The Generative Brain

ProFFIle (Predicting Fatal Familial Insomnia), JPND consortium

ProFFIle is a three year European research consortium funded through the EU Joint Programme Neurodegenerative Disease Research (JPND) 2021 call. Its aim is to find blood, urine and other easily sampled markers that predict when people who carry the FFI mutation (PRNP D178N) will become ill and how the disease progresses, so that prevention trials can be designed and monitored. It is coordinated by Roberto Chiesa at the Istituto di Ricerche Farmacologiche Mario Negri in Milan, not by CIC bioGUNE as one press report and earlier atlas text said. Partners are Goettingen University Medical Center, CIC bioGUNE, Hospital Universitario Araba, the Carlo Besta institute and Sabanci University, with total funding of 0.87 million euro. Family associations in Italy, Spain and Germany, AFIFF among them, helped collect longitudinal samples and spread the word. By the JPND final symposium in November 2024 the consortium reported a sample collection, candidate markers under validation, prion seeding tests tuned for urine, blood, nasal and tear samples, a mouse model and a blood-brain barrier chip model. No main results paper was found. Information only.

Status as of 2026-10-16. Please check the study registry for the latest position.

Key facts

  • ProFFIle stands for Prodromal biomarkers in fatal familial insomnia, a longitudinal study in humans and mice; JPND lists total funding of 0.87 million euro over 3 years.
  • The coordinator is Roberto Chiesa of the Istituto di Ricerche Farmacologiche Mario Negri, Milan, on the project sheet, the call results page, the 2024 symposium page and the poster.
  • A 2023 press article describes the project as led by Joaquin Castilla at CIC bioGUNE; the JPND sources list Castilla as a partner, so the press wording is treated as covering the Spanish arm only.
  • The six partner groups are Mario Negri (Chiesa), Universitaetsmedizin Goettingen (Inga Zerr), CIC bioGUNE (Castilla), Hospital Universitario Araba within the IIS Bioaraba institute (Izaro Kortazar), the Carlo Besta neurological institute (Fabio Moda) and Sabanci University, Istanbul (Nur Mustafaoglu).
  • ProFFIle came from the JPND 2021 call on linking pre-diagnosis disturbances of physiological systems to neurodegenerative diseases, which funded 14 projects with 15.5 million euro in total, announced in November 2021 and expected to start in early 2022.
  • National funders were the Italian Ministry of Health, the German Federal Ministry of Education and Research through DLR-PT, the Spanish Instituto de Salud Carlos III and Turkey's TUBITAK.
  • The planned cohort included FFI mutation carriers who were healthy when enrolled, among them people taking part in the DOXIFF doxycycline prevention trial.
  • The six work packages covered plasma NfL, GFAP and tau over time; PMCA and RT-QuIC seeding tests in blood, urine, olfactory mucosa and tear fluid; proteomics of brain-derived vesicles in plasma; proteomics and metabolomics of vesicles from iPSC-derived neurons; a new FFI mouse model; and an iPSC blood-brain barrier on a chip.
  • Preliminary results: seeding tests found FFI prions spiked into urine and plasma down to a 10 to the minus 12 dilution; 2 of 15 urine samples from carriers tested positive (one with symptoms, one without), all 17 control urines were negative, and one advanced-stage plasma sample was positive.
  • Five patient associations are named: AFIFF, the Italian A.I.En.P., the Spanish prion disease foundation, the German CJK-Initiative and A.I.G.S.S.; the consortium says they helped with ethics, awareness, dissemination and sample collection in Italy, Spain and Germany.
  • Researchers met patient associations, including AFIFF and the Spanish foundation FEEP, on 18 November 2023 at the FEEP annual convention.
  • Two papers acknowledge ProFFIle grants: a 2023 Basque FFI case series (Spanish code AC21_2/00032) and a 2025 Goettingen method for isolating brain-derived exosomes from blood (JPND2021-650-130).

Timeline

  1. 2021JPND announces 14 funded projects of the 2021 call, ProFFIle among them, coordinated by Mario Negri.
  2. 2022Projects of the call expected to start (early 2022 per the funder news); exact ProFFIle start date not published.
  3. 2022JPND publishes the ProFFIle project sheet (0.87 million euro, 3 years).
  4. 2023Basque FFI case series acknowledging the ProFFIle grant is published.
  5. 2023Consortium researchers meet patient associations at the FEEP annual convention in Spain.
  6. 2024Chiesa presents ProFFIle results at the JPND Final Symposium in Brussels (27 to 28 November); poster 29 presented by Carlo Besta.
  7. 2025Goettingen exosome isolation paper acknowledging the ProFFIle JPND grant is published.
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