Restoring synaptic plasticity
ENCUE's compounds induce plasticity in primary cortical neuronal cultures.
Our proprietary EEG quantitative biomarker allows us to measure compound efficacy, optimize patient selection, and monitor disease progression.
Our lead compound, NQ-013, induces structural plasticity.
Healthy synapses make a healthy brain
Our discovery program targets synaptic plasticity dysfunction; synaptic plasticity is fundamental for all brain
functions.
ENCUE developed a unique platform to assess synaptic plasticity with clinical relevance using genetic and non-genetic animal models to assess the effect of our compounds on cognition including:
- Normal adult rats, Autistic mice (Shank), Mice with Alzheimer’s disease (5XFAD), Aged rats with cognitive deficits, Rats with Traumatic Brain Injury (TBI), and Rats exposed to Chronic Stress (CUS)
- Neuro-anatomical assessments of spine formation
- Pharmacological assessment increases in synaptic AMPR expression
- In vivo and ex vivo elecro-physiological studies
Our proprietary platform technology allows us to create novel receptor modulators that are fully synthetic and orally deliverable.
ENCUE’s compounds have been shown to restore and enhance cognitive function.
Why has ENCUE created an Insulin-Like Growth Factor Binding Protein 2 (IGFBP2) mimetic small molecule program?
IGFBP2 can mimic IGF growth factor functions in the brain, including modulation of neurogenesis, enhancing synaptic function, and facilitating cognition
IGFBP2
- Chaperones IGF1 and IGF2
- Readily crosses the BBB
- It is synthesized by astrocytes and neurons
- Increases spine formation,
- Increases myelin formation,
- Enhances NMDAR and AMPAR activity,
- Modulates transcription and translation
ENCUE’s lead compound NQ-013 is an IGFBP2 mimetic with similar but many distinctive CNS modulatoryproperties
NQ-013
- Readily crosses the Blood-Brain Barrier
- Competes with IGFBP2 at a novel binding domain on the IGF2R
- Does not chaperone growth factors to growth factor receptors
- Binds directly to dendritic spines
- Activates the MEK/ERK pathway
- Increases the expression of IGF2, NMDA and AMPA receptors
- Increases excitatory field potentials
- Enhances learning and memory
- Reverses cognitive deficits in models of Autism, Alzheimer’s disease, and Traumatic Brain Injury
Relevant Patents and Publications
- Insulin like growth factor binding protein bioactive peptide fragments, US20220144896A1. See More
- System and method for detecting an emotional state, 63/450,502.
- Compounds and Methods for Treating Central Nervous System Disorders. Prov. 63/536,009.
- Uncovering the molecular basis of positive affect using rough-and-tumble play in rats: a role for insulin-like growth factor 1. Neuroscience (2010). See More
- Insulin-Like Growth Factor 1 Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus. Int. J. Neuropsychopharmacol (2015). See More
- IGFBP2 Produces Rapid-Acting and Long-Lasting Effects in Rat Models of Posttraumatic Stress Disorder via a Novel Mechanism Associated with Structural Plasticity. Int. J. Neuropsychopharmacol (2017). See More
- An IGFBP2-derived peptide promotes neuroplasticity and rescues deficits in a mouse model of Phelan-McDermid syndrome. Molecular Psychiatry (2023). See More
- A prefrontal cortex alpha/delta switch controls the transition from positive to negative affective states. Nature Discover Mental Health (In press). See More