Studying the role of Insulin Degrading Enzyme (IDE) in Parkinson`s Disease using IDE-specific antibodies

Parkinson`s disease (PD) is the second most common chronic progressive neurodegenerative disorder which predominately leads to the death of dopaminergic neurons, affecting the central nervous system, particularly the motor system. The cause of cell death is poorly understood but involves the accumulation of cytoplasmic inclusions termed Lewy bodies, involving Alpha-synuclein as the major component. Today, there is no cure for PD and current treatments may only relieve symptoms.

Insulin Degrading Enzyme (IDE) is a zinc metalloprotease with high affinity to insulin that particularly abundant in the brain, liver, kidney and muscles. IDE has been suggested to be involved in pathogenesis of diverse pathological conditions, including PD, as insulin found to reduce α-synuclein accumulation. Inhibition of IDE activity was suggested as a therapeutic approach for diabetes since the early 1950`s, however, very few specific inhibitors for IDE are available today.

This study aims to establish a novel approach for the treatment of PD, using the inhibitor anti-IDE antibody H3 which was discovered, designed, and produced in our Lab. We found that serum IDE levels are higher in some PD patients, suggesting its involvement in diseases progression. We could identify a positive correlation between serum IDE levels and non-motor symptoms scale (NMSS). Additionally, anti-IDE H3 antibody was found to reduce stress in stress-induced HepG2 cells, and α-synuclein aggregation in the mice substantia nigra, in-vivo. Our findings suggesting that anti-IDE H3 antibody is highly specific to IDE and treatment might alleviate the severity of disease and may be a potential treatment for PD.