The blood-brain barrier (BBB) restricts many therapeutic agents, including gene therapy vectors, from reaching the central nervous system (CNS) when delivered through systemic routes.

In nonclinical studies, accurate positioning and continuous monitoring of gene therapy interventions are vital for ensuring safety and efficacy. Attentive Science has expanded its contract research capabilities to include intrathecal dosing competences, which delivers drugs directly into the cerebrospinal fluid (CSF) around the spinal cord. This targeted dosing approach is beneficial for treating CNS diseases including neurodegenerative or neuromuscular disorders where the gene therapy needs to reach the target cells to be effective.

Test articles delivered into the CNS can result in side effects which can range widely in severity and type, depending on the specific drug, its dosage, and individual test subject factors:

Potential side effects include:

Heightened sensitivity: With direct access to the CNS, there is the potential of high concentrations of the therapeutic agent being available within the CNS. Increased availability means both increased intended therapeutic effects and unintended side effects.

Drug Distribution: The distribution of drugs in the CSF can vary depending on the properties (molecular weight, charge, and lipid solubility of the drug) which may result in an uneven distribution, causing certain areas within the CNS to receive higher doses, leading to focal side effects.

Localized Toxicity: Neurotoxic drugs or those with a narrow therapeutic index may be of greater concern because a high concentration of the therapeutic agent within the CNS can sometimes lead to localized toxicity, affecting surrounding neurons and supporting cells.

Drug Metabolism and Clearance: The CSF lacks the metabolic and clearance mechanisms present in the bloodstream, which can lead to prolonged exposure to the test article within the CNS, increasing the risk of side effects, especially if the test article has CNS-depressant effects.

Immunologic Reactions: If the test article is not well-tolerated by CNS tissues, there may be a tendency for an immune response. This can result in localized inflammation and neurotoxicity, manifesting as CNS side effects like headache, nausea, and more severe neurological symptoms.

CNS side effects from intrathecal dosing are a crucial consideration, especially for nonclinical studies or therapeutic settings where the risk of neurotoxicity needs careful monitoring.

Attentive Science enhances its research service offering by introducing intrathecal dosing capabilities

Intrathecal dosing offers significant advantages for targeting the CNS, and while there are considerations to address, they can be managed effectively with proper planning and expertise. For example:

a) Though it is an invasive procedure, it can be safely performed with adequate technical skill and careful attention.

b) Distribution of the therapy may vary, but advancements delivery techniques continue to enhance its effectiveness.

c) While dose adjustments after administration are not possible, careful pre-administration planning and precise dosing ensure the therapy is optimized for the target response.

By focusing on these addressable considerations, intrathecal dosing remains a valuable and impactful approach for CNS therapies as well as many other diverse medical needs. Attentive Science’s mission is be at the fore-front of scientific advancement, and by combing with capabilities such as C-Arm Fluoroscopy imaging, risks associated with this specialized route of administration are mitigated.

Contact us to learn how Attentive Science can help you achieve your goals efficiently and accurately.