targeted-toxins

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)

García-Domínguez M (2025) NGF in neuropathic pain: Understanding its role and therapeutic opportunities. Curr Issues Mol Biol 47(2):93. doi: 10.3390/cimb47020093 PMID: 39996814

Objective: To determine the use of NGF as an important biomarker and therapeutic target in the management of neuropathic pain

Summary: Taking advantage of the multifaceted dynamics of NGF could provide effective pain management therapies to finally respond to the unmet needs of patients experiencing neuropathic pain. Kras et al. used saporin conjugates targeted to neurons involved in either peptidergic signaling and NGF-induced mechanical and thermal hypersensitivity in the forepaws.

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

See Also:

• Kras J et al. Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett 604:193-198, 2015.

Turner KL, Brockway DF, Hossain MdS, Griffith KR, Greenwalt DI, Zhang Q, gheres KW, Crowley NA, Drew PJ (2025) type-I nNOS neurons orchestrate cortical neural activity and vasomotion. bioRxiv 2025.01.21.634042. doi: 10.1101/2025.01.21.634042 PMID: 39896560

Objective: To uncover the role of a sparse but unusual population of genetically-distinct interneurons known as type-I nNOS neurons, using a novel pharmacological strategic to unilaterally ablate these neurons from the somatosensory cortex of mice.

Summary: Region-specific ablation produced changes in both neural activity and vascular dynamics, decreased power in the delta-band of the local field potential, reduced sustained vascular responses to prolonged sensory stimulation, and abolished the post-stimulus undershoot in cerebral blood volume. Coherence between the left and right somatosensory cortex gamma-band power envelope and blood volume at ultra-low frequencies was decreased, suggesting type-1 nNOS neurons integrate long-range coordination of brain signals. Authors also observed decreases in the amplitude of resting-state blood volume oscillations and decreased vasomotion following the ablation of type-I nNOS neurons.

Usage: Type-I nNOS neurons were selectively ablated with saporin conjugated to a substance P analog (SP-SAP, IT-07). Intracortical injection with 4 ng of either SAP conjugate or Blank-SAP (IT-21).

Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)

Zlatkovic J (2025) Gravitostat: A homeostatic regulator of body weight. Univ of Gothenburg Thesis.

Objective: To focus on elucidating central and peripheral physiological mechanisms behind load-induced body weight reduction.

Summary: The main findings in this thesis include the identification of a group of neurons activated by increased load in the medial Nucleus of Solitary Tract (mNTS) and the dorsal horn (DH) of the Lumbar Spine (LS) in mice.

Usage: Stereotaxic brain delivery of neurotoxin saporin conjugated with anti-dopamine-B-hydroxylase antibodies (5 ng, Anti-DBH-SAP, IT-03) was used as a method of targeted ablation of noradrenergic (NE) neurons in the Nucleus of the Solitary Tract in the brainstem.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Dogrul BN, Dogrul BN, Machado Kopruszinski C, Dolatyari Eslami M, Watanabe M, Luo S, Moreira de Souza LH, Vizin RL, Yue X, Palmiter RD, Navratilova E, Porreca F (2025) Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain. Pain 166(1):153-159. doi: 10.1097/j.pain.0000000000003360 PMID: 39058958

Objective: To determine whether rostral ventromedial medulla (RVM) mu opioid receptor (MOR)–expressing neurons are required for the expression and maintenance of established neuropathic pain.

Summary: Using chemogenetic silencing of MOR-expressing neurons, the study showed that inhibition of RVM-MOR cells reversibly reduces tactile allodynia and the affective component of neuropathic pain, demonstrating that descending facilitation from these neurons sustains chronic pain. The authors reference earlier findings using Dermorphin-SAP to confirm that complete ablation of MOR-expressing RVM neurons prevents neuropathic pain development without affecting acute surgical pain.

Usage: Dermorphin-SAP (IT-12) was referenced from prior studies as a method for selective ablation of MOR-expressing RVM neurons that prevented mechanical allodynia following spinal nerve ligation.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

See Also:

• Porreca F et al. Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the µ-opioid receptor. J Neurosci 21(14):5281-5288, 2001.

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 30(12):e70147. 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 15:1488951. 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)

Shivakumar AB, Mehak SF, Gupta A, Gangadharan G (2025) Medial septal cholinergic neurotransmission is essential for social memory in mice. Prog Neuropsychopharmacol Biol Psychiatry 136:111207. doi: 10.1016/j.pnpbp.2024.111207 PMID: 39615870

Objective: To identify the physiological link between medial septal dependent cholinergic theta oscillations in the hippocampus and social memory behavior.

Summary: Selective ablation of cholinergic neurons in the medial septum (MS) impaired social memory in mice, while their sociability and social novelty remained intact. Additionally, these mice showed an attenuation of cholinergic theta oscillations (3–7Hz) in the hippocampal dorsal CA2 (dCA2) region. Furthermore, enhancing dCA2 theta oscillations by elevating cholinergic signaling using acetylcholinesterase inhibitor rescued social memory deficit. Together, these results indicate that 1) medial septal cholinergic neurons are essential for modulating social memory and 2) cholinergic hippocampal theta oscillations contribute to social memory processes.

Usage: Ablation of cholinergic neurons in the MS using mu-p75-SAP (IT-16, 0.2μg/0.5μl).

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

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 (2025) 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 30(6):2381-2394. 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)