Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disease
caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1).
Ppt1 knockout mice display hallmarks of INCL and mimic the human pathology: accumulation
of lipofuscin, degeneration of CNS neurons, and a shortened life span. Purified non-genetically
modified human CNS stem cells, grown as neurospheres (hCNS-SCns), were transplanted
into the brains of immunodeficient Ppt1(-/)(-) mice where they engrafted robustly,
migrated extensively, and produced sufficient levels of PPT1 to alter host neuropathology.
Grafted mice displayed reduced autofluorescent lipofuscin, significant neuroprotection
of host hippocampal and cortical neurons, and delayed loss of motor coordination.
Early intervention with cellular transplants of hCNS-SCns into the brains of INCL
patients may supply a continuous and long-lasting source of the missing PPT1 and provide
some therapeutic benefit through protection of endogenous neurons. These data provide
the experimental basis for human clinical trials with these banked hCNS-SCns.