SM07883 / Biosplice Therap - LARVOL DELTA

Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury. (PubMed, Neurotherapeutics) - "Transgenic mice expressing human Tau (hTau) were subjected to repetitive head injury (RHI) over a 3-month period and treated with either vehicle or SM07883, a potent, brain-penetrant DYRK1A inhibitor...These behavioral improvements were accompanied by significant reductions in RHI-induced pTau accumulation within the midbrain and brainstem, along with decreased astroglial and microglial activation in the corpus callosum, brainstem, and cortical regions beneath the injury site. Collectively, these findings demonstrate that DYRK1A inhibition mitigates tau pathology and chronic neuroinflammation following repetitive injury, supporting DYRK1A as a promising therapeutic target for the long-term neurological consequences of TBI."

Journal • CNS Disorders • Inflammation • Vascular Neurology

Dyrk1a inhibition reduced tau hyperphosphorylation, neuroinflammation and improved locomotor function, in a mouse model of repeat mild traumatic brain injury (Neuroscience 2022) - "Transgenic mice expressing human tau (hTau) were subjected to r-mTBI weekly over a period of 3 months and treated with either vehicle or the potent and selective brain-penetrant DYRK1A inhibitor SM07883 (3 mg/kg by daily gavage for 5 months)...However, no treatment effect on learning or spatial memory was reported using the Barnes or Elevated Plus Maze neurobehavioral tests. These data demonstrated that DYRK1A inhibition reduced chronic neuroinflammation, pTau accumulation and restored the locomotor deficits related to repetitive mild traumatic brain injury in this context."

Preclinical • CNS Disorders • Vascular Neurology

Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer's disease. (PubMed, Aging Cell) - "SM07883, a potent, orally bioavailable, brain-penetrant DYRK1A inhibitor, significantly reduced effects of pathological tau overexpression and neuroinflammation, while functional endpoints were improved compared to vehicle in animal models. This small molecule has potential as a treatment for AD."

Journal • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation

[VIRTUAL] SM07883, A NOVEL, POTENT, AND SELECTIVE ORAL DYRK1A INHIBITOR, REDUCES NEUROINFLAMMATORY RESPONSES IN MOUSE MODELS (AAT-ADPD 2020) - "Conclusions SM07883 potently reduced glial activation and inflammatory mediator production in preclinical models. SM07883 represents a potential treatment for neurodegenerative disorders; a clinical trial is ongoing."

Preclinical

Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor (Neuroscience 2019) - "Motor function in the wire hanging test was significantly improved in SM07883-treated JNPL3 mice compared to vehicle (p=0.048).SM07883, a selective, potent, and oral DYRK1A inhibitor currently being tested in a clinical trial, significantly reduced tau phosphorylation, pathological tau overexpression and associated neuroinflammation, and improved functional endpoints compared to vehicle. SM07883 has potential as a treatment for chronic tauopathies such as AD."

Anti-inflammatory effects of SM07883, a novel, potent, and selective oral DYRK1A inhibitor in mouse models of neuroinflammation (Neuroscience 2019) - "SM07883, an oral DYRK1A inhibitor, significantly reduced proinflammatory mediators and associated inflammation in both innate and adaptive inflammatory mouse models compared to vehicle. SM07883 may potentially modulate neuroinflammation in neurodegenerative diseases."

Preclinical

SM07883, a novel, oral DYRK1A inhibitor, improves cognition and protects against amyloid and tau pathologies in the 3xTg-AD mouse model of Alzheimer's disease (Neuroscience 2019) - "Immunostaining showed amyloid and tau pathology reduction in the hippocampal area while GFAP and Iba-1 showed reduced gliosis, which was associated with a reduction in proinflammatory cytokines. SM07883-treated mice performed better in NOR and SM07883 prevented cognitive deficit in the Y-maze.In two independent studies in triple-transgenic mice, daily oral administration of SM07883, a DYRK1A inhibitor, showed reduction of pathological AD hallmarks (tau and amyloid), associated neuroinflammation, and protected against cognitive deficits compared to vehicle."

Preclinical

Anti-Inflammatory Effects of SM07883, a Novel, Potent, and Selective Oral DYRK1A Inhibitor in Neurodegenerative Mouse Models (AAIC 2019) - "SM07883, an oral DYRK1A inhibitor, significantly reduced proinflammatory mediators and associated inflammation in neurodegenerative models vs. vehicle. SM07883 may potentially modulate neuroinflammation in neurodegenerative diseases and has entered a clinical trial."

Preclinical

Samumed Announces Publication of Preclinical Data Demonstrating That SM07883 is a Potential Treatment for Alzheimer’s Disease (GlobeNewswire, Samumed) - Samumed, LLC, announced today the publication of preclinical data demonstrating that SM07883 inhibits tau pathology and associated neuroinflammation, both of which are implicated in Alzheimer’s disease. The article titled “Tau pathology reduction with SM07883, a novel, potent, and selective oral DYRK1A inhibitor: A potential therapeutic for Alzheimer’s disease” has been published in Aging Cell.

Preclinical

Samumed Doses First Subject in Phase 1 Trial of SM07883, a Potential Treatment for Alzheimer’s Disease (GlobeNewswire, Samumed) - Samumed, LLC, announced today that it has dosed the first subject in its phase 1 trial of SM07883, a potential treatment for Alzheimer’s disease (AD). SM07883 is a novel, oral, small-molecule designed to reduce disease pathology by selectively inhibiting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).

Clinical • Trial status