Abstract Details

Title Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality versus Wishful Thinking?

Topic General Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 2-003

Background The blood-brain barrier is known to inhibit the central nervous system (CNS) penetration of 98% of small molecule drugs and virtually all biologic agents. VAPs such as regadenoson, adenosine, and labradimil have been shown in animal studies to transiently disrupt the BBB. Regadenoson is currently being studied in humans to determine if it can improve drug delivery to the CNS. However, there are many other VAPs which could also be candidate drugs for this purpose.

Objective To identify and rank vasoactive peptides (VAPs) that may transiently open the blood-brain barrier (BBB) based on the evidence in the literature.

Design/Methods We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the BBB and the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the BBB, we devised a four-tier classification system to organize data available in the literature.

Results We identified 35 VAPs with potential BBB permeability-altering properties. To date, none of these has been shown to open the BBB in humans. 12 VAPs increased BBB permeability in rodents. The remaining 23 had favorable physiologic effects on blood vessels but lack specific information on permeability changes to the BBB. We ranked VAPs in a four-tier system related to their known physiologic actions.

Conclusions Rodent studies show that analogs of bradykinin and adenosine transiently disrupt the BBB leading to higher chemotherapy concentrations. However, VAPs remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other CNS diseases. Dozens of VAPs have yet to be formally evaluated for this important clinical effect. This retrospective review summarizes the available data on VAPs, highlighting agents that deserve further in vitro and in vivo investigations.

Authors/Disclosures
Matthew Smith-Cohn, DO (Barrow Neurological Institute) PRESENTER	Dr. Smith-Cohn has nothing to disclose.
	No disclosure on file
Stuart A. Grossman, MD (The Brain Cancer Program At Johns Hopkins)	Stuart A. Grossman, MD has stock in Myosin Therapeutics Inc. The institution of Stuart A. Grossman, MD has received research support from National Cancer Institute. Stuart A. Grossman, MD has received personal compensation in the range of $5,000-$9,999 for serving as a Member, Brain Malignancy Steering Committee with National Cancer Institute.