Highlights
- A comprehensive battery that can test all functional domains of the CNS
- Both objective and subjective measures
- Rapid retesting allows researchers to complete several rounds of testing both before and after the drug is administered
- Full dose-effect curves can be measured quickly and easily
- High sensitivity means even subtle effects can be robustly detected
- Highly flexible design, easily adaptable to your specific needs
- Automatic capture of test data with direct entry into a CDISC-validated system
- Proven track record of safety and success in three decades of testing a wide range of CNS drugs
Summary
In the early stages of development of drugs for neurological or psychiatric disorders, one of the most important questions is whether the drug penetrates into the brain and shows pharmacological effects on the central nervous system. The desire to be able to provide an in-depth answer to this question has driven CHDR to develop the NeuroCart.
The NeuroCart is a full battery of neuropsychological and neurophysiological tests that can be used to measure a wide range of CNS functions. Importantly, NeuroCart can be used to correlate a compound’s CNS effects with drug concentration, helping to determine whether or not an effect is specifically due to the compound.
A clear advantage of NeuroCart over other CNS test batteries is that it provides both objective measures (e.g. neurophysiology) and subjective measures (such as cognitive function, memory and mood) of CNS function. What’s more, NeuroCart is completely mobile and self-contained, incorporating all necessary equipment and protocols.
Practical answers to important research questions
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Does our compound have the specific properties that we expect?
CHDR performed the first-in-human trials for a short-acting benzodiazepine. Researchers used a NeuroCart test (saccadic peak velocity) and determined the dose that produced the same effect as a standard dose of midazolam. Pharmacokinetic/pharmacodynamic (PK/PD) analyses showed that the new benzodiazepine was more potent and faster acting than midazolam. Importantly, the predicted optimal dose, potency, and duration of the new compound were subsequently confirmed in clinical studies with patients.
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How do we determine the optimal dose?
Because NeuroCart’s neurophysiological tests can be used as a surrogate marker for measuring a drug’s effect, these tests can be used to identify a dose that has the same effect on CNS function as the effective dose of a known compound. For instance, CHDR recently studied a new neuroleptic D2 receptor antagonist. Using NeuroCart, and the adaptive tracking test in particular, researchers were able to determine a dose with similar potency to an effective dose of haloperidol. Importantly, although previous studies predicted an effective dose of 60 mg, NeuroCart showed that a much lower dose (10-30 mg) is effective. Clinical research in patients later confirmed that a dose as low as 5 mg is effective, and fewer adverse effects were reported at this lower dose compared to 60 mg.
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How do we steer between effect and complications?
In some cases, preclinical research can provide evidence that a promising candidate drug may have a relatively small therapeutic index. This was the case with an ORX1/2 antagonist, a new sleep-inducing medication. Researchers worried that this new drug might induce a narcolepsy-like state, particularly at higher doses. To test this possibility, CHDR used several NeuroCart tests and found that this new compound has promising properties similar to zolpidem and is safe at a dose of 1 mg. These findings were later confirmed in clinical testing.
