targeted-toxins

Kumbhare D, Rajagopal M, Toms J, Freelin A, Weistroffer G, McComb N, Karnam S, Azghadi A, Murnane KS, Baron MS, Holloway KL (2024) Deep brain stimulation of nucleus basalis of meynert improves learning in rat model of dementia. bioRxiv 2024.04.05.588271. doi: 10.1101/2024.04.05.588271 PMID: 38645266

Objective: To assess the effects of varying stimulation patterns and duration on learning in a dementia rat model.

Summary: Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) has been considered a potential treatment for dementia, but more study is needed to determine the ideal parameters for NBM stimulation. 192-IgG-SAP (Cat. IT-01) was used to lesion cholinergic neurons of rats creating a rat model of dementia upon which NBM deep brain stimulation could be tested. The desired destruction of neurons was 70-80% cholinergic population lesioned, which through a panel of concentrations was determined to be a 0.50 μg dose. The rat models of dementia were then tested for ideal type and duration of deep brain stimulation to improve operant learning test performance.

Usage: 192-IgG-SAP was bilaterally injected in the NBM in the following amounts: 0.00 (control), 0.15, 0.30, 0.50, and 0.75 μg in 0.5 μl PBS.

Related Products: 192-IgG-SAP (Cat. #IT-01)

MacLean MR, Walker OL, Arun RP, Fernando W, Marcato P (2024) Informed by cancer stem cells of solid tumors: Advances in treatments targeting tumor-promoting factors and pathways. Int J Mol Sci 25(7):4102. doi: 10.3390/ijms25074102 PMID: 38612911

Objective: To provide a comprehensive overview of the therapeutic targets associated with cancer stem cells (CSCs) of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/β-catenin, Notch, and Sonic Hedgehog.

Summary: Notably, many of the molecular targets and pathways associated with CSCs are also expressed in normal physiological processes and other stem cell populations. This presents a significant hurdle, as on-target effects of therapeutic interventions could inadvertently impact normal tissue function, leading to potential toxicity and adverse effects.

Usage: Bostad et al. used photochemical internalization to deliver Anti-CD133-SAP (IT-82) to WiDr colon cancer tumor-bearing mice, resulting in a significant decrease in tumor growth compared to control.

Related Products: Anti-CD133-SAP (Cat. #IT-82)

See Also:

• Bostad M et al. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48, 2015.

Choi PP, Wang Q, Brenner LA, Li AJ, Ritter RC, Appleyard SM (2024) Lesion of NPY receptor-expressing neurons in perifornical lateral hypothalamus attenuates glucoprivic feeding. Endocrinology 165(5):bqae021. doi: 10.1210/endocr/bqae021 PMID: 38368624

Objective: To explore the role of NPY receptor-expressing neurons in regulating feeding behavior in rats.

Summary: In response to glucose deficits, rats exhibit counter-regulatory mechanisms to stimulate feeding. To clarify the role of NPY-sensitive neurons, these neurons were selectively ablated using NPY-SAP. The results showed that while Saporin-lesioned rats exhibited reduced 2DG-induced feeding, there was no impact on 2DG-induced locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release.

Usage: NPY-SAP [IT-28] or Blank-SAP [IT-21] (50 ng per 100nL/site) was used to specifically lesion NPY receptor-expressing neurons in the perifornical lateral hypothalamus of male rats.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Nattkemper LA, Kim BS, Yap QV, Hoon MA, Mishra SK, Yosipovitch G (2024) Increased systemic levels of centrally acting b-type natriuretic peptide are associated with chronic itch of different types. J Invest Dermatol S0022-202X(24)00197-0. doi: 10.1016/j.jid.2024.02.026 PMID: 38522572

Objective: Examines plasma BNP levels and N-terminal pro-BNP levels in patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity.

Summary: Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale, particularly for patients with chronic pruritus of unknown origin. Based on this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, BNP-SAP lesions to mice determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord.

Usage: BNP-SAP was injected intrathecally (5 µg in 10 µL). One week later an itch agonist agent, ivBNP, was injected and itching was measured over an hour.

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

Huang L, Zhu W, Li N, Zhang B, Dai W, Li S, Xu H (2024) Functions and mechanisms of adenosine and its receptors in sleep regulation. Sleep Med 115:210-217. doi: 10.1016/j.sleep.2024.02.012 PMID: 38373361

Objective: To summarize the current research on the functions and possible mechanisms of adenosine and its receptors in regulating sleep and homeostatic control of sleep.

Summary: Authors concluded that the adenosine A1 receptor regulates sleep homeostasis by micro dialysis perfusion of antisense oligonucleotides against the RNA of the A1 Receptor in the magnocellular cholinergic region of the basal forebrain of a freely behaving rat. Adenosine has certain physiological significance in circadian rhythm, energy homeostasis, and sleep.

Usage: Loss of cholinergic cells was associated with a significant increase in sleep deprivation-induced adenosine level in the BF and a perfectly homeostatic sleep response.

Related Products: 192-IgG-SAP (Cat. #IT-01)

See Also:

• Kalinchuk AV et al. The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions. Neuroscience 157:238-253, 2008.

Décarie-Spain L, Hayes AMR, Lauer LT, Kanoski SE (2024) The gut-brain axis and cognitive control: A role for the vagus nerve. Semin Cell Dev Biol 156:201-209. doi: 10.1016/j.semcdb.2023.02.004 PMID: 36803834

Objective: To review evidence from rodent and human studies on how gastrointestinal vagus nerve signaling influences higher-order neurocognitive processes such as anxiety, motivation, learning, and memory.

Summary: The review highlights the integral role of gut-originating vagal pathways in regulating neurocognitive and affective functions, emphasizing their impact on adaptive behavioral responses and potential implications for neuropsychiatric disorders.

Usage: CCK-SAP (IT-31) was referenced in relation to prior studies involving gut vagal sensory ablation

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

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

Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement. bioRxiv 2024.03.07.583670. doi: 10.1101/2024.03.07.583670

Objective: Investigate the neuroprotective effect of treatment with the CB1 cannabinoid agonist, WIN55,212-2, against cholinergic degeneration.

Summary: The endocannabinoid (eCB) system plays a role in modulating learning and memory processes controlled by cholinergic neurotransmission. The authors propose that activation of this system is neuroprotective against cholinergic degeneration, such as what occurs in Alzheimer’s disease (AD). In a 192-IgG-SAP (Cat. IT-01) induced model of AD, a restoration of memory and learning was observed when rats were administered the CB1 cannabinoid agonist, WIN55,212-2.

Usage: Rats received injections of 192-IgG-saporin (130 ng/µl) into the nucleus basalis magnocellularis.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Luna-Munguia H, Gasca-Martinez D, Garay-Cortes A, Coutiño D, Regalado M, de Los Rios E, Villaseñor P, Hidalgo-Flores F, Flores-Guapo K, Benito BY, Concha L (2024) Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus. Mol Neurobiol 61(10):1-21. doi: 10.1007/s12035-024-04069-9 PMID: 38443731

Objective: To evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.

Summary: Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Regarding the pilocarpine-induced status epilepticus, an increased mortality rate was observed. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Usage: Injection of 192-IgG-SAP (375 ng/μl dissolved in sterile 0.1X PBS) and GAT1-SAP (325 ng/μl dissolved in sterile 0.1X PBS) into the MS to selectively target choline neuron or GABA populations of the medial septum, respectively.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)

Kitawi R, Ledger S, Kelleher AD, Ahlenstiel CL (2024) Advances in HIV gene therapy. Int J Mol Sci 25(5):2771. doi: doi.org/10.3390/ijms25052771

Objective: This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.

Summary: The long-term or permanent expression of anti-HIV genes and the modification of CD4+ and CD34+ cells to render them resistant to infection or to allow the disruption of the HIV life cycle are important strategies in the quest to achieve a HIV cure.

Usage: Authors referenced CD117 antibody conjugated to saporin via streptavidin (IT-27, IT-83), which enabled >99% depletion of endogenous HSCs in NSG mice and non-human primates.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.

Díaz-Jara E, Pereyra K, Vicencio S, Olesen MA, Schwarz KG, Toledo C, Díaz HS, Quintanilla RA, Del Rio R (2024) Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation. Redix Biol 69:102992. doi: 10.1016/j.redox.2023.102992 PMID: 38142585

Objective: To determine the impact of partial deletion of SOD2 expression on (1) O2.−accumulation in the Retrotrapezoid nucleus (RTN), (2) central ventilatory chemoreflex function, and (3) disordered-breathing as well as cellular localization of SOD2 in the RTN of healthy mice.

Summary: Results showed that SOD2+/− mice displayed reductions in SOD2 levels and high O2-formation and mitochondrial dysfunction within the RTN compared to wild type. Additionally, SOD2+/−mice displayed a heightened ventilatory response to hypercapnia and exhibited overt signs of altered breathing patterns.

Usage: Recent research has shown that removing some RTN chemoreceptor neurons using substance P-conjugated saporin toxin can normalize central chemoreflex and respiratory disorders in animals with heart disease, highlighting the significance of RTN neurons in the pathological process of central chemoreflex potentiation.

Related Products: SP-SAP (Cat. #IT-07)