The Generative Brain

Linkoping University, IFM chemistry, luminescent conjugated oligothiophene group (Nilsson and Hammarstrom)

Two closely linked research groups in the Division of Chemistry of the Department of Physics, Chemistry and Biology (IFM) at Linkoping University, Sweden, are the source of the luminescent conjugated oligothiophenes (LCOs), small thiophene-based fluorescent molecules whose colour changes with the shape of the protein aggregate they bind. The chemistry side is the Laboratory of Multidisciplinary Applied Chemistry led by Professor Peter Nilsson; the protein misfolding side is the Hammarstrom Lab led by Professor Per Hammarstrom, which has run a dedicated prion safety laboratory since October 2005. Working with Adriano Aguzzi's Zurich Institute of Neuropathology, where Nilsson did his postdoc, the groups used these molecules to tell prion strains apart in tissue (2007), introduced the pentameric LCOs including pFTAA (2009), and showed that pFTAA and related polythiophenes slow prion propagation in cells and prolong survival in infected mice (2012, 2015). pFTAA is the compound behind the 2017 EU orphan designation NSC500 for CJD, held by an Austrian company that no source read links to Linkoping. Since about 2016 the groups' own lead papers have moved mostly to Alzheimer, tau and alpha-synuclein, with prion work continuing as co-authorship on studies led from UC San Diego and Calgary. This is laboratory research with mouse and tissue data; no LCO is a clinical test or treatment for CJD. Information only, not medical advice.

Key facts

  • The Laboratory of Multidisciplinary Applied Chemistry, led by Professor Peter Nilsson in IFM Chemistry, designs and makes thiophene-based fluorescent ligands for diagnostics, therapeutics and research tools, including ligands that detect and tell apart disease-associated protein aggregates and theranostic concepts pairing them with clearance agents.
  • Nilsson took his PhD at IFM in 2005, was a postdoc in Adriano Aguzzi's Zurich group where he explored LCOs as fluorescent ligands for prion diseases including BSE and CJD, returned to Linkoping in 2008 to start his own group and became professor of organic chemistry in 2015.
  • The Hammarstrom Lab studies protein misfolding in amyloidoses and prion disease, works with the prion protein, and studies prion strains including the Norwegian chronic wasting disease strain by cell-free replication; a dedicated prion safety laboratory was inaugurated for the group in October 2005.
  • A 2007 Nature Methods paper by the Zurich and Linkoping groups showed that conformation-sensitive luminescent conjugated polymers could tell apart four mouse-passaged prion strains that looked identical by standard immunohistochemistry, and separate BSE field isolates from a related bovine disease.
  • The 2009 ACS Chemical Biology paper, first author at IFM Chemistry Linkoping with Hammarstrom and Nilsson as last authors and Aguzzi among co-authors, introduced pentameric LCOs; one of them, p-FTAA, distinguished deposits of two mouse prion strains ex vivo and labelled amyloid-beta and tau lesions.
  • In 2012 the Zurich and Linkoping groups reported that pFTAA and related polythiophenes reduce prion infectivity in a cell assay by over-stabilising prion aggregates; in 2015 a Zurich, ETH, Linkoping and Lyon study with five IFM Linkoping authors including Hammarstrom, Nystrom and Nilsson showed that polythiophenes with at least five rings and regularly spaced carboxyl groups prolonged survival of prion-infected mice, the designed lead by more than 80 percent.
  • Hammarstrom's group also works on the human prion protein itself: a 2012 J Biol Chem study found that changing codon 129 of recombinant human PrP altered amyloid fibril formation, and the authors call position 129 a key site for recruitment into the amyloid state.
  • Later prion papers with Linkoping co-authors are mostly led elsewhere: UC San Diego studies on prion spread after intravenous challenge (2018) and on PrP glycans and fibril formation (2020), and a Calgary study (online September 2020) in which pFTAA with spectral microscopy detected prion deposits in mice before clinical signs, with sensitivity the authors compare to RT-QuIC, funded in part by the Swedish Research Council.
  • A Europe PMC query returned 91 records by Hammarstrom or Nilsson matching prion terms; the groups' own lead papers after 2015 are mainly on Alzheimer, tau and alpha-synuclein, and the current group pages list no prion-specific paper in 2024 to 2026 apart from co-authored work.
  • Nilsson's staff page names two spin-off companies commercialising group findings, Ebba Biotech AB and Celluminova AB, and lists funders including the ERC, the Swedish Research Council, the Swedish Foundation for Strategic Research, NIH and JPND, without years or amounts. Ebba Biotech sells Amytracker protein aggregate stains from Solna, but its homepage does not mention Linkoping, LCOs or prions.
  • In a January 2023 university news item, Nilsson said the team had molecules it wanted to develop for diagnosis, possibly as PET tracers, and estimated testing within 5 to 10 years; the item concerns Alzheimer disease and does not mention prions.

Timeline

  1. 2005Prion safety laboratory inaugurated for the Hammarstrom group.
  2. 2007Nature Methods paper: luminescent conjugated polymers discriminate prion strains (Zurich and Linkoping).
  3. 2008Nilsson returns from the Zurich postdoc and starts his own group at Linkoping.
  4. 2009ACS Chemical Biology paper introduces pentameric LCOs including p-FTAA.
  5. 2010J Neurosci paper, Nilsson first author, on selective interactions between co-infecting prion strains.
  6. 2012J Biol Chem paper: polythiophenes including pFTAA inhibit prion propagation.
  7. 2012J Biol Chem paper on codon 129 substitutions in human PrP fibrillation.
  8. 2015Nilsson becomes professor of organic chemistry.
  9. 2015Science Translational Medicine paper: polythiophenes as antiprion compounds in mice.
  10. 2017EU orphan designation EU/3/17/1883 granted to NeuroScios GmbH for pentamer formyl thiophene acetic acid in CJD; no link to Linkoping stated.
  11. 2020Calgary and Linkoping paper on early prion deposit detection with pFTAA published online.
  12. 2023University news item on Nilsson's tracer molecules and diagnostic plans for Alzheimer disease.
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