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Parkinson Disease: 5 Updates

Pain related to more severe motor symptoms, phosphodiesterase 10A loss seen early, novel therapy shows promise, and other recent findings are summarized here.

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Parkinson pain related to more severe motor symptoms, phosphodiesterase 10A loss seen early, novel therapy shows promise-these are some of the latest findings in Parkinson disease research. Scroll through the slides for concise summaries of key studies.

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Parkinson pain related to more severe motor symptoms.Researchers used a semi‐structured interview, the Brief Pain Inventory, and the Pain Disability Index to identify and characterize pain in a consecutive series of 292 patients with Parkinson disease.1 Close to three-fourths of patients reported pain, classified as musculoskeletal (63%), dystonia‐related (27%), central parkinsonian (22%), and/or radicular or neuropathic (9%).

Pain was related to more severe motor symptoms, anxiety symptoms, and comorbidities. The patients with the central parkinsonian subtype of pain had lower levodopa responsiveness for non‐axial motor symptoms, greater responsiveness of pain to antiparkinsonian treatment, and other distinct demographic and clinical features. The findings may suggest a more integrated approach to motor and non‐motor symptoms in clinical care for patients with Parkinson disease and pain.

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Phosphodiesterase 10A loss seen early in Parkinson disease. Loss of phosphodiesterase 10A is associated with a gradual and progressive increase in motor symptoms, a study showed.2 Participants underwent [11C]IMA107 PET, [11C]PE2I PET, and 3‐Tesla MRI scans. Early de novo PD patients showed loss of [11C]IMA107 and of [11C]PE2I binding in the caudate and putamen. Early L‐dopa–treated PD patients showed additional loss of [11C]IMA107 in the caudate and putamen but loss of [11C]PE2I only in the putamen.

Longer disease duration corresponded with lower [11C]IMA107 in the caudate and putamen and with lower [11C]PE2I only in the putamen. Higher burden of motor symptoms correlated with lower [11C]IMA107 in the caudate and putamen and with lower [11C]PE2I only in the putamen. The authors suggested that phosphodiesterase 10A imaging shows potential for following disease progression similar to that of dopamine transporter imaging.

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Novel therapy for Parkinson disease shows promise. Noting that cytoplasmic accumulation of α-synuclein (SNCA) protein is a characteristic pathological feature of Parkinson disease, researchers designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide that targeted SNCA with improved stability and cellular uptake in vivo.3 AmNA-ASO downregulated SNCA at the mRNA and protein levels in vitro and in vivo. AmNA-ASO was delivered into the mouse brain by intracerebroventricular injection without additional chemicals, and administration of AmNA-ASO ameliorated neurological defects in Parkinson disease model mice expressing human wild type SNCA. AmNA-ASO shows promise as a therapeutic strategy for SNCA-associated pathology in patients with Parkinson disease.

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Acupuncture has protective effect on dopaminergic neurons. In a systemic analysis of the neuroprotective effect of acupuncture in animal models of Parkinson disease, outcome measures included tyrosine hydroxylase (TH) level and dopamine content.4 The results showed statistically significant effects of acupuncture for increasing both TH levels and dopamine content compared with those observed in control groups. Acupuncture treatment also mitigated motor dysfunctions exhibited by model Parkinson disease animals. The authors concluded that in spite of limitations in the number and quality of the included studies, their results suggest that acupuncture exerts a protective effect on dopaminergic neurons in rodent models of Parkinson disease.

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A psychosocial approach for dementia in Parkinson disease. Because drug-based therapies for Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) are moderately effective and not always tolerated, researchers evaluated the feasibility, acceptability, and tolerability of a psychosocial approach, Cognitive Stimulation Therapy (CST) for persons with PDD or DLB and their care partners (CST-PD).5 They randomized patients with PDD, DLB, or mild cognitive impairment in PD and their care partners to 12 weeks of treatment as usual or CST-PD.

More than 90% of 76 consenting participant-dyads undertook discrete sessions of greater than 20 minutes’ duration, although the average number of sessions completed was lower than the recommended dose. Intervention acceptability ratings (interest, motivation, and sense of achievement) were high. No serious intervention-related adverse events were reported. The authors concluded that psychosocial interventions for PDD and DLB are acceptable and well tolerated.

References
1. Vila-Chã N, Cavaco S, Mendes A, et al. Unveiling the relationship between central parkinsonian pain and motor symptoms in Parkinson's disease. Eur J Pain. 2019 May 9. doi: 10.1002/ejp.1413. [Epub ahead of print]

2. Pagano G, Niccolini F, Wilson H, et al. Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson’s disease. Mov Disord. 2019 Jun 3. doi: 10.1002/mds.27733. [Epub ahead of print]

3. Uehara T, Choong CJ, Nakamori M, et al. Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson’s disease. Sci Rep. 2019 May 21;9(1):7567. doi: 10.1038/s41598-019-43772-9.

4. Ko JH, Lee H, Kim SN, Park HJ. Does acupuncture protect dopamine neurons in Parkinson’s disease rodent model?: a systematic review and meta-analysis. Front Aging Neurosci. 2019 May 8;11:102. doi: 10.3389/fnagi.2019.00102. eCollection 2019.

5. McCormick SA, Vatter S, Carter LA, et al. Parkinson’s-adapted cognitive stimulation therapy: feasibility and acceptability in Lewy body spectrum disorders. J Neurol. 2019 Jun 4. doi: 10.1007/s00415-019-09329-6. [Epub ahead of print]

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