Products such as cytotoxic chemotherapeutics and AAV-based gene therapies are associated with gangliotoxicity. Despite this, prior toxicology guidance provided no recommendations for which sensory and autonomic ganglia to evaluate in nonclinical general toxicity studies.

In this recent 2023 paper titled “Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies,” working group members explain why the development of new test articles for certain therapeutic modalities warrants nonclinical evaluation of ganglion structure and function.

How pathologists can help determine and interpret the effects of test articles on sensory ganglia

Sarah Cramer, DVM, PhD, DACVP and other members of the SRPC working group provide a framework for study pathologists to follow to determine whether ganglion changes are the result of exposure to test articles. This framework consists of several points to consider that span the duration of a study.

Guidance for the non-clinical evaluation of sensory ganglia is provided for the collection, processing, and evaluation of ganglia, covering the:

• Assignment of severity grades for microscopic findings
• Historical control data
• Determination of adversity

Points to consider are also provided based on the type of non-clinical toxicity study, including:

• GLP-compliant and non-GLP studies
• Research, efficacy, exploratory, and investigational studies

Reporting considerations are also explained, along with an in-depth look at correlations that exist in nonclinical toxicity studies between the functional and structural findings in sensory ganglia.

Access the paper from Toxicologic Pathology to learn more

Review and download the article here and learn how to better determine test article outcomes on sensory ganglia, so you can make better informed product development and regulatory decisions.