Chinese Neurosurgical Journal study explores the role of a combined therapy in Parkinson’s disease treatment

Parkinson's disease (PD) is a progressive neurodegenerative condition, affecting the elderly population. The condition results from accumulation of pathogenic proteins and the degeneration of dopamine-producing neurons in the substantia nigra region of the brain. Clinically, PD presents with motor symptoms, such as tremors, bradykinesia, rigidity, and postural instability. It can also involve a variety of non-motor characteristics. Global studies indicate a significant increase in PD cases worldwide, highlighting the need to find suitable treatment approaches to alleviate symptoms associated with PD.

The conventional treatment approach involves levodopa, a dopamine precursor, that helps to alleviate the motor symptoms. However, it is associated with long-term decline in effectiveness, psychiatric side effects, and certain motor complications. While other advanced interventions, involving deep brain stimulation and continuous infusion systems, provide additional options, they are also associated with high cost and adverse side effects. This underlines the need for effective, novel strategies with increased efficacy and safety.

Combination therapies that involve multiple treatments, like two or more drugs or modalities, are often more effective in treating a condition than monotherapies. Some recent studies have focused on using stem cell-based therapies for PD treatment. Brain-derived neurotrophic factors (BDNFs), supporting the growth, survival, and function of neurons, are also considered to be promising therapeutic targets for Parkinson's. A recent review study, led by Dr. Jonny Jonny from Indonesia Defense University, focused on a combination therapy involving these two strategies in PD treatment. “We wanted to explore if combining BDNF with stem cell therapy can promote neuroregeneration and functional recovery in PD,” mentioned Dr. Jonny, while talking about the motivation behind the study. The study was published in volume 11 of the Chinese Neurosurgical Journal on November 06, 2025.

Stem cell transplantation seeks to restore the depleted dopaminergic neurons by introducing progenitor cells. Induced pluripotent stem cells are genetically matched to the donors and hence have reduced risk of immune rejection. However, stem cell therapy has certain limitations, including absence of dependable differentiation systems and the risk of tumor development. “Further optimization can ensure safe and effective use of stem cell therapy in PD treatment,” commented Dr. Jonny.

BDNF upregulation in animal models mitigates neuronal loss and enhances motor function. It interacts with tropomyosin receptor kinase B, a receptor for neurotrophic factors, and activates signaling pathways that suppress apoptosis, enhance synaptic plasticity, and modulate neuroinflammation. However, the inability of BDNF to cross the blood-brain barrier and other systemic or local side effects often hinder its therapeutic delivery.

Researchers are currently investigating a combination of these two therapies to guarantee enhanced efficacy and reduced side effects. In combination approach, stem cells are genetically modified to continuously express and secrete BDNF post-transplantation. Experimental studies show that BDNF-modified stem cells differentiate more effectively into dopaminergic-like neurons. These cells also express transcription factors that improve dopamine secretion. The expression of BDNF enhances neuronal survival by increasing anti-apoptotic protein expression and inhibiting pro-apoptotic molecules. Adverse side-effects like neuroinflammation are also controlled in the combination therapy due to reduced expression of proinflammatory cytokines. Studies in rat models have shown that the combination strategy aided an increase in dopamine level and improvement of behavioral outcomes.

The combination of stem cell transplantation and BDNF enhancement is set to meet both the symptomatic and disease-modifying requirements in PD. Even though certain limitations remain, improvements in cellular engineering, delivery methods, and safety mechanisms could improve adoption of this approach. “If this dual treatment strategy is successfully translated, it can change the way Parkinson's disease is treated. It will help in long-term symptom relief and even change the course of the disease,” concluded Dr. Jonny.

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About Chinese Neurosurgical Journal

Chinese Neurosurgical Journal is an open access, peer-reviewed journal publishing research in all areas of neurosurgery, including new trends in neurology and neuroscience, with a focus on clinical practice and techniques. It is the official journal of the Chinese Neurosurgical Society, which covers the publication costs, so authors do not pay article-processing charges. The journal aims to publish work from neurosurgeons and researchers worldwide. Articles are freely and permanently accessible online immediately after publication, promoting broad dissemination and exchange of neurosurgical knowledge globally. It supports advancements in neurosurgery through high-quality scientific contributions.

Website: https://cnjournal.biomedcentral.com/

About Dr. Jonny Jonny from Indonesia Defense University

Dr. Jonny Jonny is a medical professional affiliated with the Faculty of Military Medicine at the Indonesia Defense University in Bogor, Indonesia. His research spans across nephrology, immunology, and regenerative medicine, demonstrating expertise in complex systemic diseases. In nephrology, he focuses on advanced renal replacement therapies and optimizing peritoneal dialysis, specifically for patients in resource-limited settings. His work in regenerative medicine, which includes autologous dendritic cell vaccines for infectious diseases like COVID-19 and autoimmune conditions, is highly cited. Currently, his team is concentrating on stem cell therapy for Parkinson's disease and other neurodegenerative disorders. He has authored multiple publications in internationally reputed journals.