Cover Article: Celebrating Twenty Years of Science Advanced Targeting Systems (founded 22 Apr 1994)

Advanced Targeting Systems’ first product, 192-IgG-SAP, answered a long-sought request from behavioral neuroscientists: a neurotoxin for the cholinergic neurons of the basal forebrain. Over the years it has become the classic in the field and has changed the way that we think about those neurons and their role in learning and memory.


Substance P-saporin (SP-SAP) rapidly became an item of interest due to the impact on chronic pain models. As one renowned Neuroscientist stated: “No one expected these results,” and they have been replicated many times over. Aside from that, SP-SAP opened new ways to analyze that jungle of fibers in the spinal cord and presaged a series of products that are dissecting and establishing function of neurons in the spinal cord.

Yellow staining for saporin after internalization of SP-SAP by this single spinal cord neuron.
Photo Credit: S. Rogers, J. Ghilardi, P. Mantyh

Bombesin-SAP is gastrin-releasing peptide (made from the frog skin version discovered by Esparmer and co-workers), attached to saporin. This targetd toxin made a splash by demonstrating that the urge to itch could be stopped by removing GRP receptor-positive neurons in the spinal cord. This led to renewed interests and approaches in the itch field and the relationship between pain and itch. A new series of toxins sprang forth to foster the discussion.

Selective ablation of GRPR+ neurons in the spinal cord. (A-B)
GRPR expression detected by in situ hybridization. (C-D)
NK1 receptor expression detected by immunocytochemistry
in the dorsal horn. Scale bar: 100 μm
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