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Mambaquaretin: therapeutic as well as diagnostic uses?

New work by the CEA-Joliot on the venom of the green mamba confirms the therapeutic potential of the toxin and paves the way for its use as a diagnostic tool.

Published on 9 December 2020

The green mamba is a highly aggressive venomous snake found on the African continent. A few years ago, a team from the CEA-Joliot discovered a very minor toxin in the green mamba’s venom, known as mambaquaretin. This peptide has the property of blocking the V2R vasopressin receptor, a renal receptor that plays a key role in the regulation of water balance. Mambaquaretin, which is highly selective for V2R, is a potential therapeutic candidate for the treatment of kidney disorders such as hyponatremia or polycystic kidney syndrome, a rare disease.

Several teams from the CEA-Joliot have come together to further characterize the pharmacology of mambaquaretin and evaluate its efficacy in treating hyponatremia, a disease that leads to a lack of sodium in the blood as a result of excessive dilution. The researchers worked with an animal model of hyponatremia using desmopressin (DDAVP), an antidiuretic drug commonly utilized to treat disorders in which the kidneys are unable to retain water. They monitored the biodistribution of mambaquaretin by positron emission tomography and showed that it targets the kidneys, which express a very high number of V2Rs. It also proves to be non-toxic, even at high doses.

In addition, the scientists synthesized a fluorescent mambaquaretin and showed that it can be used as an imaging probe in renal tumor cell lines known to abnormally express V2R on their surface.

Frédéric Joliot Institute for Life Sciences - CEA Paris-Saclay
Humana Biosciences, Prologue Biotech, Labège
Center for Interdisciplinary Research in Biology, Paris - Inserm
​IGF, Montpellier - Inserm

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