Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai (Doh-ura laboratory, prion therapeutics)

Key facts

• The Department of Neurochemistry at Tohoku University Graduate School of Medicine, Sendai, is the stated affiliation of the group on papers from 2014 to 2022.
• The 2016 PLoS Pathogens paper reported that one injection of selected cellulose ethers greatly extended survival in rodents infected with hamster prions, with benefit falling once symptoms had begun; safety was not evaluated and the mechanism is unresolved.
• Itoham Foods and Tohoku University hold a patent on cellulose ether medicinal chemicals with Doh-ura as inventor, and Itoham was also a funder of the 2016 study.
• A 2021 paper with Case Western Reserve University, the National Prion Disease Pathology Surveillance Center, Jilin University and USDA found that one TC-5RW dose at inoculation extended survival of infected transgenic mice (about 170 versus 72 days), with skin seeding activity undetectable by two assays; groups were small and the authors call it proof of concept.
• The 2021 paper was funded in part by Japan Society for the Promotion of Science grants to Teruya and Doh-ura and an AMED grant to Doh-ura, alongside CJD Foundation and NIH money on the US side.
• In 2014 the lab screened 38 commercial glycoside compounds in infected cells; the lead (Gly-9) cut abnormal prion protein across three strains but gave only marginal survival benefit in mice.
• A 2017 screen of natural materials found melanin-like material lowered abnormal prion protein in cells, but it did not work in a cell-free assay or in mice, so the authors judged it unlikely to matter for disease.
• A 2022 review by Teruya and Doh-ura concluded that brain delivery of anti-prion polymers is still a challenge, though polymers remain useful as leads and as tools for studying PrPSc structure.
• In the 2020 Nucleic Acids Research paper on PrP-lowering antisense oligonucleotides, Doh-ura is the only Tohoku author; the paper's author contributions suggest he supplied infected material for the Fukuoka-1 and 22L strains (inference, not stated outright).
• The Japanese pentosan polysulfate patient series (11 patients from 2004, mean survival after treatment 24.2 months, no clear improvement) was led from Fukuoka University with Doh-ura as a co-author.
• The 2002 Japanese quinacrine report came from Fukuoka University authors and did not include Doh-ura; his own quinacrine-related writing is known only from search excerpts.
• Search profiles list Doh-ura as professor in the Neurochemistry department under a longer Center for Prion Research style name; this is unconfirmed.

Timeline

1. 2004Doh-ura and colleagues publish intraventricular drug infusion work in animal models (Journal of Virology), with the Kyushu-era affiliation recorded in the existing pentosan entity.
2. 2004Fukuoka University begins intraventricular PPS in patients; Doh-ura later co-authors the report.
3. 2009Tsuboi, Doh-ura and Yamada publish the 11-patient Japanese PPS series.
4. 2014Nishizawa et al. publish the glycoside compound screen from the Tohoku department.
5. 2016Teruya et al. publish the cellulose ether rodent protection study.
6. 2017Hamanaka et al. publish the melanin screen with Tokushima University.
7. 2020Minikel et al. publish PrP-lowering antisense results with Doh-ura as a Tohoku co-author.
8. 2021Ding et al. publish the TC-5RW skin seeding study with US and Chinese partners.
9. 2022Teruya and Doh-ura publish the polymer review online.