Translational Science

Research on patients and human tissues has contributed greatly to our knowledge of CNS pathology, but clinical studies of novel treatments are appropriately ethically constrained and are confounded by the inability to experimentally control necessary variables.

While rodent models remain widely deployed, there are limitations to the resulting data, including data from genetic models given that monogenetic causes of CNS pathology are less common than the prevalent polygenetic conditions.

For CNS translational evaluation the use of nonhuman primates such as the green monkey has distinct advantages.

They share greater homology to humans in genomics, pharmacokinetics, pharmacodynamics neurophysiology, neurochemistry, endocrinology, immunology, neuronal network complexity, behavioral specializations, cognitive processing, and synaptic regulation in addition to the organization and function of the hippocampus, prefrontal cortex, and other regions relevant to important disease such as Alzheimer’s, Parkinson’s and schizophrenia.

Virscio applies deep neuroscience expertise and methodological capabilities to healthy and disease relevant CNS test systems to address critical translational objectives. 

The green monkey eye is over half the size of the human eye, with proportionate ratios of neuroretina, vitreous chamber, lens and anterior chamber volumes, and very similar aqueous production and outflow dynamics. This closely shared anatomy includes the presence of a macula, which defines humans and primates as a highly visual species, allowing modeling of macular degeneration and other diseases of the central retina not possible in non-primates.

A similarly closely shared microvascular anatomy of the optic nerve and the presence of a lamina cribrosa, elevates sensitivity to occlusion and compression of the vessels and retinal ganglion axons channeling through the optic nerve, allowing uniquely predictive modeling of human glaucoma and optic neuropathies.

Enabled by this homology, we have validated the green monkey and a variety of disease models as test systems for screening ophthalmic therapeutics for multiple indications.

To maximize the value of study data, Virscio applies human clinical ophthalmic instrumentation and clinical endpoints to enhance success of clinical translation.

With age, African green monkeys and other nonhuman primates exhibit spontaneous obesity, dyslipidemia, and insulin resistance with end organ manifestations. Green monkeys also respond to sustained high fat, high caloric diets to develop accelerated obesity, insulin resistance, dyslipidemia, pancreatic pathology, and atherosclerosis.

Many of the physiological factors that predispose humans to metabolic syndromes, including fluctuating hormone levels, menopause, stress, and early life caloric exposure, also predispose green monkeys and are incompletely modeled in lower species.

Likewise, green monkeys respond to disruptions in renin-angiotensin regulation of blood pressure or induced cardiac outflow obstructions with elevations in blood pressure and cardiac remodeling to develop congestive heart failure.

Virscio accesses a diverse demographic to select animals with natural or induced cardiometabolic phenotypes to screen candidate interventions, applying glucose tolerance testing, biomarker profiling, body composition scanning, echocardiography, cardiac telemetry and other translational endpoints.  

Non-primate models, particularly small animal species, can be efficient and cost-effective, but they often lack the genetic, anatomical, biochemical, or immunologic features needed to reliably predict human biodistribution, safety, and therapeutic effect.

For gene and cell therapies, where vector binding, transgene delivery, and therapeutic cell integration depend on specific cellular properties, close genetic and immunologic alignment between the test species and humans is especially important. Nonhuman primates are critical to closing this translational gap.

Well established and tolerated immunosuppression protocols enable modeling of immunomodulation regimens for clinical gene and cell interventions, and application of green monkeys for cell xenograft testing and modeling.

The St. Kitts green monkey is of specific value to gene therapy testing with a historic isolation from common viruses employed as gene vectors and low prevalence of neutralizing antibodies to commonly used vector capsids.

Coupled with Virscio’s broad gene and cell therapy experience, our primate test systems allow definition of safe and effective vector and cell delivery methods, biodistribution, immune response, cell-specific transgene expression and cell viability, all of which are critical determinants of clinical efficacy and safety. 

Standard Routes of Administration

We routinely implement intravascular, intraparenchymal, intrathecal, intramuscular, intra-articular, intravitreal, subretinal, and other clinically relevant routes of administration to support translational objectives.

Effective assessment of target engagement for protein and RNA therapeutics depends on the specific target sequences and their resulting structures, with overall pharmacodynamic and safety profiles further driven by the biology of the affected pathways.

The degree to which these sequence-defined targets and associated cellular and tissue physiology are conserved between species determines how well a model can predict human outcomes.  Accordingly, nonhuman primates remain a critical test system for monoclonal antibodies, peptides, hormone and vaccine therapies, and mRNA, siRNA, and antisense oligonucleotide (ASO) candidates.

Virscio leverages deep experience in targeted delivery of protein and RNA therapeutics and in optimized endpoint assessment to evaluate safety and efficacy in biologically relevant nonhuman primate models. Whether dosing is single, repeat, or sustained release; systemic, intrathecal, or via other routes; or focused on specific clinical age groups, Virscio is equipped to design and execute robust preclinical studies that closely model intended clinical use and support precision medicine objectives.

Like humans, African green monkeys develop signs of physical decline and age-associated diseases that do not occur in lower species.

With access to a broad age range of green monkeys, Virscio has established epigenetic, proteomic, and functional biomarkers such as gait and muscle strength testing that correlate to human clinical findings and complement traditional safety and physiologic evaluations to enrich interpretation of aging biology and age modifying interventions.

These age-related endpoints, and unique access to older animals enable testing of safety and efficacy to provide rationale for clinical trial. Access to younger animals additionally allows aging biology insights and evaluation of interventions for pediatric indications.