The Generative Brain
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan logo

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan

The Mario Negri Institute is a private, non-profit Italian research foundation opened in Milan in 1963 with the bequest of Mario Negri, recognised by the Ministry of Health as an IRCCS since 2013, with sites in Milan, Bergamo and Ranica and about 600 staff. It does not patent its research and takes no more than 10 percent of its budget from any single source. For prion disease it matters in three ways. It is the registered sponsor of the Telethon funded doxycycline prevention trial in people at risk of fatal familial insomnia (2011 to 2024, no results posted). Its Neuroscience Department, headed by Gianluigi Forloni, hosts a Laboratory of Prion Neurobiology led by Roberto Chiesa that builds genetic prion disease mouse models and tests anti-prion compounds. And in 2026 it is promoting a biobank of samples from people at family risk of FFI with the Treviso hospital, co-funded by the family association AFIFF.

Key facts

  • The institute opened its first Milan site on 1 February 1963 with 21 researchers, funded by the bequest of the jeweller and philanthropist Mario Negri, and describes itself as a private foundation devoted entirely to research.
  • The Ministry of Health has recognised it as an IRCCS since 2013; Giuseppe Remuzzi has been director since 1 July 2018, succeeding Silvio Garattini (director 1963 to 2018), who is named as president.
  • It has about 600 staff in 10 research departments and 58 laboratories across Milan, Bergamo and the Ranica rare disease centre opened in 1992.
  • It has not patented its research for more than 50 years, and it accepts no more than 10 percent of its annual budget from a single source; in 2025 it reported 209 active projects and 418 publications.
  • The Neuroscience Department, headed by Gianluigi Forloni, includes a Laboratory of Prion Neurobiology and lists prion projects funded by Telethon (DOXIFF), the EU JPND (ProFFIle), the Ministry of Health (RF-2016-02362950) and the CJD Foundation (prion vaccines in mice).
  • Both trial registries name Mario Negri as sponsor of the doxycycline prevention trial in people at risk of FFI, with Fondazione Telethon as funder or collaborator; it started on 28 April 2011, completed on 30 November 2024 with 29 enrolled, and no results are posted.
  • Mario Negri scientists led the published account of the trial, a study designed jointly with an at-risk family that chose not to learn their genotype.
  • Mario Negri researchers co-authored the phase 2 doxycycline trial in CJD (121 patients in Italy and France), which found no survival benefit.
  • Its prion laboratory built a transgenic FFI mouse that developed sleep and neurological disease without detectable infectious prions (PLoS Pathogens 2015), with Telethon funding.
  • In the FFI mouse, presymptomatic doxycycline restored memory and circadian motor rhythm but did not prevent terminal disease; the work was funded by Ministry of Health grant RF-2016-02362950, the E-Rare CHAPRION project and Telethon.
  • The prion laboratory identified a zinc porphyrin that both lowers native prion protein and blocks propagation of several prion strains (iScience 2023), and received CJD Foundation grants in 2016 and 2019 for this compound line, including brain delivery by nanoparticles.
  • A 2026 Acta Neuropathologica paper from Mario Negri with ISS, NIAID Rocky Mountain Laboratories, UKE Hamburg and CIC bioGUNE co-authors found that the D178N mutation gives RML prions new strain properties that do not mimic human genetic prion disease; it was funded by RF-2016-02362950.
  • A Europe PMC index lists 64 prion or PrP papers with Roberto Chiesa and a Mario Negri affiliation from 1997 to 2026, including the 2019 Neurology analysis of age at onset for preventive trial design with Eric Minikel.
  • In 2026 the institute is promoting a three-year biobank of samples from people at family risk of FFI, with the Treviso Ca Foncello hospital as a site and an 8,500 euro contribution from AFIFF.
  • Forloni and Chiesa sit on the AFIFF scientific committee.

Timeline

  1. 1963First Milan site opens with 21 researchers.
  2. 1984Bergamo site opens.
  3. 1992Ranica rare disease clinical research centre opens.
  4. 2007Milan headquarters moves to Bovisa.
  5. 2011Sponsored doxycycline prevention trial in people at risk of FFI starts.
  6. 2012Prion laboratory Neuron study on mutant PrP and calcium channel traffic reported.
  7. 2013Recognised as an IRCCS by the Ministry of Health.
  8. 2014Phase 2 doxycycline trial in CJD published with Mario Negri co-authors.
  9. 2015Transgenic FFI mouse model published in PLoS Pathogens.
  10. 2016CJD Foundation grant to the prion laboratory for an anti-prion compound.
  11. 2018Giuseppe Remuzzi becomes director.
  12. 2019CJD Foundation grant for nanoparticle brain delivery of the porphyrin.
  13. 2021Doxycycline FFI mouse study published.
  14. 2022Prion paper on the FFI prevention trial and public engagement.
  15. 2023Dual-action anti-prion porphyrin published in iScience.
  16. 2024FFI doxycycline trial completion date in the registry; no results posted.
  17. 2026D178N RML prion strain paper published in Acta Neuropathologica.
  18. 2026Biobank project with AFIFF announced.
  19. 2026Treviso hospital joins the Mario Negri FFI biobank study.
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