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Treatment of Parkinson’s Disease Using Corynoxine B
Neurodegeneration is featured by abnormal protein aggregations in the central nervous system. Parkinson’s Disease (PD) is the second most common neurodegenerative disease that is characterized by the formation of alpha-synuclein (α-Syn) positive aggregates in the dopaminergic neurons. PD affects 1.5% of the global population over 65 years of age. In China, there are two million PD patients, accounting for 40% of PD cases worldwide. Global data analysis showed that in 2011, the global PD therapeutics market including key markets, US, Japan, Germany, UK, France, Italy, Spain, Brazil, China, India and Russia, was estimated to worth $2,992 million. The market size was primarily driven by two key parameters: rising PD prevalence due to the increase in the aging population in these key markets, and the increasing costs of therapy. The global PD therapeutics market is expected to grow at a Compound Annual Growth Rate (CAGR) of 12.6% and is forecasted to reach $11.5 billion by 2029.
Macroautophagy (autophagy) plays an important role in maintaining proper neuronal function by removing damaged or abnormally modified proteins (including toxic protein aggregates) in neurons. Targeting the autophagic pathway for the degradation of pathogenic protein aggregates has emerged as a novel and promising strategy for the treatment of PD.
The present invention introduces an autophagy enhancement compound, Corynoxine B (Cory B). Cory B can enhance autophagy by promoting the degradation of α-Syn in a Beclin-dependent manner. This can prevent the accumulation of toxic protein aggregates in treating neurodegenerative diseases such as PD and Alzheimer's disease.
Technology Features, Specifications and Advantages
The present technology presents a synthetic compound inspired by natural herbs, which includes Corynoxine B (Cory B) analogues and tetracyclic oxindole alkaloids that induce autophagy in neurons to degrade protein aggregates both in vivo and in vitro.
This synthetic compound is based from a natural herb Gou teng and has been used by Chinese doctors for over 2000 years to treat “the shakes” – now known as Parkinson’s disease (PD). In a 2011 double-blinded study, 115 people with PD were given a combination of traditional Chinese medical herbs, including gou teng, or a placebo for 13 weeks. At the end of the study, volunteers who had taken the herbs slept better, and had more fluent speech than those taking the placebo.
The current technology can be developed as bioactive supplements to alleviate the conditions of Parkinson’s Diseases (PD). This can also be further developed into a drug candidate for PD.
As a synthetic analogue of the active of the natural compound of Corynoxine B (Cory B), the technology presents a pure and more potent form of its natural active ingredient found in Gou teng. Thus, this synthetic analogue can be easily manufactured at scale and produced as medical grade or food grade compounds.
Parkinson’s disease symptoms, such as muscle tremors, slowness of movement and rigidity, are caused by the progressive destruction of brain cells that produce dopamine. Previous work has suggested that an accumulation α-Syn aggregates may be causative for such neuronal damage. Current treatments aim to boost the levels of dopamine, which only partly alleviates disease symptoms and does not affect the protein clusters.
It is thought that clumps of α-Syn accumulate because the brain cells cannot remove them through autophagy – a type of programmed cell death. This has been demonstrated in mice without the genes needed for autophagy where these animals quickly developed Parkinson’s-like symptoms.
The current technology presents a possible solution to this by enhancing autophagy through promoting the degradation of α-Syn in a Beclin-Dependent manner. Being found as an active compound in Gou teng, Corynoxine B (Cory B) has shown its efficacy in treating the conditions of PD. The technology aims to deliver such potential benefits to the PD patients.