Keilholz AN, Lopez S, Attari M, Nguyen NP, Henry J, Smith CL, Feldberg A, Osman KL, Golzy M, Bunyak F, Lever TE, Nichols NL (2026) Impact of tongue exercise on hypoglossal axis survival, structure, and output in a rodent model of hypoglossal motor neuron degeneration. J Neurophysiol doi: 10.1152/jn.00631.2024 PMID: 42012472
Objective: To investigate the effects of a high-repetition/low-resistance tongue exercise paradigm on XII axis survival, structure, and output in adult male Sprague Dawley rats.
Summary: Intralingual injections of CTB-SAP result in decreased XII motor neuron survival and degenerative changes in the XII nerve consistent with what is seen in many motor neuron diseases. While these deficits are not mitigated by tongue exercise, the authors observed increased microglial fractional area/density in the XII nucleus of CTB-SAP + exercise rats.
Usage: Rats received intralingual injection of either CTB-SAP (IT-14) or unconjugated CTB + SAP (PR-01).
Today we’re highlighting one of our saporin conjugates, Kisspeptin-SAP. This is a tool for eliminating cells that express the human and sheep G-protein coupled receptor, GPR54.
Kisspeptin is a ligand to GPR54 and functions in the hypothalamus, placenta, liver, pancreas, adipose tissue, bone, and limbic regions which shows the importance it can play in diagnosis and treatment of various disorders. It is one of the neuropeptides that governs the reproductive endocrine axis by regulating neuronal activity and secretion of hypothalamic gonadotropin releasing hormone (GnRH). GnRH is released from the hypothalamus to act on the anterior pituitary triggering the release of luteinizing hormone (LH), and follicle stimulating hormone (FSH). These gonadotropic hormones lead to sexual maturation and gametogenesis.
This is a 2023 publication using a Kisspeptin-saporin conjugate.
The objective of the authors was to test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells. They performed these tests using conjugates NKB-SAP and Kisspeptin-SAP.
The results showed that NKB-SAP ablated over 90% of the KNDy cells, while Kisspeptin-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval.
These findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.
Babatunde OO, Bibby MG, Atala A, Almeida-Porada G, Porada CD (2026) In utero HSC transplantation for sickle cell disease: A potential therapeutic approach that overcomes complications of current therapies. Prenat Diagn doi: 10.1002/pd.70142 PMID: 41936060
Objective: To examine current evidence and recent advances for treatment of sickle cell disease (SCD).
Summary: Biotinylated anti‐c‐kit/CD117 mAb coupled to a streptavidin‐conjugated saporin has been used to selectively deplete host HSC while preserving the host’s immune system. A single intravenous dose of the anti‐CD45‐saporin ADC enabled > 90% donor (congenic) hematopoietic engraftment and full correction of the SCD phenotype.
Serambeque B, Dias I, Mestre C, Marto CM, Botelho MF, Carvalho MJ, Laranjo M (2026) Photodynamic therapy-based strategies targeted at cancer stem cells: A scoping review. Cancers (Basel) 18(7):1162. doi: 10.3390/cancers18071162 PMID: 41976384
Objective: To examine strategies for targeting cancer stem cells using photodynamic therapy.
Summary: Photochemical internalization (PCI) is a widely adopted approach for targeting surface markers on cancer stem cells. Anti-CD133-SAP was evaluated in colorectal cancer, breast cancer, and melanoma. In CD133high colorectal cancer cells (WiDr), PCI with picomolar concentrations of AC133–saporin completely inhibited viability and colony formation, with no toxicity observed in the absence of light activation. Similar efficacy was observed in CD133+ breast (MDa-MB-231) and CD133high melanoma cells (FMEX-1) but not in CD133− breast cancer cells (MCF7), confirming target specificity. A similar strategy was employed to target CD44 in human cancer cell lines.
Cox TO, Devason AS, de Araujo A, Mason S, Subramanian M, Salvador AFM, Descamps HC, Kim J, Zhu Y, Litichevskiy L, Jung S, Song WS, Cortés-Martín A, Henderson NT, Huang KP, Nguyen T, Sae-Lee W, Umana IC, Sacta M, Rahman RJ, Wisser S, Nelson JAD, Golynker I, McSween AM, Hohmann EF, Patel S, Bub AL, Soekler C, Blank N, Hoxha K, Boccia L, Wong AC, Bahnsen K, Kim J, Biderman N, Abbasian D, Shoffler C, Petucci C, McAllister FE, Alhadeff AL, Fuccillo MV, Hill C, Jang C, Betley JN, de Lartigue G, Lee VY, Levy M, Thaiss CA (2026) Intestinal interoceptive dysfunction drives age-associated cognitive decline. Nature 652(8109):442-450. doi: 10.1038/s41586-026-10191-6 PMID: 41813891
Objective: To identify a mechanism by which inhibition of gut–brain signalling during ageing results in impaired neuronal activation in the hippocampus and loss of memory encoding.
Summary: The gastrointestinal microbiome has recently emerged as an important factor in the regulation of cognition and has been implicated as a modifiable peripheral signal that may contribute to age-associated memory loss. However, the circuits by which gut microbial signals are transmitted to the brain to modulate memory remain largely unclear. The authors evaluated CCKAR+ neurons to determine their role in cognitive decline.
Usage: CCK–SAP (IT-31) or Blank-SAP (IT-21) was injected (125 ng in 0.5 μl per ganglion).
Cardani S, Janes TA, Asif R, Pagliardini S (2026) Sex differences in the effects of etonogestrel on respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) 242(4):e70194. doi: 10.1111/apha.70194 PMID: 41823358
Objective: Chronic etonogestrel (ETO) treatment improved the CO2 chemoreflex in female rats in which <80% of chemoreceptor neurons comprising the retrotrapezoid nucleus (RTN) were eliminated. Since the progesterone receptor is widely expressed in both the male and female brain, authors investigated the effects of ETO on respiratory recovery.
Summary: Authors used SSP-SAP to partially eliminate RTN neurons. Dose-dependent impairment of the CO2 chemoreflex in both sexes following chemoreceptor lesion corroborates the findings that ETO treatment restores ventilation in female rats with moderate-sized lesions.
Usage: Four microinjections (150 nL per injection) were made with Substance P-conjugated saporin toxin (SSP-SAP, IT-11) and fluorescent carboxylate-modified Fluospheres TM to label injection sites.
Today we’re highlighting one of our saporin conjugates, Anti-CD117-SAP. This is a tool for depleting cells that express CD117, the tyrosine kinase growth factor receptor.
CD117 is expressed on hematopoietic stem cells, mast cells, and acute myeloid leukemia cells. Some of the areas where CD117 plays an essential role is in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance and mast cell development, migration and function.
Allogeneic hematopoietic stem cell transplantation can cure genetic diseases such as severe combined immunodeficiency (SCID), but it’s associated with significant toxicities such as graft-versus-host disease (GvHD). Using a patients’ own gene-modified hematopoietic stem and progenitor cells (HSPCs) can eliminate the risk of GvHD, but the treatment relies on gene transfer using viruses and genotoxic conditioning which carries risks.
The authors describe how base-editing is an alternative means to correct genetic defects while engineered virus-like particles (eVLPs) can deliver the base-edited proteins without the risks seen with viral integration.
In conclusion, transplantation of HSPCs that have been repaired through eVLP-mediated base-editing with CD117-ADC conditioning successfully reversed the SCID phenotype in mice, and highlights a significant advancement in disease treatment without the current toxicities.
We are highlighting one of our saporin conjugates, Neurotensin-SAP — a tool for depleting cells that express the neurotensin receptor (NTSR).
Neurotensin is a 13-amino-acid peptide found in the brain and spinal cord and is released by the hypothalamus. It is synthesized as part of a larger precursor protein that also includes the related neuropeptide neuromedin N. Neurotensin affects pituitary hormone release, interacts with the dopaminergic system, and is involved in vasodilation and hypotension. It can also modulate pain perception where intrathecal neurotensin has also been shown to be anti-nociceptive.
The objective was to determine whether NTSR1-expressing enteropancreatic neurons mediate the glucose-lowering effects of dietary olive oil and neurotensin, and to characterize their physiological role in glucose homeostasis.
The authors unilaterally injected neurotensin-SAP into the nodose ganglia to ablate NTSR1-expressing vagal neurons.
In their study, they demonstrated that neurotensin improves glucose tolerance by activating NTSR1-expressing enteropancreatic neurons, which connect the gut and pancreas. Ablation or disruption of these neurons abolished the glucoregulatory effects of both neurotensin and olive oil, establishing their necessity and sufficiency in this pathway.
Kozlíková M, Aukrust IKF, Rohlíčková M, Macháček M, Berg K, Weyergang A, Selbo PK (2026) Photochemical enhancement of PD-L1-SAP immunotoxin efficacy in non-small cell lung cancer cell lines. Front Immunol 17:1750003. doi: 10.3389/fimmu.2026.1750003 PMID: 41909645
Objective: To investigate photochemical internalization (PCI), a light–controlled endosomal escape technology, as a strategy to enhance intracellular delivery and efficacy of a PD–L1–targeted immunotoxin (anti–PD–L1–SAP).
Summary: Non–small cell lung cancer (NSCLC) cell lines with high (NCI–H1975) and low (A549) PD–L1 expression were subjected to PCI, resulting in a pronounced increase in cytotoxicity with picomolar potency (30 pM), while A549 cells required a higher dose (1000 pM) for a similar effect. PCI enhances delivery and activity of PD–L1–targeted biologics and may help overcome resistance mechanisms. Overall, PCI expands the therapeutic window of PD–L1–targeted immunotoxins and may complement current immunotherapies, supporting further preclinical evaluation in NSCLC.
Usage: Cells were then incubated with TPCS2a and anti-PD-L1-SAP (IT-45) for 18 h. The concentration of anti-PD-L1-SAP was 30, 100 and 1000 pM for NCI-H1975 cell line and 1000 pM for A549 cell line. BIgG-SAP (IT-74) was used as control.
Chen J, Xu T, Zhang C, Li L, He Y, Sun Z, He J, Yao Z, Cai P, Huang Y, Ye F, Guo W, Jia M, Qu J, Chen JF, Zhang Y (2026) 40 Hz light flickering alleviates chronic pain via adenosine signaling in the retina-amygdala pathway. Cell Res doi: 10.1038/s41422-026-01227-7 PMID: 41781500
Objective: To demonstrate the multifaceted therapeutic benefits of 40 Hz light flickering as a novel non-invasive approach for pain management and reveal a distinct retina-central amygdala circuit and adenosine signaling mechanism for control of chronic pain and pain memory
Summary: The authors examined the role of intrinsically photosensitive RGCs (ipRGCs). To selectively ablate ipRGCs, melanopsin-SAP was bilaterally injected into the vitreous humor. Treated mice displayed no significant change in baseline paw withdrawal threshold. Importantly, the antinociceptive effects of 40 Hz light flickering remained intact in both CFA and SNI models, despite ablation of ipRGCs. These results indicate that ipRGCs are not essential for the analgesia induced by 40 Hz light flickering.
Usage: Melanopsin-SAP (IT-44)) was bilaterally injected into the vitreous humor.
