. Author manuscript; available in PMC: 2023 Oct 19.

Published in final edited form as: Nat Biomed Eng. 2023 Jan 12;7(4):370–386. doi: 10.1038/s41551-022-00987-y

Table 3. iPSC-based and ESC-based therapies for neurological disorders.

Disease	Cell source	Stage	Key findings
Traumatic brain injury (TBI)	iPSC	Preclinical	A combination of iPSC-derived neural precursor cells and environmental enrichment substantially rescued cognitive deficits in a rat model of TBI¹⁸⁹.
Traumatic brain injury (TBI)	iPSC	Preclinical	Transplantation of iPSC-derived neural precursors improved social behavioural deficit in a mouse model of TBI¹⁹⁰.
Spinal cord injury (SCI)	iPSCs	Phase I/II	On the basis of the efficacy and safety observed in rodent^191,192 and non-human primate¹⁹³ models of SCI, a clinical trial to assess iPSC-derived neural precursors is in the pipeline¹⁹⁴.
	ESC	Phase I/II	Human ESC-derived oligodendrocytes improved motor function in rodent SCI models in the absence of serious adverse effects^195–197.
	ESC	Phase I/II	Preliminary clinical outcomes have displayed signs of safety and efficacy (NCT02302157), but follow-up and full clinical data are not yet available¹⁹⁸.
Macular degeneration	iPSC	Phase I/II clinical trials	On the basis of the efficacy and safety shown after transplanting iPSC-derived retinal pigmented epithelium into rodents and mammals¹⁹⁹, two Phase-I/II clinical trials are underway to assess the safety of iPSC-derived retinal pigmented epithelial transplants in patients with age-related macular degeneration^200,201.
Macular degeneration	ESC	Phase I/II	The grafting of ESC-derived-retinal pigmented epithelial cells has led to the rescue of some visual aspects in clinical trials^102,201,202. However, this has not been recapitulated in other clinical studies²⁰³.
Amyotrophic lateral sclerosis (ALS)	iPSC	Preclinical	iPSC-derived neural precursors have been shown to improve their phenotype in wild-type ALS²⁰⁴ and in SOD-1 mutant ALS mice^205,206.
	ESC	Preclinical	Preclinical studies have shown significant rescue of motor impairment and reduced disease progression in response to the grafting of ESC-derived-astrocytes in a rodent model of ALS207.
	ESC	Preclinical	On the basis of preclinical evidence, Phase-I/II clinical trials (NCT03482050 and NCT02943850) are in the pipeline.
Alzheimer’s disease	iPSC	Preclinical	iPSC-derived neural precursors have been reported to improve memory deficits in a mouse Alzheimer’s model²⁰⁸.
Alzheimer’s disease	ESC	Preclinical	Transplantation of embryonic stem cell-derived neural precursors improved cognition and memory in a mouse Alzheimer’s model^209,210.
Huntington’s disease (HD)	iPSC	Preclinical	Mouse iPSC-derived neural precursors improved locomotor deficit in a Huntington’s mouse model²¹¹. This has been recapitulated using patient iPSC-derived neural precursors²¹².
	iPSC	Preclinical	To reduce the risk of pathology development in the graft, iPSC-derived neural precursors, transgenically modified to express reduced levels of the mutant Huntingtin gene, and wild type iPSC-derived neural precursors, showed a significant reversal of motor deficit in a mouse model of HD²¹³.
	ESCs	Preclinical	ESC-derived neural precursors have shown to relieve motor dysfunction and to improve cognitive impairments in a mouse model of HD²¹⁴.