Exported Molecules that Distinguish Normal and JNCL Fibroblasts as a Biomarker for JNCL Disease Progression and Therapeutic Efficacy

Neuronal ceriod lipofuscinoses (NCL) is an autosomal recessive neurological disease characterized by four main types of onset, which have all become more commonly referred to as Batten’s disease. The forms of NCLs are grouped by age, the most common has a strong fatal tendency, especially in the juvenile age group. Areas of physical impairment are vision and motor ability as patients develop blindness, seizures, and ataxia, resulting in death. The neurological symptoms may appear as indistinguishable from other neurological diseases resulting in a devastatingly late diagnosis. The major cause of JNCL is a 16p.12.1 CLN3 deletion, with an unclear CLN3 protein function.  What is known is that the CLN3 protein affects the storage of specific endosomal cargo, associated to both endosomal and lysosomal pathways. Studying the complexes exported by the cell can indicate this abnormality. Speculation of other protein accumulation leads us to investigate exosomal composition as a target to find differences between normal and JNCL patient fibroblasts. Fibroblasts were probed with various antibodies and results indicated no significant difference in exosomal release, however, the CLN3 deletion appears to reduce the export of some, but increase the export of other proteins from the fibs that are clearly identifiable by silver-staining.