Small molecule inhibitor of cognitive impairment associated with neurodegenerative disease

This technology is an analog of the retired clinical psychotropic drug minaprine for the treatment of cognitive or behavioral disorders associated with neurodegenerative disorders.

Unmet Need: Treatment for cognitive impairment caused by neurodegenerative diseases

Neurodegenerative diseases are associated with progressive deterioration of brain regions that are essential for cognitive and behavioral functioning. Currently, neurodegenerative diseases lack treatments for neuropsychiatric symptoms, particularly for diseases such as Alzheimer’s disease. Furthermore, current treatments primarily involve the use of atypical antipsychotics and antidepressants, which are associated with side effects that have limited their use. Identifying and developing small molecule inhibitors can assist in treating neurodegenerative diseases specifically by reducing behavioral and cognitive dysfunction and associated neuropsychiatric symptoms such as anxiety and/or depression.

The Technology: Small molecule inhibitor for reduction of neurodegeneration-associated cognitive dysfunction

This technology identifies an analog of the retired clinical psychotropic drug minaprine—without its pharmacogenetic liability—for the treatment of cognitive or behavioral issues stemming from neurodegenerative disorders. The technology enhances serotonin receptor 2B antagonism and has been shown to reduce behavioral and synaptic dysfunction in animal models of Alzheimer’s disease. The technology can ameliorate the breakdown of communication between neurons, known as synaptic dysfunction, a key contributor to the dysregulation of cell communication that manifests as cognitive or behavioral impairment associated with neurodegenerative disorders such as Alzheimer’s disease, Alzheimer’s disease-related dementia, and other dementias.

This technology has been validated in mouse models of Alzheimer’s disease.

Applications:

  • Treat synaptic and behavioral dysfunction associated with Alzheimer’s disease
  • Treatment of neuropsychiatric, cognitive, or behavioral disorders associated with neurodegenerative disorders
  • Treatment for tauopathies, Alzheimer’s disease-related dementia, and other dementias

Advantages:

  • Does not have the pharmacogenetic liability of minaprine
  • Beneficial effect on the long-term potentiation defects
  • Protects against the impairment of spatial memory loss, as shown in models of amyloid-beta and tau elevation
  • Can be used in combination with other treatments

Lead Inventor:

Ottavio Arancio, M.D., Ph.D.

Patent Information:

Patent Pending (WO/2024/148148)

Related Publications:

Tech Ventures Reference:

Quick Facts:
Tags
5-HT receptor5-HT2B receptorAmyloid betaAttenuationAtypical antipsychoticCell signalingCognitive deficitDementiaLong-term potentiationMonoamine oxidase inhibitorNeurodegenerative diseaseNeuropsychiatryPsychoactive drugSmall moleculeSpatial memoryStructural analog
Inventors
Daniel M. WattersonErica AcquaroneOttavio ArancioSaktimayee Mitra Roy
Manager
Jerry Kokoshka
Departments
PathologyPharmacologyTaub Institute
Divisions
Columbia University Medical Center (CUMC)Feinberg School of Medicine
Reference Number
CU23096
Release Date
2025-04-10