Intradermal and Subcutaneous Botulinum Toxin Type A Injections Do Not Differ in the Induction of Neutralizing...

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Botulinum toxin type A (BoNT/A) is used for muscle hyperactivity via intramuscular injection.
• New applications like neuropathic pain require subcutaneous (SC) or intradermal (ID) administration.
• The potential for anti-drug antibodies (ADAs) with SC/ID BoNT/A is unknown.

Purpose of the Study:

• To investigate if repeated SC or ID injections of BoNT/A elicit ADAs.
• To determine if ADA formation is dose-dependent and route-dependent.

Main Methods:

• Mice received 5 ID or SC injections of 150 kDa BoNT/A, inactive mutant BoNT/A (DRBoNT/A), or inactivated toxoid (IA-BoNT/A).
• Total ADAs were measured by immunoassay.
• Neutralizing ADAs were assessed using an in vivo digit abduction score (DAS) assay.

Main Results:

• DRBoNT/A and IA-BoNT/A induced ADAs, while therapeutic doses of 150 kDa BoNT/A did not.
• Therapeutic doses of 150 kDa BoNT/A resulted in unrestricted DAS, indicating no neutralizing ADAs.
• High doses of DRBoNT/A or IA-BoNT/A showed minimal DAS, indicating high neutralizing ADA titers.
• No significant differences in ADA formation were observed between ID and SC routes.

Conclusions:

• Repeated therapeutic SC or ID BoNT/A injections do not induce ADA formation in mice.
• The antibody response to BoNT/A is primarily dependent on protein load, not the administration route.
• While higher ADA concentrations can occur with ID injections at intermediate doses, neutralizing ADA levels remain similar across routes.