targeted-toxins

Hung LY, Alves ND, Del Colle A, Talati A, Najjar SA, Bouchard V, Gillet V, Tong Y, Huang Z, Browning KN, Hua J, Liu Y, Woodruff JO, Juarez D, Medina M, Posner J, Tonello R, Yalcinkaya N, Israelyan N, Ringel R, Yang L, Leong KW, Yang M, Sze JY, Savidge T, Gingrich J, Shulman RJ, Gershon MD, Ouellet A, Takser L, Ansorge MS, Margolis KG (2025) Intestinal epithelial serotonin as a novel target for treating disorders of gut-brain interaction and mood. Gastroenterology 168(4):754-768. doi: 10.1053/j.gastro.2024.11.012 PMID: 39672518

Objective: To investigate how intestinal epithelial serotonin influences mood and gastrointestinal function, and to identify gut-targeted therapies for mood disorders and disorders of gut-brain interaction (DGBI).

Summary: Selective deletion of the serotonin transporter (SERT) from the intestinal epithelium reduced anxiety- and depression-like behaviors in mice without affecting gut motility or cognition. These effects were dependent on afferent vagal signaling. Conversely, depleting intestinal serotonin increased anxiety. A human birth cohort study linked in utero SSRI/SNRI exposure to a higher risk of functional constipation, supporting a gut-brain role in DGBI.

Usage: CCK-SAP (IT-31) was bilaterally injected into the nodose ganglia, and after one week, tests of anxiety and depression were performed.

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

Saavedra FM, Brotto DB, Joag V, Matson CA, Nesmiyanov PP, Herzberg MC, Vezys V, Masopust D, Stolley JM (2025) Triggering mouth-resident antiviral CD8+ T cells potentiates experimental periodontitis. Mucosal Immunol S1933-0219(25)00021-2. doi: 10.1016/j.mucimm.2025.02.003 PMID: 39988203

Objective: To determine if local reactivation of antigen-specific oral CD8+ TRM exacerbates ligature-induced periodontitis (LIP) in mice.

Summary: Topical application of virus-mimicking peptides during LIP increased alveolar bone loss, enhanced gingival and cervical lymph node inflammation, and upregulated gingival genes linked to innate immunity and cytotoxicity. Depleting CD103+ CD8+ TRM with αCD103-SAP prior to LIP prevented disease exacerbation, implicating these cells in periodontitis pathology.

Usage: Anti-CD103-SAP (IT-50) was administered in PBS at 5 μg (day -4), 2 μg (day 0), and 2 μg (day +4) relative to LIP induction.

Related Products: Anti-CD103-SAP (Cat. #IT-50)

Dib C, Queenan J, Willner H, Swartzrock L, Charlesworth C, Denis M, Davis J, Nakauchi H, Liu DR (2025) Combining hsc base-editing with anti-cd117 antibody conditioning to correct severe combined immunodeficiency disorder in a novel mouse model. Transplantation and Cellular Therapy 31(2):S253-S354. doi: 10.1016/j.jtct.2025.01.385

Objective: To test whether base-edited hematopoietic stem cells (HSPCs) combined with non-genotoxic antibody conditioning can correct severe combined immunodeficiency (SCID) in a novel Rag2 mutant mouse model.

Summary: Base-editing delivered via engineered virus-like particles successfully corrected Rag2 mutations in HSPCs, which restored lymphocyte development following transplantation. Conditioning with an Anti-CD117-Saporin conjugate enabled efficient engraftment without irradiation toxicity, demonstrating a safer strategy for SCID treatment.

Usage: Mice were conditioned with Anti-CD117-SAP (IT-83) at 1.5 mg/kg intravenously prior to transplantation of base-edited or wild-type HSPCs.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

Prince C, Kumar D, Chambliss C, Okalava J, Malik S, Doering CB, Spencer HT, Archer D. Chandrakasan S (2025) Clinically relevant non-genotoxic conditioning with cd117 immunotoxin promotes robust donor chimerism and amelioration of sickle cell disease in a murine model. Transplantation and Cellular Therapy 31(2):S178. doi: 10.1016/j.jtct.2025.01.274

Objective: To investigate the efficacy of an Anti-CD117-Saporin conjugate as part of a non-genotoxic HCT strategy in a sickle cell disease (SCD) mouse model.

Summary: An Anti-CD117-SAP, combined with clinically relevant immunosuppression, achieved stable donor chimerism and corrected hematologic abnormalities in SCD mice. This conditioning regimen avoided transfusion requirements, graft-versus-host disease, and transplant-related mortality typical of TBI or busulfan-based approaches.

Usage: HbSS-Townes mice were conditioned with ATG and B cell depletion followed by Anti-CD117-SAP (IT-83, 0.75 µg/g) prior to HCT with HbAA-Townes donor marrow.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

Vringer M, Zhou J, Gool JK, Bijlenga D, Lammers GJ, Fronczek R, Schinkelshoek MS (2024) Recent insights into the pathophysiology of narcolepsy type 1. Sleep Med Rev 78:101993. doi: 10.1016/j.smrv.2024.101993 PMID: 39241492

Objective: To focus on recent insights into Narcolepsy type 1 (NT1) pathophysiology, discussing structural and functional changes, immune system involvement, genetic findings, and future perspectives for the pathophysiology and treatment options.

Summary: Narcolepsy type 1 (NT1) is one of the central disorders of the hypersomnolence and results from hypocretin (Hcrt, also nown as orexin) deficiency in the brain. The development of HcrtR2-specific or dual HcrtR1 and HcrtR2 agonists, has shown promising results in pre-clinical and clinical trials. These agonists can potentially become the first drugs to directly target the Hcrt system and replace the shortage of Hcrt in NT1.

Usage: Hcrt-2 conjugated to the ribosome-inactivating toxic protein saporin (Orexin-SAP, Cat #IT-20) eliminated up to 90% of Hcrt neurons but also caused significant loss of neighboring neuronal cells, such as Melanin-concentrating hormone (MCH) neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Wang D, Wei SN, Zhang L, Lang ZC, Wang SN, Cheng B, Lu Y, Wang X, Wang W, Li FS, Zhang H (2024) Impaired basal forebrain cholinergic neuron gdnf signaling contributes to perioperative sleep deprivation–induced chronicity of postsurgical pain in mice through regulating cholinergic neuronal activity, apoptosis, and autophagy. CNS Nerusci Ther doi: 10.1111/cns.70147 PMID: 39639706

Objective: This study investigated the roles of lateral basal forebrain glial cell line–derived neurotrophic factor (GDNF). The authors researched GDNF and the associated signaling and cholinergic neuron activity, apoptosis, and autophagy dysfunction in sleep deprivation–induced increased risk of chronic postsurgical pain (CPSP) in mice.

Summary: Perioperative sleep deprivation promotes chronicity of postsurgical pain possibly through decreasing basal forebrain GDNF signaling and causing cholinergic neuronal apoptosis and autophagy dysfunction.

Usage: To ablate the basal forebrain cholinergic neurons, 0.4μg/μL of mu p75-SAP (IT-16) in 0.6μL phosphate-buffered saline was used 3 weeks before the Skin/Muscle Incision and Retraction modeling.

Related Products: mu p75-SAP (Cat. #IT-16)

Lewis RD, Keilholz AN, Smith CL, Burd EA, Nichols NL (2024) Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats. Front Physiol 15 doi: 10.3389/fphys.2024.1488951 PMID: 39703667

Objective: To study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited.

Summary: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats, and that astrocytes were increased and exhibited reactive morphology in the phrenic motor nucleus of CTB-SAP rats. This work suggests that TNFR1 could be used as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease.

Usage: Intrapleural injection of CTB-SAP (25μg dissolved in PBS) to target respiratory motor neurons.

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

Morishata Y, Fuentes I, Gonzalez-Salinas S, Favate J, Mejaes J, Zushida K, Nishi A, Hevi C, Goldsmith N, Buyske S, Sillivan SE, Miller CA, Kandel ER, Uchida S, Shah P, Alarcon JM, Barker DJ, Shumyatsky GP (2024) Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction. Molexular Psychiatry doi: 10.1038/s41380-024-02843-8 PMID: 39580604

Objective: To investigate neural circuits serving the dopamine function for fear extinction and PTSD.

Summary: Results demonstrate that gastrin-releasing peptide regulates dopamine function in stress-enhanced fear processing and identifies Grp as the first gene known to regulate dopaminergic control of fear extinction.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) (80 ng/µl) dissolved in saline were injected bilaterally into the basolateral amygdala (AP: -2.0 mm, ML: ±3.25 mm, DV: -4.3 mm) in 0.3 µl volume.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Ammar AO (2024) Involvement of peptidergic Edinger-Westphal nucleus in the neurobiology of migraine and acute alcohol exposure. Univ Pecs Thesis.

Objective: To confirm the role of Edinger-Westphal nucleus/urocortin1 (EWcp/UCN1) neurons in migraine. They hypothesized that selective ablation of EWcp/UCN1 neurons will influence the migraine-related behaviors induced by CGRP.

Summary: Upon selective ablation of EWcp/UCN1 neurons, authors examined the migraine-related behaviors in response to calcitonin gene-related peptide (CGRP) treatment. Leptin-SAP treatment significantly reduced the number of UCN1 immunoreactive neurons in the EWcp compared to naïve mice. Before ablation of EWcp/UCN1 neurons, CGRP treatment significantly reduced the periorbital withdrawal threshold compared to saline.

Usage: For selective UCN1 neuron ablation, 50 nl of Leptin-SAP was microinjected into the rostral and caudal parts of the EWcp area.

Related Products: Leptin-SAP (Cat. #IT-47)

Schaible HG, König C, Ebersberger A (2024) Spinal pain processing in arthritis: Neuron and glia (inter)actions. J Neurochem 168(11):3644-3662. doi: 10.1111/jnc.15742 PMID: 36520021

Objective: To address the mechanisms of spinal sensitization evoked by arthritis.

Summary: Neutralization of spinal cytokines by intrathecal interventions attenuates mechanical hyperalgesia. This effect may in part result from local suppression of spinal sensitization and in part from efferent effects which attenuate the inflammatory process in the joint. In summary, arthritis evokes significant spinal hyperexcitability which is likely to contribute to the phenotype of arthritis pain in patients

Usage: Selective microglia destruction with the immunotoxin saporin conjugated to Mac1 antibody (Mac-1-SAP Cat #IT-06, recognizes Mac1 receptor on microglia) attenuated the development of hyperalgesia.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)