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Global Translational Medicine Parkinson’s: From cause to cure

neurotrophic factor, aromatic L-amino acid decarboxylase, quality of life for patients. However, most gene therapies
and glutamate decarboxylase have shown promising results remain in the clinical trial phase, and their long-term
in PD animal models, though further clinical research is safety and efficacy must be verified through extensive
required to clarify their efficacy and safety. 60 clinical research.
Dopamine transporter deficiency syndrome (DTDS) 3.7. Traditional Chinese medicine treatment
is a progressive and life-threatening neurodegenerative
disease. As children with DTDS age, they exhibit Acupuncture, a major component of traditional Chinese
“Parkinsonian symptoms,” such as bradykinesia and medicine, involves the stimulation of specific acupoints
rigidity, which resemble those seen in PD. Researchers first on the human body through needling or moxibustion to
pointed out that the activity of the dopamine transporter regulate the flow of Qi and blood, as well as the meridians,
(DAT) in DTDS patients is significantly reduced. This low thereby alleviating clinical symptoms and treating diseases.
DAT activity not only leads to reduced expression of key As an important part of the traditional Chinese medical
enzymes involved in dopamine synthesis but also induces treatment system, acupuncture, and moxibustion therapy
apoptosis of midbrain dopaminergic neurons. Introducing have been increasingly applied in clinical practice in
the normal human SLC6A3 gene into the midbrain recent years. A substantial number of clinical studies have
dopaminergic neurons of DTDS patients significantly indicated that acupuncture and moxibustion therapy can
increased DAT activity. Subsequently, researchers alleviate both motor and non-motor symptoms in patients
constructed a recombinant AAV2 vector expressing with PD.
human SLC6A3. When this AAV recombinant virus In addressing emotional disorders such as anxiety
was injected into a mouse model of DAT dysfunction, it and depression, an 8-week acupuncture and moxibustion
was found that DAT expression improved significantly, therapy intervention resulted in a 0.22-point difference
accompanied by enhanced survival rates and reduced in Hamilton Anxiety Scale (HAM-A) scores between the
motor impairments. 59 observation group (PD patients) and the control group.
Recent advancements in gene therapy have enabled Compared to pre-treatment levels, the HAM-A scores in
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the selective regulation of neural circuits affected by PD, the observation group decreased by 7.03 points. Sleep
improving symptoms in PD animal models. D1-MSN and disorders, which are common among some PD patients
D2-MSN are medium spiny neurons in the striatum that and can exacerbate the condition, have also been shown
express dopamine receptor 1 or 2, respectively. D1-MSN to improve with acupuncture. Researchers divided PD
promotes movement, whereas D2-MSN inhibits it, both patients with sleep disorders into a treatment group
receiving signals from the substantia nigra. Researchers receiving real acupuncture (RA) and a control group
modified AAV to construct a novel vector, AAV8R12, receiving sham acupuncture (SA). Parkinson’s disease
incorporating a promoter highly expressed in D1-MSN sleep scale (PDSS) scores were recorded at 4 and 8 weeks
and a chemogenetic manipulation effector. To test this of follow-up. Results indicated that both the RA and SA
vector’s effectiveness and specificity, researchers injected groups showed improvements in PDSS scores compared
AAV8R12-G88P3-HA-hM3Dq, which expresses the to baseline, with increases of 29.65 and 10.47 points,
designed receptor (DREADD) effector hM3Dq activated respectively. Furthermore, the RA group exhibited
by a specifically designed drug, into the substantia nigra significantly greater improvements in PDSS scores than
of mice. Behavioral analysis revealed that activation of the SA group at both 4 and 8 weeks, with increases of 19.75
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D1-MSN in the mouse brain improved motor function. and 20.24 points, respectively.
In addition, the research results suggest that this Acupuncture therapy has also demonstrated certain
gene therapy can regulate signal pathways related to therapeutic effects on the motor symptoms of PD patients.
D1-MSN. Subsequently, researchers used a PD model in After 4 weeks of combined acupuncture therapy and
non-human primates (macaque monkeys) for further traditional PD treatment (traditional treatment refers to
investigation. Using the same AAV8R12 therapy, they the standard medical treatment, which includes levodopa,
observed significant improvements in PD-related motor carbidopa-levodopa, dopamine agonists, anticholinergics,
symptoms of the macaques: tremor symptoms disappeared amantadine, etc.), the acupuncture group exhibited
completely, bradykinesia improved markedly, and motor significant improvements compared to the traditional
abilities showed varying degrees of recovery. Although treatment group. Specifically, gait rhythm was significantly
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there is currently no cure for PD, gene therapy has emerged reduced, whereas stride amplitude, single support
as a promising treatment approach, showing tremendous time, and swing amplitude were significantly increased.
potential in slowing disease progression and improving the Moreover, the UPDRS scores (related to walking and

Volume 3 Issue 4 (2024) 8 doi: 10.36922/gtm.5082