These results indicate that the function of PPT1 has been widely conserved throughout evolution and that S. pombe may serve as a genetically tractable model for the study of human infantile Batten disease.
Based on these findings, and because side effects were not detected, we suggest that clinically approved immune modulators such as fingolimod and teriflunomide may be suitable to attenuate progression of CLN1 and CLN3 disease and, possibly, other orphan diseases with pathogenically relevant neuroinflammation.
Initial work has revealed disturbed metabolic pathways in several NCL disorders and most analyses have utilized the infantile (INCL/CLN1) and juvenile (JNCL/CLN3) disease modeling and utilized mainly human and mouse samples.
Cln3-mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl-protein thioesterases-1 (Ppt1)-protein and Ppt1-enzyme activity in the lysosome.
Using highly informative microsatellite DNA markers in eight multiplex families, we were able to exclude Stargardt's disease from the vicinity of the CLN1 and CLN3 loci.