A BBB-Crossing Protein Savior For Damaged Neurons

Parkinson’s disease (PD) isa neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons, leading to clinical symptoms such as exercise relaxation, tremor, and postural instability. The pathological hallmark of PD is the abnormal accumulation of α-synuclein, resulting in the formation of Lewy body in the dopaminergic neurons. These striking clinical features have focused efforts to understand the mechanisms responsible for neuronal death and reasons why dopaminergic neurons are differentially affected. In these neurogenerative microenvironment, Parkin protein, which functions as an E3 ubiquitin ligase, appears to rescue dying neurons from toxic and abnormal accumulations of cellular components despite the complexity of PD etiology.

iCP-Parkin as a superior disease-modifying anti-PD agent

An improved cell-permeable Parkin (iCP-Parkin) is our first-in-class Parkinson’s Disease (PD) drug candidate, which can penetrate the Blood Brain Barrier (BBB) and recover the damaged dopaminergic (DA) neurons. It is a Therapeuticmolecule Systemic Delivery Technology (TSDT) applied Cell-/Tissue-permeable Parkin recombinant protein. Like endogenous Parkin, iCP-Parkin can have cytoprotective action by recovering dysfunctional mitochondria through mitophagy and mitochondrial biogenesis. iCP-Parkin can reduce the accumulation of pathological α-Synuclein, thereby suppressing PD phenotypes. Currently, typical PD treatment such as L-Dopa employs symptom-relieving drugs replenishing the loss of Dopamine in brain, temporarily recovering patient’s abnormal motor function. Although the symptom maybe eased, it is not addressing

Therefore, the disease will get worse as time passes and side effects will be occurred. In contrast, iCP-Parkin has neuroprotection capability against PD-induced cellular stress, having a great potential as a disease-modifying therapy for PD biotherapeutics.

In AAV-α-Synuclein-induced PD mouse models, conducted in Severance Hospital and Cellivery, the behavior deficit was recovered with the treatment of iCP-Parkin, and the accumulation of pathological α-Synuclein was removed in the SN, with the recovery of tyrosine hydroxylase (TH) level.

Currently, in collaboration with Ildong Pharmaceutical CO., LTD, we are conducting preclinical R&D of iCP-Parkin at various global GROs and CMOs to move forward more rapidly to clinical development process.Also, Cellivery as a first-time grant recipient in South Korea, established iCP-Parkin research in support of Michael J. Fox Foundation (MJFF) for Parkinson’s Research (MJFF Program: No.14241. 2017. 07 ~ 2019. 03).