Northwestern Events Calendar


Department of Pharmacology Guest Speaker - Philip Band, PhD

When: Monday, November 20, 2023
3:00 PM - 4:00 PM CT

Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Melissa Daley  

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings, Academic


Department of Pharmacology, Speaker: Philip Band, PhD

Research Professor, Departments of Orthopedic Surgery, Biochemistry and Molecular Pharmacology

New York University Grossman School of Medicine

"Specific Delivery of Therapeutic Antibodies to the Neuronal Cytoplasm Using Recombinant Derivatives of Botulinum Neurotoxin"

Botulinum neurotoxin (BoT) is categorized by CDC as a Tier 1 biodefense threat, the same
category as hemorrhagic viridae like Ebola. BoT is also a $5B pharmaceuKcal product with
mulKple therapeuKc indicaKons. Background will be provided on the mechanism of BoT toxicity and its clinical development as a pharmaceuKcal neuromodulator, focusing on its unique ability to specifically target the neuronal cytoplasm at picomolar doses. A plaOorm for producing recombinant BoT (rBoT) derivaKves will be described, including the use of atoxic rBoT derivaKves to specifically deliver single chain anKbodies to the cytoplasm of neurons in the form of rBoT anKbody fusion proteins (rBoT-AFPs). Proof of concept for rBoT-AFPs has been established in three species, using an atoxic derivaKve of BoT/C1 (C1ad) geneKcally fused to a VHH anKbody (B8) that inacKvates the toxic BoT/A1 protease. The B8-Cad fusion protein delivers the B8 anKbody to the neuronal cytoplasm of BoT/A1-intoxicated animals, where it inacKvates the BoT/A1 protease causing botulism symptoms. B8-Cad rescues BoT/A1-intoxicated animals at Kmes post-intoxicaKon when convenKonal anKbodies are ineffecKve, because they cannot target the BoT/A1 protease that resides in the neuronal cytoplasm, requiring mechanical venKlaKon for weeks to months to preserve life. Ongoing work is opKmizing the inherent capabiliKes of rBoTs to undergo retrograde and transsynapKc transport, creaKng a pathway for their delivery to the CNS to treat chronic pain and neurodegeneraKve disease.

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