DIETARY CARNITINE SUPPLEMENTS SLOW DISEASE PROGRESSION IN A PUTATIVE MOUSE MODEL FOR HEREDITARY CEROID-LIPOFUSCINOSIS

The childhood ceroid-lipofuscinoses are a group of autosomal recessive ly inherited disorders characterized by massive accumulation of autofl uorescent lysosomal storage bodies in neurons as well as other cell ty pes, The storage body accumulation is accompanied by severe degenerati on of the central nervous system that results in blindness, cognitive and psychomotor degeneration, and premature death, On the basis of pat hologic and biochemical criteria, a hereditary disease in the mnd mous e strain has been proposed as a model for certain types of human ceroi d-lipofuscinosis, Experimental evidence suggests that the storage body accumulation in humans with juvenile and late-infantile ceroid-lipofu scinosis is linked to altered carnitine biosynthesis. On the basis of the latter observation, a study was performed to determine whether die tary carnitine supplements could slow the disease progression in the m nd mouse model, Carnitine supplementation begun at 4 weeks of age did not slow the retinal degeneration that is characteristic of this disea se. It did, however, significantly elevate brain carnitine levels, slo w the accumulation of autofluorescent storage bodies in brain neurons, and prolong the lifespans of the treated animals, These findings sugg est that there is a link between carnitine biosynthesis and the diseas e pathology and indicate that carnitine supplementation may be benefic ial in slowing the disease progression in humans with certain types of hereditary ceroid-lipofuscinosis. (C) 1997 Wiley-Liss, Inc.