Schizophrenia
Schizophrenia is a complex neuropsychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment, each representing important therapeutic challenges. Successful development of novel treatments requires preclinical models that capture these distinct disease domains while providing translational relevance to the clinic.
Transpharmation offers a comprehensive portfolio of electrophysiology, behavioral, cognitive, and pharmacological models to support the discovery and development of innovative therapeutics for schizophrenia. Our integrated approach enables assessment of neural circuitry, sensory processing, cognition, motivation, social behavior, and disease-relevant biomarkers within a single development program.
Models and assessments
Abnormal sensory processing and disrupted cortical network activity are hallmark features of schizophrenia. Our platform evaluates clinically relevant biomarkers that bridge preclinical and clinical research, including:
- Auditory Event-Related Potentials (ERP)
- Mismatch Negativity (MMN)-like responses
- Auditory Steady-State Response (ASSR)
- Gamma-band oscillations
- Pre-pulse Inhibition (PPI)
These endpoints can be assessed using standard and oddball paradigms and evaluated in established translational pharmacological models.
Negative symptoms, including flat affect, anhedonia and lack of motivation, diminished reward responsiveness, and social withdrawal, significantly contribute to disability and poor quality of life.
Transpharmation offers behavioral approaches to assess negative symptom domains, including:
- Progressive Ratio schedules for motivation and reward processing
- Social Interaction paradigms
- Additional behavioral assays tailored to specific therapeutic mechanisms.
These models support identification of treatments aimed at improving functional outcomes beyond symptom control.
Cognitive deficits are among the strongest predictors of long-term functional outcomes in patients with schizophrenia and remain a major unmet medical need. Our cognitive testing capabilities assess key domains relevant to clinical dysfunction, including:
- Attention
- Working memory
- Executive function
- Cognitive flexibility
- Recognition memory
Available assays include:
- 5-Choice Serial Reaction Time Task (5-CSRTT)
- Delayed Matching-to-Position (DMTP)
- Novel Object Recognition (NOR)
- Reversal Learning
These models align with clinically relevant cognitive domains and support evaluation of compounds targeting cognitive impairment associated with schizophrenia.
Our portfolio includes established pharmacologically induced models of glutamatergic, dopaminergic, cholinergic, and serotonergic dysfunction, which enable investigation of disease mechanisms and therapeutic interventions across multiple pathways implicated in schizophrenia. These include:
- PCP models (acute and subchronic)
- Ketamine challenge models
- MK-801 models
- Amphetamine-induced hyperactivity models
These can be combined with electrophysiological, cognitive, and behavioral endpoints to provide a comprehensive assessment of compound efficacy and mechanism of action.
To support target validation and mechanistic research, we offer a range of disease-relevant models, including:
- DISC1
- ARTE10
- Additional transgenic and genetically modified rodent models when appropriate
Why Transpharmation?
- Integrated electrophysiology, behavioral, and cognitive capabilities
- Translational biomarkers with clinical relevance
- Expertise in positive, negative, and cognitive symptom domains
- Flexible study designs tailored to novel mechanisms of action
- Comprehensive support from target validation through preclinical development
Platforms used in this area
Electroencephalography (EEG) In-vivo rodent telemetry
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Cognitive Assessment Aged-dog memory and cognitive decline
Transgenics Genetically modified mice
Partner with our scientists.
Whether your program focuses on psychosis, cognitive impairment, negative symptoms, or novel disease mechanisms, our team can design a customized strategy that aligns with your scientific objectives and development goals.