2021 Targeting Trends Review

Castiello MC, Bosticardo M, Sacchetti N, Calzoni E, Fontana E, Yamazaki Y, Draghici E, Corsino C, Bortolomai I, Sereni L, Yu HH, Uva P, Palchaudhuri R, Scadden DT, Villa A, Notarangelo LD (2021) Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6. doi: 10.1016/j.jaci.2020.04.033

Objective: To improve multi-lineage engraftment using non-genotoxic conditioning with Anti-CD45-Saporin.

Summary: Conditioning with Anti-CD45 antibody-drug conjugates may represent a novel and safe conditioning regimen for patients with RAG deficiency and other inborn errors of immunity.

Usage: Intravenous injection of Anti-CD45-SAP (3 mg/kg).

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Chew C, Sengelaub DR (2021) Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle. Dev Neurobiol 81(1):22-35. doi: 10.1002/dneu.22794

Objective: To determine where the necessary site of androgen action is for exercise-driven neuroprotective effects on induced dendritic atrophy.

Summary: Exercise following neural injury exerts a protective effect on motoneuron dendrites, which acts via androgen receptor action at the target muscle.

Usage: Motoneurons innervating the left vastus medialis (VM) muscle were selectively killed by intramuscular injection of cholera toxin-conjugated saporin (CTB-SAP).

Related Products: CTB-SAP (Cat. #IT-14)

Nelson TS, Taylor BK (2021) Targeting spinal neuropeptide Y1 receptor-expressing interneurons to alleviate chronic pain and itch. Prog Neurobiol 196:101894. doi: 10.1016/j.pneurobio.2020.101894

Summary: Intrathecal administration of NPY-SAP reduced several operant and cognitive measures of Complete Freund’s adjuvant (CFA)-induced allodynia, including responsiveness to cold temperatures, feeding interference, and an escape task, but did not interfere with systemic morphine-induced analgesia. (Wiley et al.) Similar to the spared nerve injury (SNI) model of neuropathic pain, NPY-SAP dose-dependently reduced the development of mechanical allodynia (hindpaw withdrawal response to von Frey filaments), mechanical hyperalgesia (response to blunt pin), and cold allodynia (hindpaw withdrawal response duration to acetone droplet evaporation). (Nelson et al.) Together, these directed lesion studies support the idea that the Y1-IN subpopulation of dorsal horn neurons is necessary for the maintenance of both mechanical and cold modalities of nociceptive transmission in chronic pain states.

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See Also:

• Wiley RG et al. Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147, 2009.
• Nelson TS et al. Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248, 2019.

Puente BR (2021) Chronic pain in dogs (Dolor crónico en el perro). Zaragoza Spain: Gruppo Asis Biomedia, S. L..

Summary: The author presents a thorough overview of aspects of canine chronic pain. He includes SP-SAP (Substance P-Saporin) as an experimental drug, “its use as an adjuvant analgesic in dogs with bone cancer has been studied,”

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See Also:

• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.

Ma X, Fu S, Yin Y, Wu Y, Wang T, Xu G, Liu M, Xu Y, Tian J, Jiang G (2021) Aberrant functional connectivity of basal forebrain subregions with cholinergic system in short-term and chronic insomnia disorder. J Affect Disord 278:481-487. doi: 10.1016/j.jad.2020.09.103

Summary: Previous animal studies have identified the cholinergic basal forebrain (CBF) as a crucial structure in sleep-wake cycle modulation and lesion or inactivation of the BF has been found to increase delta electroencephalogram activity, disturb behavioral arousal, and reduce sleep. They reference Kaur et al. using 192-IgG-SAP to lesion the CBF to examine the role of these neurons in sleep behavior.

See: Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.

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Lee TH, Yau SY (2021) From obesity to hippocampal neurodegeneration: Pathogenesis and non-pharmacological interventions. Int J Mol Sci 22(1):201. doi: 10.3390/ijms22010201

Summary: This review provides insights into how chronic metabolic disorders, like obesity, could impair brain health and cognitive functions in later life. The authors reference the use of CCK-SAP into the nodose ganglia to impair spatial memory and contextual episodic memory.

See: Suarez AN et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181, 2018.

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Pazo M, Salluce G, Lostalé-Seijo I, Juanes M, Gonzalez F, Garcia-Fandiño R, Montenegro J (2021) Short oligoalanine helical peptides for supramolecular nanopore assembly and protein cytosolic delivery. RSC Chem Biol 2:503-512. doi: 10.1039/D0CB00103A

Related Products: Saporin (Cat. #PR-01)

Cromwell HC (2021) Characterizing the neural substrate of reward with the use of specific brain lesions. Fakhoury M (Ed.): The Brain Reward System. Neuromethods. 165. Humana, New York, NY doi: 10.1007/978-1-0716-1146-3_3

Summary: This review is focused on experimental lesions and work using the rodent model examining the neural substrates of reward processing. Saporin is listed as a neurotoxin used to target selective neuronal populations with success.

See: Pappas BA et al. Neonatal 192 IgG-saporin lesion of forebrain cholinergic neurons: focus on the life span?. Neurosci Biobehav Rev 27(4):365-376, 2003.

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