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Global Translational Medicine Parkinson’s: From cause to cure

3.3. New drug development as memory, executive function, language, and mood.

New drug development in PD pharmacotherapy remains Results indicated that post-DBS, PD patients experienced
a major area of research focus. α-Syn, a protein encoded slight improvements in anxiety and depressive symptoms
by the SNCA gene and composed of 140 amino acids, compared to pre-operative levels; however, declines were
plays a role in cellular DNA repair. However, under observed in long-term memory, language fluency, and task-
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pathological conditions, its abnormal aggregation forms specific performance. The study also pointed out that these
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Lewy bodies, showing certain neuronal toxicity. Therefore, cognitive impacts may improve over time. While DBS
α-syn misfolding inhibitors have demonstrated promising significantly improves motor symptoms in PD patients, its
results in clinical trials for PD treatment. In addition, long-term effects on certain cognitive functions warrant
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research has highlighted the neuroprotective potential of further research to balance its therapeutic effects and
glucagon-like peptide 1 receptor agonists, c-Abl inhibitors, cognitive side effects.
and ceftriaxone in animal models of PD with dementia. 2.4.2. Focused ultrasound ablation (FUSA)
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As our understanding of the pathogenesis of PD
advances, the development of more targeted drugs in PD FUSA is a non-invasive treatment that uses focused
pharmacotherapy is anticipated, offering improvements in ultrasound waves to disrupt specific brain areas. In a
long-term prognosis and quality of life for patients. randomized controlled trial, 94 PD patients were divided
into two groups: the experimental group received FUSA
3.4. Surgical treatment treatment (69 patients), whereas the control group
underwent sham surgery (25 patients). All patients
With advancements in medical technology, surgical
treatment has become increasingly important in managing exhibited motor disabilities during the “off” period (off-
PD. Initially, surgical interventions primarily focused on medication state, defined as discontinuing anti-Parkinson’s
symptom relief, such as through deep brain stimulation medication for at least 12 h) and motor complications,
(DBS). Over time, surgical approaches have evolved from such as motor fluctuations and dyskinesias, during the “on”
simple stimulation therapies to nerve nucleus destruction period (on-medication state, after taking anti-Parkinson’s
and, more recently, cell transplantation, providing PD medication).
patients with a broader range of treatment options. A positive outcome was defined as at least a 3-point
decrease in the motor disability score during the “off”
3.4.1. DBS period or the dyskinesia score during the “on” period.
DBS is a procedure that alleviates symptoms in PD patients After a 3-month follow-up, the positive outcome rate in
by implanting electrodes to stimulate specific brain areas, the experimental group was 69%, compared to 32% in the
such as the subthalamic nucleus (STN) or the globus pallidus control group. Furthermore, the experimental group showed
internus (GPi). The STN is the preferred target for stimulation, significant improvements in both MDS-UPDRS III (Motor
effectively controlling tremors, bradykinesia, rigidity, and Disability Score) and UDysRS (Dyskinesia Score) compared
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dyskinesia, while also enabling a reduction in medication to the control group. FUSA offers new hope for PD patients
dosage. In a clinical trial investigating DBS, PD patients due to its high safety profile, ease of operation, minimal
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were randomly assigned to two groups: The experimental side effects, and significant therapeutic effects. However,
group received bilateral STN DBS in addition to optimal drug technological challenges remain, such as ensuring precise
treatment (ODT), whereas the control group received ODT targeting and evaluating therapeutic outcomes. Further
alone. Subjects were followed for 2 years, mainly through research and exploration are needed to optimize FUSA’s
outpatient visits over the past 5 years. Compared with the application in PD treatment.
control group, the experimental group required less daily In addition to FUSA, surgical treatments for PD include
levodopa, and the probability of needing additional drug neuroablative surgery, neural implantable prosthetic devices,
treatment within 5 years was reduced to 0.06 times that of and cell transplantation. Surgical treatment for PD is a
the control group. Furthermore, the incidence of worsening complex process that requires individualized assessment by
clinical symptoms, such as resting tremor, was reduced to health-care professionals. Close monitoring of the patient’s
0.21 times that of the control group. These findings indicate condition and active collaboration between patients and
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that early STN DBS reduces medication dependency and clinicians is essential to achieve optimal therapeutic outcomes.
improves motor symptoms in PD patients.
3.5. Stem cell therapy
A meta-analysis examined the long-term (1 – 3 years)
effects of STN or GPi DBS on cognitive functions in PD Advances in technology and medicine have positioned
patients, primarily focusing on cognitive domains such stem cell therapy as a promising and innovative treatment

Volume 3 Issue 4 (2024) 6 doi: 10.36922/gtm.5082