Neural stem cell therapy in lysosomal storage disorders

Abstract

Many lysosomal storage disorders (LSDs) produce neurodegeneration as a prominent feature (Neufeld, 1991). LSDs are autosomal recessive metabolic diseases caused by deficiencies of specific acid hydrolases resulting in accumulation of unmetabolized substrates and macromolecules in lysosomes. There are ∼50 diseases that can be classified as LSDs. The precise mechanisms underlying the actual neurodegenerative process remain to be determined, however, it is known that replacement of the absent gene product typically restores normal metabolism to a cell including forestalling neural cell dysfunction, at least in vitro. Nevertheless, there are currently no effective treatments for the neurological manifestations of the infantile-onset forms of the LSDs. The neuropathology of LSDs is characterized not by discrete focal neuropathology, as in Parkinson's disease, but rather by extensive, multifocal, or even global neural degeneration or dysfunction. Therapy may require not only therapeutic molecules, such as enzymes, but also widespread neural cell replacement.