Table 2.

Summary of studies using prion mutation or infections of organoids to date. N/a = not applicable.

Organoid protocol	PRNP mutation	Prion infection	Experimental timeframe	Key findings	Ref.
Spherical neural masses	Y218N	1Y218N and CJD2	Differentiated for 3, 6 or 9 weeks	PRNP Y218N neurons demonstrate hyperphosphorylation of Tau and neurofibrillary degeneration without evidence of misfolded PrP	(Matamoro s-Angles et al., 2018)
Cerebral organoids (Lancaster & Knoblich, 2014)	E200K 8-octerepe at insertion	N/a	110 days in culture	No pathological changes reported	(Gonzalez et al., 2018)
Cerebral organoids (Lancaster & Knoblich, 2014)	N/a	PRNP 129M/V organoids MV1 and MV2 subtype inoculums	5 months from starting differentiation to infection Up to 6 months to analysis	Organoids become infected with and propagate prions. PRNP 129M/V organoids showed a preference for propagation of the MV2 subtype but greater pathological changes associated with the MV1 subtype.	(Groveman et al., 2019)
Cerebral organoids (Lancaster & Knoblich, 2014)	E200K	N/a	Up to and including 1 year	No pathological changes reported	(Foliaki et al., 2020)
Cerebral organoids (Lancaster & Knoblich, 2014)	N/a	PRNP 129M/V organoids MV2 subtype inoculum	5 months from starting differentiation to infection Up to 4 months to analysis	Organoids could demonstrate the therapeutic efficacy of PPS3 when it was administered prophylactically, before, during and for a short time after infection, and therapeutically, administered after infection was established.	(Groveman et al., 2021)
Cerebral organoids (Lancaster & Knoblich, 2014)	E200K	N/a	Up to 10 months	Electrophysiological dysfunction with disturbed excitatory to inhibitory balance	(Foliaki et al., 2021)

¹Forebrain neuronal cultures only were tested for uptake of infection and found negative

²CJD type was not specified.

³Pentosan polysulfate