The Generative Brain

AGL2017-88353-P, bioassay of Spanish sporadic CJD and VPSPr cases in ovine and caprine PrP transgenic mice (IRTA-CReSA)

AGL2017-88353-P is a Spanish state funded project announced by IRTA on 15 January 2018 under the title "Study of a possible causal relationship between cases of sporadic Creutzfeldt-Jakob disease and scrapie of small ruminants". The design runs the zoonosis question backwards. Instead of putting sheep prions into mice carrying human prion protein, which is what the 2014 Nature Communications study from Toulouse did, it takes human brain material from five Spanish cases, three sporadic CJD cases diagnosed in Catalonia of the MM1, MV2 and VV2 subtypes and two VPSPr cases diagnosed in the Basque Country, and inoculates it serially into two transgenic mouse lines that express sheep and goat prion protein, Tg338 carrying VRQ and Tg501 carrying ARQ, with neuropathological and biochemical characterisation of whatever strain emerges and protein misfolding cyclic amplification in small ruminant substrates as a faster parallel route. The logic is that if a sporadic case began as a small ruminant agent, the agent may be recoverable in a small ruminant host. Nothing opened reports a result. Searches of Europe PMC on the grant number, on the grant identifier field, on the two mouse line names combined with sporadic CJD and VPSPr terms, on the IRTA prion author with human prion terms, and on the centre affiliation with VPSPr terms returned no publication of this bioassay as of 17 October 2026. The IRTA news item, last modified on 6 November 2024, still reads as an announcement with no outcome, and no later IRTA prion news item reports on it. So the honest state of this entity is a funded and ethically approved design with named partners and no evidenced output. Information only, not medical advice.

Status as of 2026-10-17. Please check the study registry for the latest position.

Key facts

  • The project reference is AGL2017-88353-P and the funder is the Spanish State Programme for the Promotion of Research, Scientific and Technical Excellence, knowledge generation subprogramme, within the state plan for scientific and technical research and innovation of the Ministry of Economy and Competitiveness, at a 56 percent funding share. No total amount, start date or end date is given.
  • The human material is five cases: three sporadic CJD cases of the MM1, MV2 and VV2 subtypes diagnosed in Catalonia, and two VPSPr cases of the MM and MV genotypes diagnosed in the Basque Country.
  • The animal models are two transgenic mouse lines expressing small ruminant cellular prion protein, Tg338 with the VRQ allele and Tg501 with the ARQ allele. The method is serial intracerebral inoculation followed by neuropathological and biochemical characterisation of the resulting strains.
  • A second strand uses protein misfolding cyclic amplification in small ruminant substrates, presented as a faster in vitro route to adapt the human agents to a small ruminant host before in vivo characterisation.
  • The work is run from the PRIOCAT laboratory and the IRTA-CReSA biocontainment unit, described as level 3 facilities inside the national high biological safety laboratory network, and was approved by the IRTA animal ethics committee and the UAB biosafety committee.
  • Named collaborating institutions are HUB-ICO-IDIBELL, CIC bioGUNE, CISA-INIA, INRA and the UAB veterinary faculty, each represented by a named researcher in a public professional role.
  • The stated basis is the December 2014 Nature Communications paper from the Toulouse INRA ENVT group, which reported that a panel of sheep scrapie isolates transmitted to transgenic mice overexpressing human prion protein at an efficiency comparable to cattle BSE, and that serial passage produced prions phenotypically identical to those of sporadic CJD. The authors of that paper state the finding raises the question of a link rather than proving one.
  • The inverse direction had already been shown to work before 2018: a February 2016 Acta Neuropathologica Communications paper from INRA Jouy-en-Josas transmitted human MM2-cortical sporadic CJD prions into mice overexpressing the ovine VRQ PrP allele, where the agent shifted abruptly on second passage into two strain variants with different biochemistry and tissue tropism.
  • No publication of the bioassay was found. A Europe PMC phrase search on the grant number and a search of the grant identifier field both returned zero records; a search combining the Tg338 and Tg501 line names with sporadic CJD and VPSPr terms returned 46 records, none of which is this study; a search on the IRTA prion author with human prion terms returned 21 records, of which the only human prion paper is a 2019 CSF neurogranin study where the centre is one affiliation among many.
  • A search of the centre affiliation and the same author with VPSPr terms returned four records, all animal or rodent prion model papers from 2017 to 2026 and none reporting human case transmission. The two earlier searches carried over from the IRTA-CReSA order reach the same negative conclusion from a different angle.
  • The IRTA news feed holds seven prion related items, including later items on dog prions, on the origin of BSE and on a cerebrospinal fluid marker for human prion disease, but no follow-up item on this project.
  • Public information about the people involved is limited to the roles named in the IRTA announcement. One named collaborator, the Bellvitge neuropathologist, is already an entity in the atlas and is the human neuropathology side of the design.

Timeline

  1. 2014Nature Communications paper from the Toulouse group reports evidence for zoonotic potential of ovine scrapie prions in mice overexpressing human prion protein, the result the project cites as its starting point.
  2. 2016Acta Neuropathologica Communications paper from INRA Jouy-en-Josas transmits human MM2-cortical sporadic CJD prions into ovine VRQ PrP overexpressing mice and finds a strain split on second passage.
  3. 2018IRTA publishes the announcement of project AGL2017-88353-P, with the five human cases, the two mouse lines, the PMCA strand, the named partners and the ethics and biosafety approvals.
  4. 2024The IRTA announcement page is last modified and still carries no result.
  5. 2026Six Europe PMC searches and the IRTA news feed find no publication, abstract or news item reporting an outcome of the bioassay.