Neuroprotective Therapies with Magnetoelectric Nanodiscs for Parkinsonian Symptoms

Parkinson’s disease (PD), the most common neurodegenerative motor disorder in the world, affects 2-3% of the world’s population over the age of 65. PD is characterized by the loss of dopaminergic neurons in the mid-brain region called substantia nigra and symptoms such as resting tremors, bradykinesia, slowed gait, and postural instability¹. The current gold standard of surgical care for PD patients is subthalamic nucleus deep brain stimulation (STN DBS), which has been shown to bring tremor symptoms under control. However, because of the invasive nature, increased risk, side effects, and exclusive patient criteria for the electrode-based DBS, this treatment option is primarily applied only to late-stage PD patients at an average of 14 to 15 years after diagnosis^2-4. In this study, we present a promising, less invasive alternative with magnetoelectric nanodiscs (MENDs)-based STN DBS. MENDs are composed of Fe₃O₄-CoFe₂O₄-BaTiO₃ with a double-core-shell structure to generate electric polarization in the piezoelectric shell strained by the magnetostrictive core under biologically benign magnetic fields. The treatment effects of the MEND- and electrode-based stimulations are compared by assessing the motor deficits and locomotion in Parkinsonian mice (6-OHDA mouse model). We have developed deep-learning methods to analyze the locomotion and investigate the characteristic gait properties of the mice with Parkinsonian symptoms. Furthermore, since electrode-based STN DBS potentially delays the progression of PD when performed at an earlier stage^5-8, we examine whether MENDs slow down disease progression possibly with neuroprotective effects. These results indicate that treatment with MEND-based STN DBS for early-stage PD holds the potential to pave the way to novel neuroprotective therapies.<br/><br/><br/>1. Poewe, W. et al. Parkinson disease. <i>Nat</i><i>.</i> <i>Rev.</i><i>. Dis</i><i>.</i> <i>Primers</i>, <b>3</b>, 17013 (2017).<br/>2. Kleiner-Fisman G. et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. <i>Mov Disord.</i>, <b>21</b>(suppl 14), S290–S304 (2006).<br/>3. Volkmann J. et al. Long-term results of bilateral pallidal stimulation in Parkinson's disease. <i>Ann Neurol.,</i><b>55</b>, 871–875 (2004).<br/>4. Houeto JL. et al. Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. <i>Arch Neurol., </i><b>57</b>, 461–465 (2000).<br/>5. Musacchio, T. et al. Subthalamic nucleus deep brain stimulation is neuroprotective in the A53T alpha-synuclein Parkinson’s disease rat model. <i>Ann. Neurol.</i> <b>81</b>, 825–836 (2017).<br/>6. Hacker, M. L. et al. Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes. <i>Neurology</i> <b>95</b>, e393–e401 (2020).<br/>7. Merola, A. et al. Earlier versus later subthalamic deep brain stimulation in Parkinson’s disease. <i>Parkinsonism Rel. Disord.</i> <b>21</b>, 972–975 (2015).<br/>8. Schuepbach, W. M. et al. Neurostimulation for Parkinson’s disease with early motor complications. <i>N. Engl. J. Med.</i> <b>368</b>, 610–622 (2013).