Neurodegenerative Disorders



 

Plex has programs to develop modulators of heat shock proteins (Hsp) and FK506 Binding Protein (FKBP) as treatments for proteopathic neurodegenerative diseases (PNDDs) such as Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease.

PNDDs comprise a group of CNS diseases characterized by intra and extracellular deposition in neurons and other CNS cells of misfolded protein oligomers, aggregates, fibrils and plaques, all of which ultimately contribute to disease pathology. Some of the most common PNDDs in order of frequency include Alzheimer’s disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).

One therapeutic strategy aimed at removing or preventing accumulation of misfolded proteins in PNDDs is to target components of the protein homeostasis network (PHN) that include Hsps. The PHN functions both in promoting proper protein folding and in disposal of improperly folded proteins.

Hsps, many of which can readily be stress-induced, are intimately involved as protein chaperones by participating in many stages of protein folding and degradation. Plex’s goal is to take advantage of these properties of Hsps as a targeted approach to treat ALS, PD and other PNDDs.

FKBPs consist of a family of related proteins that normally have many important cellular functions, but in Parkinson’s disease (PD) certain FKBPs play a pathological role by promoting aberrant protein aggregation. Plex’s goal is to discover small molecule FKBP inhibitors as a treatment for PD.