Jonathan A. Fidler

TL;DR: It is shown that adeno-associated virus serotype 4 (AAV4)-mediated expression of insulin-like growth factor-1 (IGF-1) or vascular endothelial growth factor (VEGF)-165 in the cellular components of the ventricular system leads to trophic factor delivery throughout the CNS, delayed motor decline and a significant extension of survival in SOD1(G93A) transgenic mice.

TL;DR: Intensive investigation of the major determinants of H+ concentration suggests that acidosis is also due in part to the presence of an unknown anion, which provides insights into the pathogenesis of ALS as well as potential targets for drug development.

TL;DR: Animals treated by combination therapy exhibited high levels of hASM in the viscera and brain, which resulted in near-complete correction of storage throughout the body, resulting in normal weight gain and superior recovery of motor and cognitive functions compared to animals treated by either brain or systemic injection alone.

TL;DR: The extensive neuropathologic alterations in this model suggest that therapy of skeletal and cardiac muscle disorders by systemic enzyme replacement therapy may not be sufficient to reverse functional deficits due to CNS glycogen storage, particularly early-onset, rapidly progressive disease.

TL;DR: The effectiveness of intracerebroventricular delivery of recombinant human ASM into ASMKO mice showed that ICV delivery of the enzyme led to widespread distribution of the hydrolase throughout the CNS and a significant reduction in lysosomal accumulation of sphingomyelin was observed throughout the brain and also within the spinal cord and viscera.