Parkinson's disease.
It is the most common degenerative brain disease after dementia. If dementia has symptoms of memory loss, Parkinson's disease is a loss of motor ability. In fact, Parkinson's disease causes symptoms such as tremors, muscle stiffness, and unstable posture.
Parkinson's disease is reported to occur in about 1 to 2 cases per 1000 population, but because it is a degenerative disease, it mainly occurs in the elderly, so if the statistical range is limited to the elderly, the frequency is very high.
Since the known cause is the loss of nerve cells that produce dopamine, artificially injecting dopamine for treatment is widely used. A well-known drug is Levodopa. In the early stages of treatment, the effect of the drug is very good and they can lead a normal daily life. However, side effects appears as time passes after using the drug (3 years~).
The research paper that I will introduced today is a method of treatment with a fundamentally different mechanism from the levodopa, approaching the causes of Parkinson's disease in a preventive way and present the results of clinical studies.
For reference, brain cells continuously clean waste products from the cells through lysosomes. Therefore, impairment of lysosome functions result to dementia and Parkinson's disease by accumulation of cellular waste.
Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease
Paper summary
"Mutation of the LRRK2 protein is a high risk factor for Parkinson's disease. LRRK2 mutation leads to overexpression, resulting in suppression of lysosome function. So, inhibiting LRRK2 would be a good way to treat Parkinson's disease.
DNL201(which is a small molecule) not only has the ability to inhibit LRRK2, but also able to penetration of the BBB (Blood-brain barrier).Through preclinical experiments, they confirmed that DNL201 inhibited the activity of LRRK2, and it was also reported that lysosomes again showed normal activity in brain cells of mice and patients.In a clinical trial, the performance of DNL201 was tested in 122 healthy volunteers and 28 volunteers with Parkinson's disease, and it was confirmed that the drug delivered well into the brain with no side effects."
Let's look at the results of the experiment in cells.
In the graph above, please focus on the graph which marked in orange color.
LRRK2 G2019S is a mutation form of LRRK2, which shows that lysosomal degradation is increased by DNL201 treatment. (It means that the waste products in the cells are being cleaned well.)
Researchers additionally conducted experiments on cells, mice and primates to show that they were non-toxic and that lysosome activity was revived.
Finally, clinical trials were conducted on healthy volunteers and Parkinson's disease volunteers.
Let's look at the effect of the drug graphically.
Patients with Parkinson's disease have high levels of BMP in their urine. The reason is that BMP has to be degraded by lysosome, but the function of lysosome is suppressed by LRRK2 and high level of BMP was detected in urine.
The concentration of BMP in the urine decreased as the concentration of DNL201 was increased (left graph). In addition, it was confirmed that this drug continued for a month and keeping the concentration of low level of BMP in the urine.
Conclusion
In the past, we didn't know how Parkinson's disease occurred, so we didn't know how to treat it.
However, with the efforts of numerous researchers and the cause of Parkinson's disease was discovered. Therefore, treatment strategies were devised and many treatments are now emerging.
With the development of science and medical technology, the lifespan of human beings has been greatly extended. But I think it's more important to stay healthy and not get sick while you're alive, rather than simply living a long life. So, I hoped that sooner or later it will be commercialized for patients with Parkinson's disease and their families.
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