ArticleThe Journal of clinical investigation2012
A botulinum toxin-derived targeted secretion inhibitor downregulates the GH/IGF1 axis.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Expert consensus document: A consensus on the medical treatment of acromegaly.Nature reviews. Endocrinology · 2014Guideline
- Evolution of botulinum neurotoxin serotype X proteases to induce inflammatory cell death in cancer cells.Nature biotechnology · 2026Article
- Characterisation of the SNAP-25 and SNAP-23 cleavage properties of the botulinum neurotoxin-like protein from Enterococcus.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Prolactin and oxytocin: potential targets for migraine treatment.The journal of headache and pain · 2023Review
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- Exosomal RNAs in the development and treatment of pituitary adenomas.Frontiers in endocrinology · 2023Review
- Harnessing the Membrane Translocation Properties of AB Toxins for Therapeutic Applications.Toxins · 2021Review
- Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021Review
- Article
- New Engineered-Botulinum Toxins Inhibit the Release of Pain-Related Mediators.International journal of molecular sciences · 2019Article
- Botulinum and Tetanus Neurotoxins.Annual review of biochemistry · 2019Review
- Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity.Toxins · 2018Review
- Review
- Neuronal entry and high neurotoxicity of botulinum neurotoxin A require its N-terminal binding sub-domain.Scientific reports · 2017Article
- Association of circulating dipeptidyl-peptidase 4 levels with osteoporotic fracture in postmenopausal women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Article
- Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells.Oncotarget · 2016Article
- Pasireotide: a novel treatment for patients with acromegaly.Drug design, development and therapy · 2016Review
- Tomosyn Negatively Regulates Arginine Vasopressin Secretion in Embryonic Stem Cell-Derived Neurons.PloS one · 2016Article
- Structural analysis of Clostridium botulinum neurotoxin type D as a platform for the development of targeted secretion inhibitors.Scientific reports · 2015Article
- Treatment of Acromegaly: Are We Satisfied With the Current Outcome?EBioMedicine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Botulinum neurotoxins (BoNTs) are zinc endopeptidases that block release of the neurotransmitter acetylcholine in neuromuscular synapses through cleavage of soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein receptor (SNARE) proteins, which promote fusion of synaptic vesicles to the plasma membrane. We designed and tested a BoNT-derived targeted secretion inhibitor (TSI) targeting pituitary somatotroph cells to suppress growth hormone (GH) secretion and treat acromegaly. This recombinant protein, called SXN101742, contains a modified GH-releasing hormone (GHRH) domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-LHN/D, where HN/D indicates endopeptidase and translocation domain type D). In vitro, SXN101742 targeted the GHRH receptor and depleted a SNARE protein involved in GH exocytosis, vesicle-associated membrane protein 2 (VAMP2). In vivo, administering SXN101742 to growing rats produced a dose-dependent inhibition of GH synthesis, storage, and secretion. Consequently, hepatic IGF1 production and resultant circulating IGF1 levels were reduced. Accordingly, body weight, body length, organ weight, and bone mass acquisition were all decreased, reflecting the biological impact of SXN101742 on the GH/IGF1 axis. An inactivating 2-amino acid substitution within the zinc coordination site of the endopeptidase domain completely abolished SXN101742 inhibitory actions on GH and IGF1. Thus, genetically reengineered BoNTs can be targeted to nonneural cells to selectively inhibit hormone secretion, representing a new approach to treating hormonal excess.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.