ET-101 / Eikonoklastes Therap, UC San Diego Health - LARVOL DELTA

i.c.v. delivery of AAV9-synapsin-promoted caveolin-1 attenuates neuromuscular deficits and neuromuscular degeneration in hSOD1G93A mice. (PubMed, Mol Ther Adv) - "These findings serve as preclinical proof of concept that i.c.v. delivery of AAV9-SynCav1 can achieve CNS target engagement and produce selective functional and anatomical benefits in hSOD1G93A mice."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • CAV1

Systemic delivery of synapsin-promoted caveolin-1 overexpression ameliorates pathological TDP-43-induced cognitive decline and neurodegenerative changes. (PubMed, Alzheimers Dement) - "These findings establish a novel link between TDP-43 proteinopathy and MLR instability, supporting SynCav1 as a "neuron-centric" candidate for treating TDP-43-related neurodegeneration."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Proteinopathy • CAV1 • GRIN2A • TARDBP

Efficacy and Safety of Mobile App-Based Metamemory Cognitive Training for Mild Cognitive Impairment: Multicenter Randomized Clinical Trial. (PubMed, JMIR Mhealth Uhealth) - P=N/A | "ET-101 significantly improved cognitive function compared to the sham device, with effects observed not only in the memory domain but also in the language domain, indicating a transfer effect. Therefore, ET-101 has the potential to provide effective MMT to a broader population with MCI by overcoming location and personnel limitations through a mobile app-based platform."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Intracerebroventricular administration of AAV9-synapsin caveolin-1 has the potential broader benefit for the treatment of amyotrophic lateral sclerosis mice model (ALS-MND 2025) - "Grip strength significantly increased in treated males and trended upward in females (ρ = 0.0415, 0.2624, respectively, Student's t-test). MEP amplitude showed a non-significant increase in males and significant improvement in females (ρ = 0.1093, 0.0392, Student's t-test). On WB, the Cav-1/GAPDH value in the treatment group was significantly increased by 16.3 times in male and 6.73 times in female of the motor cortex (ρ = 0.025, 0.004, respectively, Student's t-test), by 4.43 times in male and 4.1 times in female of the cervical spinal cord of males (ρ = 0.0018,0.0075, respectively Student's t-test), and by 2.05 times in males and 2.5 times in females of the lumbar spinal cord (ρ = 0.0007,0.002, respectively, Student's t-test)."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • CAV1 • GAPDH • NTRK2 • SOD1

Neuronal targeted Caveolin-1 overexpression preserves mitochondrial integrity and cognitive function in a TDP-43 mouse model of ALS/FTD (ALS-MND 2025) - "Our study has demonstrated that overexpression of neuronal Cav-1 via systemically delivered PhP.eB-SynCav1 provides a robust pro-cognitive effect in hippocampal-dependent memory. Ultrastructural analysis revealed that SynCav1 preserved synapse number, maintained the integrity of myelinated axons, and mitigated mitochondrial hyperfragmentation. Furthermore, IB of the hippocampal tissue showed that SynCav1 restored the balance in mitochondrial dynamics by suppressing excessive mitochondrial fission signaling in the hippocampus of TDP-43A315T mice."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Mood Disorders • Psychiatry • CAV1 • TARDBP

Neuron-targeted caveolin-1 overexpression attenuates cognitive loss and pathological transcriptome changes in symptomatic Alzheimer's disease models. (PubMed, Signal Transduct Target Ther) - "Subcellular membrane fractionation revealed that SynCav1 preserved MLR-localized pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R), a well-known regulator of ADNP expression. Together, these findings highlight SynCav1 as a unique and promising gene therapy candidate in the treatment of AD."

Journal • Alzheimer's Disease • CNS Disorders • Gene Therapies • ADCYAP1 • ADNP • CAV1

AAV-SynCav1 Administration to the Hippocampus of Cuprizone Mouse Model of Multiple Sclerosis Preserves Hippocampal Myelination (ASGCT 2025) - "Cuprizone diet for 6 weeks induces prominent hippocampal demyelination and resultant fear memory deficits. Direct hippocampal gene delivery of SynCav1 preserved hippocampal myelin in cuprizone mice, suggesting that SynCav1 may be an effective gene therapy to mitigate neurodegeneration in MS. Disease Focus of Abstract:Central Nervous System Disorders"

Preclinical • Alzheimer's Disease • CNS Disorders • Gene Therapies • Multiple Sclerosis • CA3 • CAV1

Halotolerant PGPB Staphylococcus sciuri ET101 protects photosynthesis through activation of redox dissipation pathways in Lycopersicon esculentum. (PubMed, Plant Physiol Biochem) - "The genes involved in photorespiratory process, cyclic electron flow (CEF), and alternative oxidase (AOX) pathway of mitochondrial respiration were abundantly expressed in leaves of ET101 inoculated plants indicating their involvement in protecting photosynthesis from salt stress induced photoinhibition. Collectively, our results indicated that S. sciuri ET101 has the potential in protecting photosynthesis of tomato plants under salinity stress through activation of redox dissipation pathways."

Journal

DREAM: Digital Therapeutics Research on Efficiency About Mild Cognitive Impairment Study (clinicaltrials.gov) - P=N/A | N=100 | Active, not recruiting | Sponsor: Emocog Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Jun 2024

Enrollment closed • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

DREAM: Digital Therapeutics Research on Efficiency About Mild Cognitive Impairment Study (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Emocog Inc.

New trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Eikonoklastes Therapeutics Receives FDA Orphan Drug Designation for 1st-in-class Treatment of Amyotrophic Lateral Sclerosis (ALS) (Businesswire) - “Eikonoklastes Therapeutics...announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for the ET-101 program….‘The FDA’s Orphan Drug Designation for ET-101 reflects the compelling data underlying the ET-101 program and its potential as a 1st-in-class treatment option for both familial and sporadic ALS…Achieving Orphan Drug Designation is an important regulatory milestone that further validates our efforts to efficiently develop ET-101. We look forward to rapidly advancing this novel technology towards our First-in-Human clinical trial.’”

Orphan drug • Amyotrophic Lateral Sclerosis • CNS Disorders