Targeting Topics 01q1

Loss of nerve: a molecular approach to better treatment of chronic pain.

Friedrich MJ.

JAMA 283(2):187-188, 2000. PMID: 10634324

The use of SP-SAP (Cat. #IT-07) as a promising new method for chronic pain relief is discussed in this review article. Chronic pain has classically been treated in ways that frequently have adverse effects on the patient’s quality of life. Friedrich touches on recently developed toxins that are useful in techniques of molecular neurosurgery. These techniques allow the dissection of pain pathways in the brain and spinal cord which will provide not only a greater understanding of these pathways but also potential therapies for chronic pain and other pain conditions.

Mab-ZAP: a tool for evaluating antibody efficacy for use in an immunotoxin.

Kohls MD, Lappi DA.

Biotechniques 28(1):162-165, 2000. PMID: 10649788

Immunotoxins are useful tools for elimination of specific cell populations in vitro and in vivo for research and therapeutic applications. One of the factors limiting the use of immunotoxins is the selection of an appropriate antibody. Advanced Targeting Systems has created a reagent that allows researchers to select antibodies with the desired characteristics before an immuntoxin is made, purified, and assayed. Using a goat anti-murine IgG coupled to the ribosome-inactivating protein saporin (Mab-ZAP, Cat. #IT-04), researchers can screen hundreds of antibodies in a time and cost-effective manner.

Selective impairment of corticotropin-releasing factor1 (CRF1) receptor-mediated function using CRF coupled to saporin.

Maciejewski-Lenoir D, Heinrichs SC, Liu XJ, Ling N, Tucker A, Xie Q, Lappi DA, Grigoriadis DE.

Endocrinology 141(2):498-504, 2000. PMID: 10650928

Corticotropin-releasing factor 1 (CRF1) is a 41-amino acid peptide which mediates many of the body’s behavioral, autonomic, immune, and endocrine responses to stress. Reduced activation of the CRF systems plays a role in a variety of psychiatric and metabolic disease states. Maciejewski-Lenoir et al. have developed a CRF-SAP targeted toxin that can eliminate ce (Cat. #IT-13) lls expressing the CRF1 but not CRF2α receptors. These data indicate that CRF-SAP may be useful as a tool to examine receptor- selective impairment of CRF system function.

Antibody for human p75 LNTR identifies cholinergic basal forebrain of non-primate species.

Tremere LA, Pinaud R, Grosche J, Hartig W, Rasmusson DD.

Neuroreport 11(10):2177-2183, 2000. PMID: 10923666

192-SAP (Cat. #IT-01) is a highly successful reagent for eliminating cholinergic neurons in rats. Because the targeting antibody only recognizes rat p75, it is unable to be used in other species. Tremere et al. have stained basal forebrain sections with ME20.4, a monoclonal antibody to human p75 (Cat. #AB-N07) and found excellent cross- reactivity in dog, raccoon, cat, pig and rabbit. The authors state that an ME20.4- saporin conjugate could be used to produce cholinergic basal forebrain lesions in several species. Last quarter, ATS highlighted the use of ME20.4-SAP in the rabbit (Targeting Trends 1:1, 2000).

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization.

Lehmann O, Jeltsch H, Lehnardt O, Pain L, Lazarus C, Cassel JC.

Eur J Neurosci 12(1):67-79, 2000. PMID: 10651861

Lesioning of septohippocampal pathways has often been used as a model for Alzheimer’s disease because these lesions alter cognitive capabilities such as spatial memory. Recent work in the behavioral neurosciences has shown that other neurotransmitter systems such as GABAergic, noradrenergic, and serotonergic systems also play a role in learning and memory. Lehmann et al. combined the effects of the cholinergic immunotoxin 192-SAP (Cat. #IT-01) and the serotonergic toxin 5,7-dihydroxytryptamine to examine interactions between these two pathways. The effects of lesioning these two pathways in concert indicate that they both play roles in cognitive functions related to working memory.

Effects of cholinergic depletion on neural activity in different laminae of the rat barrel cortex.

Herron P, Schweitzer JB.

Brain Res 872(1-2):71-76, 2000. PMID: 10924677

192-SAP (Cat. #IT-01) 8.0 μg/300 g body weight, nucleus basalis of Meynert

Sustained effect of metrifonate on cerebral glucose metabolism after immunolesion of basal forebrain cholinergic neurons in rats.

Bassant MH, Poindessous-Jazat F, Schmidt BH.

Eur J Pharmacol 387(2):151-162, 2000. PMID: 10650155

192-SAP (Cat. #IT-01) 134 ng in 0.2 μl, basal forebrain

Development of a method for intraparenchymal infusions of 192 IgG-saporin: a comment on Pizzo et al. (1999).

Sarter M, Bruno JP, Miner LA, McGaughy J.

J Neurosci Methods 96(2):169-170, 2000. PMID: 10720682

Letter pertaining to use of 192-SAP (Cat. #IT-01)

Nerve growth factor (NGF) augments cortical and hippocampal cholinergic functioning after p75NGF receptor-mediated deafferentation but impairs inhibitory avoidance and induces fear-related behaviors.

Winkler J, Ramirez GA, Thal LJ, Waite JJ.

J Neurosci 20(2):834-844, 2000. PMID: 10632613

192-SAP (Cat. #IT-01) 1.0 or 2.7 μg in 10 μl, intracerebroventricular

Preserved olfactory short-term memory after combined cholinergic and serotonergic lesions using 192 IgG-saporin and 5,7-dihydroxytryptamine in rats.

Wirth S, Lehmann O, Bertrand F, Lazarus C, Jeltsch H, Cassel JC.

Neuroreport 11(2):347-350, 2000. PMID: 10674484

192-SAP (Cat. #IT-01) 2 μg, intracerebroventricular

Pain control: breaking the circuit.

Hunt SP.

Trends Pharmacol Sci 21(8):284-287, 2000. PMID: 10918627

Review and analysis of the value of SP-SAP (Cat. #IT-07) in research and as a therapeutic.

In vivo [125I]-iodobenzovesamicol binding reflects cortical cholinergic deficiency induced by specific immunolesion of rat basal forebrain cholinergic system.

Sorger D, Schliebs R, Kampfer I, Rossner S, Heinicke J, Dannenberg C, Georgi P.

Nucl Med Biol 27(1):23-31, 2000. PMID: 10755642

192-SAP (Cat. #IT-01), 2 μg into each lateral ventricle

The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins.

McGaughy J, Everitt BJ, Robbins TW, Sarter M.

Behav Brain Res 115(2):251-263, 2000. PMID: 11000424

Review and comparison of immunolesioning techniques using 192-SAP (Cat. #IT-01) and ME20.4-SAP (Cat. #IT-15)

Brainstem noradrenergic control of nociception is abnormal in the spontaneously hypertensive rat.

Taylor BK, Roderick RE, Basbaum AI.

Neurosci Lett 291(3):139-142, 2000. PMID: 10984626

anti-DBH-SAP (Cat. #IT-03), 5 μg

Increased susceptibility to generalized seizures after immunolesions of the basal forebrain cholinergic neurons in rats.

Silveira DC, Holmes GL, Schachter SC, Geula C, Schomer DL.

Brain Res 878(1-2):223-227, 2000. PMID: 10996157

192-SAP (Cat. #IT-01), 4 μg intracerebroventricular injection