Parkinson's disease is a common neurodegenerative disorder among the elderly, characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies, along with decreased dopamine neurotransmission in the striatum. Clinically, it is distinguished by motor symptoms such as resting tremor, muscle rigidity, bradykinesia, and postural instability, as well as non-motor symptoms including sleep disturbances, olfactory dysfunction, autonomic dysfunction, cognitive impairments, and psychiatric disorders.
As the disease advances, both motor and non-motor symptoms of Parkinson's disease worsen gradually, posing significant challenges to patients' health and imposing substantial societal burdens. In the field of Parkinson's disease research, relentless efforts have been made, particularly yielding numerous significant advancements in 2023.
Research Breakthrough in Understanding Parkinson's Disease Mechanisms
Significant progress has been made in understanding the pathogenesis of Parkinson's disease through studies focusing on genetics and cellular mechanisms. Researchers from the Feinberg School of Medicine at Northwestern University in the United States have discovered that mutations in the Parkin gene can lead to familial Parkinson's disease. Normal neuronal activity requires a large amount of energy, which is highly dependent on mitochondrial function. During mitochondrial activity, a large number of cellular fragments are generated, which need to be cleared by lysosomes. Researchers have found that mutations in the Parkin gene can disrupt the connection between these two key components (lysosomes and mitochondria) in human cells, leading to neuronal apoptosis due to the accumulation of cellular fragments. It has also been confirmed that individuals with mutations in both copies of either PINK1 or Parkin are susceptible to Parkinson's disease due to the dysfunction of mitochondrial autophagy.
A genome-wide association study (GWAS) conducted on African Parkinson's disease patients revealed a new genetic risk factor, GBA1, which has not been found in European populations. This study suggests that some African American patients may carry the pathogenic gene GBA1, thus participating in the pathogenesis of Parkinson's disease in this population. The findings were published in Lancet Neurology.
Researchers also investigated the effects of iron chelation therapy on the progression of Parkinson's disease, with the study published in the New England Journal of Medicine. They designed a randomized controlled trial involving newly diagnosed Parkinson's disease patients who had not received levodopa therapy. The results showed that iron chelation therapy did not delay the progression of Parkinson's disease and may even worsen the condition in patients. Further research is needed to elucidate the role of iron deposition in the pathogenesis of Parkinson's disease.
Emotional and microplastic exposure risks identified, early detection possible with smart devices
A study led by Terracciano A utilized data from the UK Biobank, involving 491,603 samples. The results indicated that individuals reporting feelings of loneliness had a 37% higher risk of developing Parkinson's disease compared to those who did not report loneliness. This association remained consistent across different risk assessment models, suggesting a close link between emotional and mental health and Parkinson's disease. The study was published in JAMA Neurology.
A study from Duke University's Center for Neurodegeneration and Neurotherapeutics proposed a new perspective on the potential association between microplastic exposure and Parkinson's disease risk. In this study, researchers first mixed high concentrations of α-synuclein monomers with anionic polystyrene nanoparticles and observed changes in α-synuclein aggregation. The results showed a high affinity between anionic polystyrene nanoparticles and human α-synuclein, promoting α-synuclein aggregation. Mouse models also demonstrated potential neurological effects.
Schalkamp AK and colleagues utilized data from the UK Biobank, involving 103,712 individuals aged 40 to 69, who wore medical-grade smartwatches to measure daily activity acceleration. They compared this data with another group of diagnosed Parkinson's disease patients. The results showed that wearable devices (smartwatches) could identify Parkinson's disease up to 7 years before the onset of characteristic symptoms, indicating that passive collection of motion tracking data could serve as an early indicator for predicting the future development of Parkinson's disease. The relatively low cost of this technology makes it feasible for large-scale non-invasive screening of populations in the future.
Effective improvement in prognosis with FUS-A, gene therapy, and others
In February 2023, a study from the University of Virginia led by W. Jeff Elias focused on Parkinson's disease treatment. Through a randomized controlled study, a group of patients underwent focused ultrasound ablation (FUSA) treatment on the subthalamic nucleus, while the control group received sham surgery. Follow-up assessments using the MDS-Unified Parkinson's Disease Rating Scale comprehensively evaluated the patients. The results showed a higher proportion of patients with improved motor function in the unilateral FUSA group compared to the sham surgery group. This study holds promise for providing valuable means of treatment for Parkinson's disease patients.
Researchers also explored the use of neural implant devices, demonstrating that epidural electrical stimulation (EES) of the lumbosacral dorsal roots could significantly alleviate motor impairments caused by Parkinson's disease. In one trial, a 62-year-old patient with a 30-year history of Parkinson's disease who had previously undergone deep brain stimulation (DBS) therapy and dopamine replacement therapy with poor results and experienced severe daily falls. After two years of using the device, the patient can now walk several kilometers outdoors independently. These findings were published in Nature Medicine.
Cell replacement therapy, as a novel treatment for Parkinson's disease, has significant therapeutic potential but also limitations, as researchers found that transplanted dopamine-producing neurons survive very poorly. Scholars from Harvard University published their latest research in Nature, demonstrating that co-transplantation of regulatory T cells (Tregs) and midbrain dopamine progenitor cells (mDAP) into rodent models' brains reduced adverse reactions following cell therapy. While this conclusion is limited to animal models, it provides a new direction for cell transplantation therapy.
In 2023, significant progress was also made in gene therapy for Parkinson's disease in China. Researchers from the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences developed a new AAV capsid-AAV8R12 (which efficiently retrogradely labels striatal D1-MSNs) and a novel promoter-G88P2/3/7 (which drives target genes to be widely expressed in striatal D1-MSNs) for gene therapy. The research team also screened chemical genetic elements rM3Ds, which matched systemic administration, to specifically activate D1-MSNs, thereby driving the direct pathway mediated by D1-MSNs. Compared to levodopa, this therapy not only significantly improves efficacy but also acts more quickly and has a longer duration of action. The aforementioned research undoubtedly significantly advances the field of Parkinson's disease. Looking ahead, we anticipate making further groundbreaking progress in Parkinson's disease research. At the same time, we hope that society as a whole can pay more attention to Parkinson's disease and work together to improve the well-being of patients.
(Affiliation: Tongji Hospital, Tongji University)
