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Global Translational Medicine Parkinson’s: From cause to cure

method that has garnered increasing attention in clinical units. They were followed for 12 months, with assessments
settings. It is currently used in the clinical treatment of conducted using the MDS-UPDRS score. Results indicated
diseases across 11 major human systems. Stem cell therapy that from the 3 month of follow-up, MDS-UPDRS scores
rd
offers a novel treatment approach, with its core concept continued to improve compared to baseline, with the most
centered on replacing lost dopaminergic neurons through significant improvement observed at 6 months, averaging
stem cell transplantation to rebuild neural function. Stem a decrease of 19.9 points across the three treatment groups.
cells, characterized by self-renewal and multi-lineage Notably, the degree of clinical symptom improvement was
differentiation, primarily include mesenchymal stem cells not correlated with the transplant dose. 55
(MSCs), embryonic stem cells (ESCs), neural stem cells Finally, iPSCs, with the potential to differentiate into
(NSCs), and induced pluripotent stem cells (iPSCs). 51 cells or tissues of all three germ layers, are increasingly
First, MSCs, which belong to adult stem cells, are being applied in clinical applications. Researchers induced
currently the most widely used in clinical practice. In human iPSCs into midbrain organoids (hMOs) resembling
one study, researchers recruited 23 PD patients, with fetal ventral mesencephalon tissue and transplanted them
12 patients in the experimental group receiving MSC into a PD mouse model. Observations conducted over
transplantation and 11 patients in the control group 12 weeks following transplantation revealed surviving A9
undergoing drug therapy without placebo injection. The midbrain dopaminergic neurons in the striatum. The study
researchers assessed motor and non-motor symptoms indicated that the axons of hMO-derived neurons extended
using the MDS-UPDRS score (Section III), the Hamilton and integrated into the mature central nervous system,
Depression Scale, the Pittsburgh Sleep Quality Index, the thereby alleviating motor dysfunction in PD mice. 56
Epworth Sleepiness Scale, the Non-Motor Symptoms Scale, Stem cell therapy for PD represents a cutting-edge field
and the 39-Item PD Questionnaire. Assessments were of medical research with positive results from laboratory
conducted before transplantation and 1 and 3 months after studies and preliminary clinical trials. However, further
transplantation. The results indicated that motor and non- clinical data are needed to verify its long-term efficacy and
motor symptoms in the experimental group significantly safety.
improved compared to the control group after MSC
transplantation. A meta-analysis of the clinical effects of 3.6. Gene therapy
52
MSC treatment for PD revealed that MSCs could improve Gene therapy involves introducing normal or therapeutic
motor and memory function in pre-clinical PD models and exogenous genes into target cells through specific
offered certain protective effects on dopaminergic neuronal mechanisms, influencing their gene expression and thereby
function. The study further noted that transplanting MSCs altering the biological characteristics of the target cells
containing neurotrophic factors into the brain’s striatum to achieve therapeutic purposes. Gene therapy, with its
had the strongest impact on improving motor function precision, safety, and effectiveness, is gradually transitioning
and protecting dopaminergic neuronal function. 53
from laboratory research to clinical applications. As
Second, ESCs, isolated from early embryos, can research on PD advances, the role of genetic abnormalities
differentiate into mature dopaminergic neurons. in PD pathogenesis is becoming increasingly evident.
Researchers induced the differentiation of human ESCs High-penetrance genes associated with PD include SNCA,
into midbrain dopaminergic neurons, named TED-A9. VPS35, PINK1, PARK7, and PLA2G6; variable-penetrance
After transplanting midbrain dopaminergic neurons into genes include LRRK2 and GBA; and genes related to PD
the right brain of a rat PD model, measurements taken but potentially unrelated to pathogenicity include HTRA2,
16 weeks later showed a significant improvement in UCHL1, GIGYF2, and EIF4G1. 57,58
dopamine secretion in the experimental group compared At present, adeno-associated virus (AAV)-based gene
to the control group. At 11 months post-transplantation, therapy has shown tremendous potential in the treatment
DNA content analysis confirmed the presence of human of central nervous system diseases. A review highlighted
cells in the rat brain without affecting survival rates or that clinical studies suggest AAV gene therapy has certain
causing tumor formation. 54 therapeutic effects on neurodegenerative diseases such

Third, NSCs, capable of differentiating into neurons, as PD and Alzheimer’s disease, neuromuscular diseases
oligodendrocytes, and astrocytes, have been explored in PD such as spinal muscular atrophy and amyotrophic
treatment. In one study, researchers transplanted human lateral sclerosis, and lysosomal storage diseases such
NSCs (ANGE-S003) into PD patients through the nasal as mucopolysaccharidosis and Pompe disease. In
59
mucosa. Patients were divided into three groups based addition, gene therapies targeting the expression of glial
on transplant doses: 1.5 million, 5 million, and 15 million cell line-derived neurotrophic factor, cerebral dopamine

Volume 3 Issue 4 (2024) 7 doi: 10.36922/gtm.5082