Skip to main content

Letter in response to: “Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N acetylcysteine for paracetamol overdose—the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial”

Peer Review reports

As founders of PledPharma AB [1], including the main inventor of calmangafodipir [2], we have with great interest read the article entitled “Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose—the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial” published online by POP Trial Investigators and Dear [3] on January 8, 2019.

In the Background section of the article, POP Trial Investigators and Dear [3] state the following: “Calmangafodipir (Ca4Mn(DPDP)5) is a unique chemical species derived from mangafodipir, where 80% of the manganese in mangafodipir has been replaced with calcium. Based on the similarities between calmangafodipir and mangafodipir, it is anticipated that calmangafodipir would also exhibit SOD-dependent pharmacologic actions similar to those of mangafodipir”. We presume that they pertain the SOD-mimetic actions of these two compounds and not the SOD-dependent actions, as SOD is the admitted abbreviation of superoxide dismutases (intracellular and extracellular enzymes). Unfortunately, POP Trial Investigators and Dear have omitted an essential reference written by us and Torsten Almén (deceased January 8, 2016) [1]. This article describes the background of both calmangafodipir and mangafodipir, and their SOD-mimetic properties, so the word “anticipated” is highly misleading. The article by Brurok et al. [4] (reference 10 in POP Trial Investigators and Dear [3]) is interesting but it was published 13 years before calmangafodipir was described in a scientific journal [5]. You can find our article [1] on the sponsor’s website (https://www.pledpharma.com/pipeline/publications/), and as the title reads “Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties” there should be no doubt that this is the most appropriate reference to cite. The omission, whether deliberate or not, is a disservice to the reader. Furthermore, we believe that the earlier “original” work is actually the work that led to Dear’s clinical trial study.

Availability of data and materials

Not applicable.

References

  1. 1.

    Karlsson JOG, Ignarro LJ, Lundström I, Jynge P, Almén T. Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties. Drug Discov Today. 2015;20:411–21.

    CAS  Article  Google Scholar 

  2. 2.

    Karlsson J, Reineke K, Kurz T, Andersson R, McLaughlin C, Jacobsson S, Näsström J. Calmangafodipir, a new chemical entity, and other metal complexes, method of preparation, compositions, and methods of treatment. US 9187509 B2. Nov 17, 2015.

  3. 3.

    POP Trial Investigators, Dear J. Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose—the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial published study protocol for a randomised controlled trial. Trials. 2019;20(1):27. https://doi.org/10.1186/s13063-018-3134-1.

    Article  Google Scholar 

  4. 4.

    Brurok H, Ardenkjaer-Larsen JH, Hansson G, Skarra S, Berg K, Karlsson JO, Laursen I, Jynge P. Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties? Biochem Biophys Res Commun. 1999;254:768–72.

    CAS  Article  Google Scholar 

  5. 5.

    Karlsson JOG, Kurz T, Flechsig NJ, Andersson RGG. Superior therapeutic index of calmangafodipir in comparison to mangafodipir as a chemotherapy adjunct. Transl Oncol. 2012;5:492–502.

    Article  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Affiliations

Authors

Contributions

All authors read and approved the final manuscript.

Authors’ information

Not applicable.

Corresponding author

Correspondence to Jan Olof G. Karlsson.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

JOGK owns shares in PledPharma AB and is the main inventor of calmangafodipir (owned by PledPharma AB). IL owns shares in PledPharma AB. PJ and LJI have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Karlsson, J.O.G., Jynge, P., Lundström, I. et al. Letter in response to: “Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N acetylcysteine for paracetamol overdose—the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial”. Trials 20, 380 (2019). https://doi.org/10.1186/s13063-019-3476-3

Download citation