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In pursuing their work on mambaquaretin, SIMoS researchers conducted a collaborative study confirming the therapeutic potential of the toxin and paving the way for its use as a diagnostic tool. The study was published in Theranostics.
A few years ago, a SIMoS team discovered and characterized a very minor toxin of green mamba venom, mambaquaretin (news from 23 May 2017). This 57-residue peptide has antagonistic activity on the vasopressin type 2 receptor (V2R), which plays a key role in regulating water reabsorption at the kidney collecting tube. Highly selective for V2R, mambaquarétine is a potential therapeutic candidate for the treatment of renal function disorders such as hyponatremia or polycystic kidney disease, a rare disease.
In a study published in Theranostics, in collaboration with teams from SPI and SHFJ, the SIMoS team has further characterized the pharmacology of mambaquaretin and evaluated its efficacy in the treatment of hyponatremia. The researchers show that, in rats, mambaquaretin is very effective in preventing hyponatremia induced by a specific V2R agonist, dDAVP, at low doses. They evaluated the pharmacokinetics, pharmacodynamics, biodistribution and excretion of the molecule in vivo, primarily using positron emission tomography (PET) imaging. Conclusions ? The biodistribution of mambaquaretin decreases in the kidneys and blood in the same way, according to a biphasic curve, indicating that the molecule targets the kidneys, which express a very high number of V2Rs. The authors believe that the therapeutic index of mambaquaretin is very high: at even the highest doses, at which they observe benefits for model animals, they never observe any signs of toxicity of the molecule.
Finally, the authors have synthesized two fluorescent versions of mambaquaretin. After confirming that these two fluorescent molecules bind well to V2R, with an affinity roughly comparable to that of mambaquaretin, they used them as imaging probes on renal tumor cell lines known to ectopically express V2R on their surface. Their preliminary results indicate that labeled mambaquaretin could be used as a probe to identify cancers that express V2R, paving the way for further exploitation of this toxin as a theranostic agent.
Nicolas Gilles (email@example.com)
A snake toxin as a theranostic agent for the
type 2 vasopressin receptor. | Theranostics, 2020; 10(25):11580-11594
Droctové, M. Lancien, V. L. Tran, M. Susset, B. Jego, F. Theodoro, P. Kessler,
G. Mourier, P. Robin, S. Siramakan Diarra, S. Palea, A. Flahault, A. Chorfa, M.
Corbani, C. Llorens-Cortes, B. Mouillac, C. Mendre, A. Pruvost, D. Servent, C. Truillet, N. Gilles
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.