New treatments may bring new hope to people with Parkinson's disease
Stem cell therapy, immunotherapy, nanomaterial preparations
◎ Tang Fang, reporter of this newspaper
Although Parkinson's disease cannot be completely cured at present, it can be obtained through drugs, surgery, rehabilitation, and psychological counseling. The main treatment of Parkinson's disease is drug treatment, and the 6 types of drugs commonly used at present are levodopa preparations, dopamine receptor agonists, etc. In addition to drugs and surgical treatment, researchers are also exploring some new treatments for Parkinson's disease, such as immunotherapy, stem cell therapy, nanomaterial preparation therapy, etc.
April 4 marks the 11th World Parkinson's Day. Parkinson's disease is a movement disorder that currently affects about 27 million people worldwide.
In China, the average age of Parkinson's disease is 60 years old, and the number of patients has exceeded 300 million. Among them, the incidence rate in the elderly over 65 years old is 1.7%. Parkinson's disease has become a common disease in middle-aged and elderly people after tumors and cardiovascular and cerebrovascular diseases. In addition, young and middle-aged patients with Parkinson's disease have accounted for 5%-10% of the total number of Parkinson's disease patients.
For Parkinson's disease, what is the current status of diagnosis and treatment in China? What are the latest studies? What new therapies are there in the future? The reporter of Science and Technology Daily interviewed relevant experts about this.
There is a "honeymoon phase" in drug treatment
"Dopamine neurons in the substantia nigra region of the brain degenerate significantly in patients with Parkinson's disease." Sun Yongan, chief physician of the Department of Neurology of Peking University First Hospital, introduced to reporters that dopamine neurons participate in sensory perception regulation and human motor coordination. Existing studies believe that Parkinson's disease is caused by damage or degeneration of dopaminergic neurons in the substantia nigra, resulting in decreased dopamine secretion.
The reporter learned that the factors that cause Parkinson's disease include genetics, aging, cerebrovascular disease, brain trauma, etc., and the younger trend of Parkinson's disease patients is also related to environmental toxins, drugs, stress and other factors.
Although Parkinson's disease cannot be completely cured at present, it can be obtained through drugs, surgery, rehabilitation, and psychological counseling.
The main treatment for Parkinson's disease is drug therapy, and 6 classes of drugs are commonly used: levodopa preparations, dopamine receptor agonists, CONT inhibitors, anticholinergics, monoamine oxidase-B inhibitors, and amantadine. "The effect of these drugs is either to supplement dopamine, or to reduce dopamine metabolism, or to increase the efficiency of dopamine utilization." Zhang Liyan, deputy chief physician of the Department of Neurology of Beijing Friendship Hospital of Capital Medical University, said in an interview with reporters before.
However, Parkinson's disease is a neurodegenerative disease, usually the efficacy of the drug is not as good as the initial after 4-5 years of medication, and these four or five years are the "honeymoon period" of Parkinson's disease drug treatment.
Sun Yongan told reporters that normal brain physiological secretion of dopamine is slowly released within 24 hours, while exogenous supplementation of dopamine is "pulse" stimulation, such as levodopa needs to be taken 3-4 times a day. In the early stages of treatment, patients are sensitive to dopamine receptors, and their symptoms do not fluctuate much. However, long-term high-dose dopamine use will reduce receptor sensitivity, resulting in side effects such as short duration of efficacy (end-of-dose phenomenon) and unstable efficacy (switching phenomenon).
For the use of drugs for Parkinson's disease, Sun Yongan said that he advocated following the principle of "not seeking full effect, fine water and long flow", that is, starting from a small amount to relieve symptoms and not affect life.
Parkinson's disease can reach 20-30 years, early patients are recommended to combine drugs with rehabilitation exercises, and some advanced patients can be supplemented with surgery. Compared with nerve nucleus destruction surgery, deep brain stimulation surgery implants a brain pacemaker to achieve nerve regulation by implanting a brain pacemaker in a minimally invasive way, which can achieve the purpose of reducing and controlling symptoms such as tremor and stiffness. This technology has been relatively mature in China and in Europe and the United States.
Innovative research is constantly emerging
Parkinson's disease is easy to be misdiagnosed and missed in the early stage, and the search for markers to improve the diagnostic efficiency of the disease has become a major research hotspot in this field.
In September 2022, a research team from Xiangya Hospital of Central South University discovered a new method of detecting Parkinson's disease through laboratory dogs, confirming that Parkinson's disease patients do indeed have special body odor, which is the world's first report confirming the use of laboratory animals to assist in the diagnosis of human Parkinson's disease. At present, the team is studying its specific mechanism to accelerate clinical translational application.
At the end of November 2022, scientists at ETH Zurich in Switzerland discovered that a group of proteins in the spinal fluid of healthy people and Parkinson's patients have different shapes, and these 11 proteins are expected to be used as novel biomarkers to detect Parkinson's disease. The team plans to thoroughly test and validate the discovered markers, evaluate their efficiency in detecting Parkinson's disease, and more.
In addition to drugs and surgical treatment, researchers are also exploring some new treatments for Parkinson's disease, such as immunotherapy, stem cell therapy, nanomaterial preparation therapy, etc.
"At the moment, immunotherapy is getting more attention." Sun Yongan explained that when abnormal α-synuclein gathers, it destroys the inner workings of brain cells, leading to cognitive impairments caused by brain damage such as Parkinson's disease. Researchers have targeted the disease by preparing vaccines or monoclonal antibodies against α-synuclein. However, at present, the cost of immunotherapy is high, and the off-target rate is high, so it has not achieved a good treatment effect for Parkinson's disease.
Researchers at home and abroad are also trying to treat Parkinson's disease with stem cells. For example, in December 2022, a research team from the Institute of Primate Translational Medicine of Kunming University of Science and Technology developed genetically engineered mesenchymal stem cells that can sustainably and stably secrete dopamine neurotransmitters for the treatment of Parkinson's disease, which can quickly restore motor and non-dyskinesia defects in monkey models of acute and chronic Parkinson's disease.
It is worth noting that nanomaterials are not only good carriers for delivering drugs, some nanomaterials also exhibit neuroprotective effects. In August 2022, the team of Professor Xue Xue of the School of Pharmacy of Nankai University and the relevant team of the Chinese Academy of Sciences used the nanomaterial P-sheet as a drug to inhibit neuronal loss through a certain mechanism and effectively alleviate Parkinson's disease motor dysfunction.
Parkinson's disease diagnosis and treatment need to be more precise
What challenges will Parkinson's disease face in the future?
Experts pointed out that there is still a lack of effective means for early and accurate diagnosis of Parkinson's disease. Early detection and early treatment are beneficial to protect dopamine neurons in the brain and delay the progression of the disease. According to reports, studies have shown that in first-tier cities such as Shanghai, the median time from the onset of Parkinson's disease to diagnosis is 10 months, and the misdiagnosis rate in this process is 23.53%.
In addition, although much progress has been made in the treatment of Parkinson's disease, there are still some difficulties that affect the treatment effect of the disease.
Xue Xue said that for the treatment of brain diseases, the blood-brain barrier is a "hurdle" that cannot be bypassed. The existence of the blood-brain barrier prevents the transfer of most small and large molecules, and the blood-brain barrier crossing rate of existing drugs is less than 5%, which seriously limits the treatment of neurological system diseases.
To solve this problem, on the one hand, we can start by increasing the passage rate of the blood-brain barrier, and on the other hand, we need to enhance the targeting of the drug so that the drug can specifically act on brain cells.
Nanomaterials have broad prospects in increasing the passage rate of the blood-brain barrier and improving specificity. In Xue Xue's team's research, the researchers connected some chaperones or ligands that could target the brain on the polyethylene glycol chain, while increasing the passage rate of the blood-brain barrier by adjusting the size and surface modification of the nanomaterial.
For Parkinson's patients, implanting a neural chip in the brain in the future to work together to combat troubling tremor attacks may be a viable option. In early 2023, researchers at the Swiss Federal Institute of Technology in Lausanne combined low-power chip design, machine learning algorithms and flexible implantable electrodes to create a neural chip that can recognize and suppress the symptoms of multiple neurological diseases, including Parkinson's disease. (Science and Technology Daily)