Publications

MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer’s Disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid β plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD.

GNUV205, an Engineered IL-2 Variant Fused with a Novel Anti-PD-1, Potently Regresses Tumor Growth without Toxicity via Selective Targeting to PD-1+ Teff Cells in Tumor Microenvironments

GNUV205 was designed to overcome these limitations by fusion of the TME-selective anti-PD-1 and eIL-2 selective for IL-2Rβγ-expressing Teff cells via our proprietary heterodimeric Fc platform technology.

2021 SfN_MEK1/2 inhibition rescues neurodegeneration by activation of autophagic lysosomal function in Alzheimer’s Disease

We report that administration of trametinib, a MEK1/2 specific inhibitor, ameliorates memory deficits and synaptic dysfunction and reduces Aβ deposition in various Alzheimer’s disease models. The mechanism of neuroprotection by trametinib is achieved through an enhancement of protective autophagy, a conserved cellular process for clearing dysfunctional organelles and protein aggregates. Thus, we demonstrate that trametinib contributes to the recovery of damaged neuronal functions, representing a potential treatment for Alzheimer’s disease. .

2021 SfN_Trametinib restores memory deficits by activating endogenous neurogenesis in mouse model of Alzheimer’s disease

Repairing damaged neural tissues in patient’s brain is a plausible therapeutic approach for Alzheimer’s disease (AD) and other neurodegenerative diseases. In this study, we report that inhibition of Mitogen-activated protein kinase (Extracellular Receptor Kinase) signaling by trametinib induces generation of new neurons from endogenous neural stem cells in the brain regions affected by the disease and recovers cognitive functions of AD model animals. We propose that trametinib is a promising therapeutic candidate for Alzheimer’s disease.

2021 SfN_Trametinib protects motor neurons from degeneration by enhancing autophagy in the SOD1-G93A amyotrophic lateral sclerosis model mice

Administration of trametinib, a MEK1/2 specific inhibitor, is shown to improve survival and motor functions of the Amyotrophic lateral sclerosis (ALS) model animals. Enhancement of neuroprotective autophagy is the mechanism of trametinib’s therapeutic effects for ALS. Trametinib is currently in clinical trial (Phase I/IIa) for the indication of ALS in Korea (NCT04326283).

Trametinib Protects Motor Neurons from Degeneration by Enhancing Autophagy in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis

Genuv presented three posters at the Keystone Virtual Symposium “Neurodegenerative Disease: Genes, Mechanisms and Therapeutics,” that show promising preclinical results for our new drug candidate, SNR1611. In mouse models of amyotrophic lateral sclerosis (Lou Gehrig’s Disease), SNR1611 showed positive neurogenesis and neuroprotective effects. The studies are an important validation of our ATRIVIEW® platform, which screens for compounds that induce differentiation of neurons without neuronal cell death in simulated disease conditions.

MEK1/2 Inhibition Rescues Neurodegeneration in Alzheimer’s Disease Models by Enhancing Autophagy

Genuv presented three posters at the Keystone Virtual Symposium “Neurodegenerative Disease: Genes, Mechanisms and Therapeutics,” that show promising preclinical results for our new drug candidate, SNR1611. In mouse models of Alzheimer’s Disease, SNR1611 showed positive neurogenesis and neuroprotective effects. In one of the studies of a mouse model of Alzheimer’s, orally administered drug led to reduced beta amyloid plaque deposits and recovery of impaired neuronal structures and cognitive functions. The studies are an important validation of our ATRIVIEW® platform, which screens for compounds that induce differentiation of neurons without neuronal cell death in simulated disease conditions.

MEK1/2 Inhibition by Trametinib Rescues Memory Deficits via Activation of Adult Neurogenesis in Alzheimer’s Disease Mice

Genuv presented three posters at the Keystone Virtual Symposium “Neurodegenerative Disease: Genes, Mechanisms and Therapeutics,” that show promising preclinical results for our new drug candidate, SNR1611. In mouse models of Alzheimer’s Disease, SNR1611 showed positive neurogenesis and neuroprotective effects. In one of the studies of a mouse model of Alzheimer’s, orally administered drug led to reduced beta amyloid plaque deposits and recovery of impaired neuronal structures and cognitive functions. The studies are an important validation of our ATRIVIEW® platform, which screens for compounds that induce differentiation of neurons without neuronal cell death in simulated disease conditions.