CNS Therapeutics That Target Neuronal Ceroid-Lipofuscinoses and Thioesterase Deficiency Disorders

Clinically known as Neuronal Ceroid-Lipofuscinoses (NCL), Batten disease, is a rare neuron killing disease and one of the lysosomal storage disorders (LSDs).  It is associated with a mutation or lack of palmitoyl-protein thioesterase-1 (PPT1) gene. It manifests very early in a child's life causing absence of brain activity as early as 4 years of age.

Dr. Mukherje of NICHD has discovered and developed N-t-BuHA, a chemical derivative of hydroxylamine that mimics the action of PPT1 enzyme.  Compared to hydroxylamine, N-t-BuHA has been shown to be non-toxic in mice expressing batten disease.  In addition, NtBuHA exhibited potent antioxidant property and extended the life of the diseased mice. NtBuHA has shown promising therapeutic potential to treat NCL-LSDs.