The Generative Brain

CHAPRION, pharmacological chaperones for genetic prion diseases (E-Rare JTC2014)

CHAPRION was a three country research project funded in the 2014 Joint Transnational Call of E-Rare, the European rare disease research funding network that later became part of EJP RD. It was coordinated by Jesus R. Requena through the Fundacion Ramon Dominguez and the Santiago health research institute, whose prion group sits at CIMUS, University of Santiago de Compostela, with partners at the University of Konstanz (Edward Malaga-Trillo) and the Mario Negri Institute in Milan (Roberto Chiesa). Its aim was to find small molecules that bind the normal prion protein (PrP) and hold mutant PrP in its native shape, so that it is less likely to misfold, as a possible drug class for genetic prion diseases such as GSS, FFI and genetic CJD, with tests in cells and animals. The European grant code is ERARE14-fp-097. A funding database excerpt suggests a start on 1 January 2015 for three years. No results report and no named chaperone compound from the project were found. The papers that credit the grant are mostly from the Milan and Trento side and include the FFI mouse doxycycline study. Information only, not medical advice.

Key facts

  • CHAPRION is one of 14 projects funded in the sixth E-Rare call (JTC2014), whose topic was innovative therapeutic approaches for rare diseases and whose total budget was about 10.8 million euro.
  • The JTC2014 call pooled 17 national funders, among them the German BMBF, the Italian Ministry of Health and the Spanish Instituto de Salud Carlos III; the EJP RD pages do not say which of them paid each CHAPRION partner.
  • The coordinator was Jesus Requena (Fundacion Ramon Dominguez, Instituto de Investigacion Sanitaria de Santiago, Spain), with partners Edward Malaga-Trillo (Universitat Konstanz, Germany) and Roberto Chiesa (Mario Negri Institute, Italy).
  • The stated aim was to stabilise the native single molecule form of mutant PrP with small ligands acting as pharmacological chaperones, raising the energy barrier to misfolding, using medicinal chemistry, biophysics, cell biology and animal efficacy tests.
  • The Santiago lead described the project before May 2018 as a multinational E-Rare funded effort to find chemical chaperones that stabilise normal PrP.
  • A funding database excerpt gives 149,988 euro over three years from 2015 for the Santiago share; this was not confirmed on an opened page.
  • The European grant code ERARE14-fp-097 CHAPRION is credited in four papers: a 2017 PLoS ONE cell study, two 2019 reviews and the 2021 FFI mouse study.
  • The 2021 Neurobiology of Disease study from Mario Negri, funded in part by CHAPRION, found that early doxycycline improved memory and circadian motor rhythm in FFI mice but did not delay onset, lower abnormal PrP or extend survival.
  • In the 2017 PLoS ONE paper, CHAPRION paid for one researcher in the Trento and Mario Negri team; the study, with a CIMUS co-author, showed that the antipsychotic chlorpromazine reduced prion replication in cells by moving PrP away from the cell surface rather than by binding it tightly.
  • A Bonn based DZNE author credits CHAPRION in two 2019 reviews, one co-written with the Mario Negri partner; the project page does not list a Bonn partner.
  • No paper crediting CHAPRION from the Santiago or Konstanz groups was found in Europe PMC, and no search hit was found for the ISCIII code AC14/00018.

Timeline

  1. 2014E-Rare Joint Transnational Call 2014 on innovative therapies for rare diseases; CHAPRION is among the 14 funded projects.
  2. 2015Reported start of the Santiago share of the project, for three years (search excerpt only).
  3. 2017PLoS ONE chlorpromazine paper crediting the E-Rare CHAPRION grant published.
  4. 2019Current Opinion in Pharmacology reviews by the Bonn and Milan authors and by the Trento group credit ERARE14-fp-097.
  5. 2019Viruses review on prion strain cell biology credits CHAPRION.
  6. 2021FFI mouse doxycycline study from Mario Negri, part funded by CHAPRION, published online.
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