Personalized Medicine in Parkinson’s Disease: New Options for Advanced Treatments

Mishima, Takayasu; Fujioka, Shinsuke; Morishita, Takashi; Inoue, Takeshi; Tsuboi, Yoshio

doi:10.3390/jpm11070650

Cited by 6 publications

(6 citation statements)

References 99 publications

(141 reference statements)

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“…The pharmacotherapy of PD relies on dopamine level restoration, and although good management of symptomatology is commonly achieved, this balance is maintained for only a short period of time, as complications related to medication may occur, thus impacting tolerability and treatment efficacy ( Jankovic, 2002 ; Tambasco et al, 2018 ). Numerous therapeutic alternatives have been developed to ameliorate the symptom impact and disability associated with the disease and its first-line pharmacology options ( Mishima et al, 2021 ; Serva et al, 2022 ). In fact, different rTMS modalities are considered a potential therapy for PD, given the safety and lack of side effects after application ( Wagle Shukla et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study

Rashid-López,

Macías-García,

Sánchez-Fernández

et al. 2023

Front. Aging Neurosci.

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Background and objectivesIntermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.MethodsA total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.DiscussionThe findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

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Section: Discussionmentioning

confidence: 99%

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study

Rashid-López,

Macías-García,

Sánchez-Fernández

et al. 2023

Front. Aging Neurosci.

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“…These 17 patients all met the United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria (UKBBC) and had been diagnosed with sporadic PD by a specialized neurologist ( Hughes et al, 1992 ). Furthermore, all patients were preoperatively suffering from motor complications that: were difficult to control with a combined drug and exercise regimen; had shown >33% improvement in a total score obtained in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS Part III) in response to the levodopa challenge test (LDCT) that compared assessment during the off-stage and after taking levodopa; and were without prominent cognitive impairment [Mini-Mental State Examination (MMSE) score < 24] ( Mishima et al, 2021 ). Concerning the programming, we follow the basic programming concept ( Volkmann et al, 2002 ).…”

Section: Methodsmentioning

confidence: 99%

Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson’s Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study

Hayashi

Mishima

Fujioka

et al. 2022

Front. Hum. Neurosci.

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IntroductionDeep brain stimulation (DBS) is an effective treatment for advanced Parkinson’s disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.Materials and MethodsSeventeen patients with Parkinson’s disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome.ResultsSignificant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores.DiscussionUnilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.

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“…Thus, the circulation of information is needed (Figure 4), and it takes teams of clinicians and basic researchers worldwide to achieve such breakthroughs [102,103]. In the clinical setting, a team approach in device-based therapies is widespread [104,105], and the need for a team approach is recognized in the treatment of Parkinson's disease [106]. Rare neurodegenerative diseases require the involvement of even more professions.…”

Section: Team Approach For Perry Diseasementioning

confidence: 99%

Perry Disease: Bench to Bedside Circulation and a Team Approach

Mishima,

Yuasa-Kawada,

Fujioka

et al. 2024

Biomedicines

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With technological applications, especially in genetic testing, new diseases have been discovered and new disease concepts have been proposed in recent years; however, the pathogenesis and treatment of these rare diseases are not as well established as those of common diseases. To demonstrate the importance of rare disease research, in this paper we focus on our research topic, Perry disease (Perry syndrome). Perry disease is a rare autosomal dominant neurodegenerative disorder clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. The pathological classification of Perry disease falls under TAR DNA-binding protein 43 (TDP-43) proteinopathies. Patients with Perry disease exhibit DCTN1 mutations, which is the causative gene for the disease; they also show relatively uniform pathological and clinical features. This review summarizes recent findings regarding Perry disease from both basic and clinical perspectives. In addition, we describe technological innovations and outline future challenges and treatment prospects. We discuss the expansion of research from rare diseases to common diseases and the importance of collaboration between clinicians and researchers. Here, we highlight the importance of researching rare diseases as it contributes to a deeper understanding of more common diseases, thereby opening up new avenues for scientific exploration.

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Personalized Medicine in Parkinson’s Disease: New Options for Advanced Treatments

Cited by 6 publications

References 99 publications

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study

Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson’s Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study

Perry Disease: Bench to Bedside Circulation and a Team Approach

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