Investigational Herbal Therapy DA-9805 Shows Neuroprotective Effects in Parkinson’s Mouse Model

Investigational Herbal Therapy DA-9805 Shows Neuroprotective Effects in Parkinson’s Mouse Model

An investigational herbal product called DA-9805 exerts its neuroprotective activity by preventing mitochondria damage in brain cells, a mouse study has found.

This compound is currently being evaluated in a Phase 2a clinical trial (NCT03189563) in early Parkinson’s disease patients.

The study, “Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease,” appeared in the journal Scientific Reports.

DA-9805 is an investigational compound being developed by the South Korean company Dong-A ST. It combines natural compounds extracted from three plants widely used in traditional Asian medicine: Moutan cortex, Angelica Dahurica root, and Bupleurum root.

Each of these plants is rich in compounds with broad therapeutic activities, including anti-inflammatory, antioxidant, anti-cancer, and analgesic proprieties.

Supported by their long history of use in traditional medicine for diseases caused by oxidative stress and inflammation, researchers hypothesized that they may also have the potential to treat Parkinson’s disease.

DA-9805 was obtained by extracting the main natural compounds of the three dried plants with 90% ethanol for 24 hours. A detailed analysis of the extracted compounds revealed the mixture was enriched for the active molecules paeonol, saikosaponin A, and imperatorin.

To evaluate the potential of the mixture, researchers exposed a cell line model often used to study Parkinson’s disease to increasing doses of DA-9805 or other reference compounds.

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The treatment significantly prevented cell death induced by impaired activity of mitochondria — small cellular organelles that provide energy and are known as the “powerhouses” of cells — compared with the other tested compounds. The neuroprotective effect of DA-9805 was further confirmed when tested in cells collected from the superficial brain layer of rats.

Next, the team evaluated the effects of oral DA-9805 in a mouse model of Parkinson’s disease. This model was achieved by injecting animals with a neurotoxin called MPTP and its active metabolite MPP+, both of which exert neurotoxic effects on dopaminergic neurons — those that are mainly affected in Parkinson’s disease.

They found that treatment with DA-9805 effectively improved animals’ balance (bradykinesia) compared with placebo-treated mice. This positive effect on balance was similar to that observed in mice treated with approved Parkinson’s therapy Azilect (rasagiline).

Evaluation of dopamine levels in the striatum — the brain area most affected by the disease — showed that DA-9805, similar to Azilect, could also prevent dopamine reduction in the brain associated with Parkinson’s disease in these mice.

Importantly, although both compounds protected striatum dopaminergic neurons from death upon exposure to MPTP, DA-9805 showed a greater neuroprotective effect than Azilect.

These findings “suggest that DA-9805 has neuroprotective effects” in mice with Parkinson’s disease, according to the researchers.

Additional experiments revealed that DA-9805’s therapeutic effects were mediated by enhanced protection of mitochondria and their function, while reducing the levels of damaging oxidative molecules, also known as reactive oxygen species (ROS).

Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals, or ROS, are harmful to the cells and are associated with a number of diseases, including Parkinson’s.

“Given that mitochondria are involved in the pathogenesis of neurodegenerative diseases, we propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics against Parkinson’s disease,” the researchers wrote.

DA-9805 is now being evaluated in a Phase 2a trial in patients with early Parkinson’s disease at the HealthPartners Institute in Minnesota.

Currently recruiting participants, the randomized, double-blind study is expected to enroll about 60 patients between the ages of 30 and 79 who have had mild to moderate Parkinson’s for two years or less.

Participants will be randomly assigned to receive a daily 45 or 90 mg dose of DA-9805, or a placebo for 12 weeks. Researchers will evaluate the safety and tolerability of the treatment, as well as its ability to improve patients’ motor function.

The study is expected to be completed by March 2019.

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