cells, or cell lines in intestinal disorders, and a summary of carefully selected information on the use of pharmacological modulators of protein modifications as therapeutic options."

Journal • Review • Celiac Disease • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Solid Tumor • Targeted Protein Degradation

HEALOS: AM-111 in the Treatment of Acute Inner Ear Hearing Loss (clinicaltrials.gov) - P3; N=256; Active, not recruiting; Sponsor: Auris Medical AG; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar

Inhibition of Vascular c-Jun N-Terminal Kinase 2 Improves Obesity-Induced Endothelial Dysfunction After Roux-en-Y Gastric Bypass. (PubMed, J Am Heart Assoc) - "Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity-induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity."

Journal • Biosimilar • Cardiovascular • Diabetes • Metabolic Disorders • Obesity

Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes. (PubMed) - Neurosci Bull - "These modulators were the microglial inhibitors minocycline and ZVEID (a caspase-6 inhibitor) and the astroglial inhibitors L-α-aminoadipate (L-AA, an astroglial toxin) and carbenoxolone (a connexin 43 inhibitor), as well as U0126 (an ERK kinase inhibitor) and D-JNKI-1 (a c-Jun N-terminal kinase inhibitor). Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain."

Journal • Biosimilar • CNS Disorders • Demo Pain • Oncology • Pain • Solid Tumor

Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study. (PubMed, Otol Neurotol) - "AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts."

Clinical • Journal • P3 data

JNK signaling activation in the Ube3a maternal deficient mouse model: Its specific inhibition prevents post-synaptic protein-enriched fraction alterations and cognitive deficits in Angelman Syndrome model. (PubMed, Neurobiol Dis) - "To study JNK's role in Ube3a pathology we treated mice with the specific JNK inhibitor peptide, D-JNKI1, from 7 to 23 weeks of age...In particular, it was clear that JNK is a key player in regulating AS synaptic alterations and the correlated cognitive impairments, in fact, its specific inhibition tackles Ube3a pathology. This study sheds new light on the neuronal functions of UBE3A and offers new prospects for understanding the pathogenesis of UBE3A-related disorders."

Journal • Preclinical • MAPK8

Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111). (PubMed, Hear Res) - "Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea."

Journal • Review

A novel nanoparticle delivery system for targeted therapy of noise-induced hearing loss. (PubMed, J Control Release) - "When compared to untargeted nanoparticles, the delivery of a c-Jun N-terminal kinase (JNK) inhibitor, D-JNKi-1, to OHCs by targeted nanoparticles improved protection from noise induced hearing loss (NIHL). This is the first demonstration of a protection from NIHL using a novel safe and controllable delivery system which is minimally-invasive to the inner ear and, as such, is an extremely appealing technique for use in many clinical applications."

Journal

Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study. (PubMed, Otol Neurotol) - "AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4."

Clinical • Journal • P3 data