In October 2017, Li Jun, an experimenter at Kunming University of Science and Technology, injected a special cell into a rhesus monkey with Parkinson’s disease. Two weeks later, the monkey, already muscular and lying in a cage all day, gradually straightened up and was able to grab food on its own.
This is the most exciting moment that Li Jun has been engaged in scientific research for several years.
They later injected eight more monkeys. Without exception, the monkeys’ original Parkinson’s disease symptoms improved, and over time, the differences from healthy monkeys became smaller. What’s more, after a long 5 years (equivalent to about 22 years of human life), the monkeys still maintained a significant therapeutic effect.
Recently, this paper completed by the team of Professor Li Tianqing and Academician Ji Weizhi of the Institute of Primate Translational Medicine of Kunming University of Science and Technology was published in NPJ Parkinson’s Disease, an important journal in the field of Parkinson’s disease.
First authors: Li Jun (first from left), Li Nan (second from left), Wei Jingkuan (third from left);
Corresponding author: Li Tianqing (first from right)
“Plant” cells in the brain that can cure disease
Parkinson’s disease is the “third killer” of middle-aged and elderly health after tumors, cardiovascular and cerebrovascular diseases, and its morbidity and mortality are very high, with a mortality rate of 66% within 6 years.
Parkinson’s disease is caused by the death of dopaminergic neurons in the substantia nigra of the midbrain, resulting in decreased dopamine secretion in the striatum. Therefore, the current clinical drug treatment methods are mainly oral L-L-dopamine. But almost 99 percent of the substance is metabolized in the blood system, and only about 1 percent enters the brain to function. Such drugs not only have low utilization, but also easily lead to a series of side effects such as movement disorders, cognitive impairment, sleep disorders, etc.
The Li Tianqing/Ji Weizhi team has long been committed to primate stem cell research. They wondered if they could make a genetically engineered cell and transplant it into the striatum so that it could express the dopamine neurotransmitter directly in the brain. If such cells can survive in the body, they can continuously release the dopamine neurotransmitter. This is more convenient than taking medicine regularly, and in the long run, the cost is lower.
“The idea was originally born in 2014.” Li Tianqing told China Science News that he happened to undertake a project of the Ministry of Science and Technology on Parkinson’s stem cell therapy. His team transferred three specific genes: TH, GCH and AADC into a cell line that could express the dopamine neurotransmitter. After extensive safety assessments, they first injected the genetically engineered mesenchymal stem cells into rats with Parkinson’s disease. After a week or two, the rats experienced significant relief in their symptoms.
“We were so uplifted by this phenomenon that I almost didn’t fall asleep at all for two nights.” Li Tianqing said, “We immediately decided to carry out primate experiments on this basis. ”
If this therapy can also be safely effective in primates closest to humans, it would undoubtedly be a major breakthrough.
At the same time, everyone knows what a long research cycle does doing primate experiments mean.
When you see hope, hold on a little more
Li Jun took over this topic when he was a master’s student. At that time, a senior brother and sister reminded him: this project cycle is too long, it may affect graduation, it is better to do something else.
But Li Jun’s thoughts are different. His grandfather suffered from severe Parkinson’s disease, and in just a few years, his life deteriorated step by step from being able to go out for a walk every morning to trembling involuntarily, and his life gradually became difficult to take care of himself. Because of this, he has a different kind of affection for this subject.
“Especially when the cells were injected into rats and monkeys, and seeing that these animals had improved significantly, I thought, since I see hope, why not hold on more?” He said.
The research process was challenging. They started with the construction of a model of rhesus macaques with Parkinson’s disease. Initially, the monkeys developed symptoms similar to Parkinson’s disease, and everyone thought that the model was successful. But after talking to the clinician, I found that the monkey’s symptoms were not so typical.
In order to have a deeper understanding of this disease, Li Jun and others also joined the group of patients with Parkinson’s disease, and consulted their personal experiences like doing interviews. They also exchanged views with researchers in related fields, summarized the experience of all parties, and finally successfully established the first stable Parkinson’s disease model monkey on December 12, 2016.
With the successful modeling work, Li Jun did not suffer a delay as many expected, and successfully obtained a master’s diploma. After graduation, he did not continue his doctoral studies, but according to his characteristics and strengths, he stayed here as an experimenter and continued to deal with monkeys.
After 2017, he saw firsthand the monkeys who had received genetically engineered mesenchymal stem cell injections begin to resume exercise, regain food intake, and gradually return to levels close to those before the disease. The monkeys in the control group were in a deteriorating condition.
Initially, they intended to observe for only two years. However, two years passed, and the monkeys were getting better and better, during which time there were no special treatments other than two mesenchymal stem cell transplants. This surprised and surprised the researchers, so they decided to continue the observation, which was a full 5 years.
Monkeys in all treatment groups, including those with severe disease who had completely lost their ability to move and eat at one point, maintained good treatment results over the 5 years.
Group photo of the team
When will it go clinical?
In August 2022, the research team submitted this work to NPJ Parkinson’s Disease, a well-known journal in the field of Parkinson’s disease, and the review process was very smooth, and the paper was published online on December 22, 2022.
“Your research article reports interesting results… The results convincingly support the conclusion that after transplantation of dopamine-mesenchymal stem cells, the animals showed improved motor behavior and cognitive recovery related to striatal dopamine levels. This paper makes an important contribution to the field of cell replacement therapy for Parkinson’s disease. The reviewer wrote.
After the paper was published, Li Tianqing received a lot of messages from Parkinson’s disease patients. They asked: When will you be able to put this into practice?
“From the current animal tests, our therapy has the advantages of simple operation, quick effect, and stable maintenance of efficacy for a long time. Especially compared with other cell drugs, such as CAR-T anti-cancer drugs that cost 1.2 million yuan per injection, this engineered cell is easy to expand, so the treatment cost will not be very high. Li Tianqing said.
They are currently working with companies to standardize, scale the preparation of such cells, and after a lot of safety and efficacy evaluation, further advance to clinical trials.
“I’m just a researcher, and I’m not very good at follow-up clinical trials and commercial collaborations. Therefore, I hope that professionals in related fields can participate and work with us to promote it. Li Tianqing said, “If this achievement can be truly applied to the clinic in the future and benefit the majority of Parkinson’s disease patients, it will be our most honored thing.” (Source: Li Chenyang, China Science News)
Related paper information:https://doi.org/10.1038/s41531-022-00440-6
(All photos in this article are provided by Li Tianqing Lab)