Toward a Disease-Modifying Therapy of Alpha-Synucleinopathies: New Molecules and New Approaches Came into the Limelight.

The accumulation of the various products of alpha-synuclein aggregation has been associated with the etiology and pathogenesis of several neurodegenerative conditions, including both familial and sporadic forms of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). It is now well established that the aggregation and spread of alpha-synuclein aggregation pathology activate numerous pathogenic mechanisms that contribute to neurodegeneration and, ultimately, to disease progression. Therefore, the development of a safe and effective disease-modifying therapy that limits or prevents the accumulation of the toxic intermediate products of alpha-synuclein aggregation and the spread of alpha-synuclein aggregation pathology could provide significant positive clinical outcomes in PD/DLB cohorts. It has been suggested that this goal can be achieved by reducing the intracellular and/or extracellular levels of monomeric and already aggregated alpha-synuclein. The principal aim of this review is to critically evaluate the potential of therapeutic strategies that target the post-transcriptional steps of alpha-synuclein production and immunotherapy-based approaches to alpha-synuclein degradation in PD/DLB patients. Strategies aimed at the downregulation of alpha-synuclein production are at an early preclinical stage of drug development and, although they have shown promise in animal models of alpha-synuclein aggregation, many limitations need to be resolved before in-human clinical trials can be seriously considered. In contrast, many strategies aimed at the degradation of alpha-synuclein using immunotherapeutic approaches are at a more advanced stage of development, with some in-human Phase II clinical trials currently in progress. Translational barriers for both strategies include the limitations of alpha-synuclein aggregation models, poor understanding of the therapeutic window for the alpha-synuclein knockdown, and variability in alpha-synuclein pathology across patient cohorts. Overcoming such barriers should be the main focus of further studies. However, it is already clear that these strategies do have the potential to achieve a disease-modifying effect in PD and DLB.

Therapeutic effect of "Zhishen-Tiaosui" acupuncture for the stroke patients with unilateral spatial neglect / 国际中医中药杂志

Objective To explore the clinical efficacy of "Zhishen-Tiaosui" acupuncture treatment for the stroke patients with unilateral spatial neglect. Methods A total of 66 patients who met the inclusion criteria were randomized into two groups, 33 in each group. The control group was treated with conventional body acupuncture, and the treatment group was treated with Zhishen-Tiaosui acupuncture treatment. Both groups were treated for 20 days and followed up for 8 weeks. The Fugl-Meyer Assessment (FMA) was used to assess limb motor function, and the Catherine Bergego Scale (CBS) was used to assess the daily living ability and the extent of unilateral spatial neglect. The Modified Barthel Index (MBI) assesses the ability of daily living and evaluates clinical outcomes. Results After treatment, FMA (39.21 ± 8.96 vs. 26.34 ± 8.06, t=6.135), MBI (49.62 ± 10.19 vs. 40.18 ± 9.52, t=5.919) in the treatment group were significantly higher than those in the control group (P<0.01), CBS (9.55 ± 4.68 vs. 18.20 ± 6.97, t=3.889) were significantly lower than those in the control group (P<0.01). Treatment group brain regions in the left frontal back, the left inferior frontal gyrus, left occipital in back to back to back to before the left temporal and temporal, left and right side of the anterior cingulate, back in the right frontal, cingulate gyrus of the left side, left precuneus activation intensity were significantly higher than the control group (t=4.615, 3.052, 3.644, 3.575, 3.152, 2.816, 2.579, 3.511, P<0.01). The total effective rate was 78.8% (26/33) in the treatment group and 54.5% (18/33) in the control group. The difference between the two groups was statistically significant (χ2=5.657, P=0.017). Conclusions The Zhishen-Tiaosui can improve the blood circulation of the brain in the unilateral space of the stroke, enhance the cognitive function and exercise capacity, and improve the daily living ability.