Autophagy induction (rapamycin) and IVIG in the Tg(PrP-A116V) GSS mouse model, University of Chicago multi-targeted therapy program

Two preclinical studies in the Tg(PrP-A116V) mouse, a transgenic model of Gerstmann-Straussler-Scheinker disease (GSS), tested repurposed approved drugs: rapamycin to induce autophagy (University of Chicago, 2012) and intravenous immunoglobulin (IVIG; Indiana University with Mastrianni as co-author, 2019). Both delayed onset modestly, by roughly 10 to 18 percent for rapamycin and about 11 percent for IVIG, and neither is shown to help after onset. A 2025 conference talk by Mastrianni carries the title "multi-targeted approach", but its content was not read. Information only; mouse evidence, no human data, not medical advice.

Key facts

  • In the 2012 study, rapamycin was injected intraperitoneally at 10 or 20 mg/kg three times a week from 6 weeks of age in Tg(PrP-A116V) mice, with mean onset of 134 days for vehicle, 149 days at 10 mg/kg and 159 days at 20 mg/kg.
  • Only the 20 mg/kg rapamycin dose significantly extended survival, with mean age at death of 189 days versus 173 days for vehicle.
  • Rapamycin raised the autophagy marker LC3-II, lowered insoluble mutant PrP and almost abolished plaques, yet ataxia still occurred, so the authors concluded plaques are not essential for the GSS phenotype.
  • Rapamycin treatment increased glial apoptosis, mostly in astrocytes; the 2012 work was funded by NINDS grant R01 NS051480.
  • A commentary on the 2012 paper lists group sizes of 17, 25 and 20 mice and warns that rapamycin is immunosuppressive and that doses scaled to humans would be well above transplant doses.
  • In the 2019 study, IVIG at 20 mg/kg weekly from day 90 pushed mean onset from 116.9 to 130.2 days (about 11 percent) and mean death from 179 to 191 days, with 34 mice per group.
  • IVIG lowered cerebellar plaque burden and neuronal apoptosis at 120 days, but these differences were absent at the terminal stage, and survival after onset was not significantly extended.
  • The 2019 IVIG study was funded by the Baudrand Research Foundation, led from Indiana University School of Medicine, and the authors attribute the modest effect to poor brain penetration; the mechanism was not tested.
  • Histology in the IVIG paper used only 3 animals per group, and the authors note internal inconsistencies in the stated onset delay.
  • Mastrianni is listed with a talk titled "A Multi-Targeted Approach in Search of Prion Disease Therapy" on the CJD Foundation 2025 presentations page; no abstract is given.
  • The CJD Foundation Family Conference ran 11 to 13 July 2025 in Chicago; the link of the talk to that event comes from a search excerpt.

Timeline

  1. 2012Cortes et al. publish rapamycin delaying onset and preventing plaques in Tg(PrP-A116V) mice (J Neurosci).
  2. 2018IVIG GSS mouse paper published online; print issue April 2019 (Mol Neurobiol 56:2353).

Last checked 1 November 2026

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