IMS-088 / ImStar Therap - LARVOL DELTA

Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS. (PubMed, Biomedicines) - "Here, we tested a new Withaferin-A analog (IMS-088) inhibitor of NF-κB that was found recently to mitigate disease phenotypes in mouse models of familial disease expressing TDP-43 mutant...The effective disease-modifying effects of this drug in a mouse model based on i.c.v. infusion of ALS-CSF suggest that the NF-κB signaling pathway represents a compelling therapeutic target for sporadic ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Metabolic Disorders • Proteinopathy • TARDBP

Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition. (PubMed, Acta Neuropathol Commun) - "The therapeutic effects of inhibiting the pro-inflammatory nuclear factor kappa B (NF-κB) pathway with an analog of Withaferin A, IMS-088, were assessed in symptomatic hFUS mice and were found to improve cognitive and motor function, increase dendritic branches and synapses of motor neurons, and attenuate other ALS/FTD-associated pathological features...Collectively, this work demonstrates that FUSR521G has a cell-autonomous role in causing early pathological changes to dendritic and synaptic structures of motor neurons, and that these changes precede motor defects and other well-known pathological features of ALS/FTD. Finally, these findings provide further support that modulation of the NF-κB pathway in ALS/FTD is an important therapeutic approach to attenuate disease."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Oncology • Sarcoma • Solid Tumor • FUS

Longitudinal study of the neuronal effects of ALS-linked mutant FUS in mice and the therapeutic effects of NF-kB inhibition (ALS-MND 2023) - "Our study shows that dendritic and spine defects that occur in MNs are due to the intrinsic mechanisms caused by FUSR521G. Moreover, these changes are progressive and sufficient to cause behavioral impairments. Importantly, treatment of FUSR521G/Syn1 mice with IMS-088 greatly improves the neuronal morphology and synaptic structures in these mice."

Longitudinal study • Observational data • Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • FUS

Targeting TDP-43 Pathology Alleviates Cognitive and Motor Deficits Caused by Chronic Cerebral Hypoperfusion. (PubMed, Neurotherapeutics) - "Oral administration of a novel analog (IMS-088) of withaferin A, an antagonist of nuclear factor-κB essential modulator (NEMO), led to mitigation of TDP-43 pathology, enhancement of autophagy, and amelioration of cognitive/motor deficits in CCH mice. Taken together, our results suggest that targeting TDP-43 pathogenic inclusions may have a disease-modifying effect in dementia caused by chronic brain hypoperfusion."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • TARDBP

Induction of autophagy mitigates TDP-43 pathology and translational repression of neurofilament mRNAs in mouse models of ALS/FTD. (PubMed, Mol Neurodegener) - "Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies."

Journal • Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Complement-mediated Rare Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • Proteinopathy • NFKB1 • TARDBP