Targeted Therapy of Multiple Sclerosis: A Case for Antigen-Specific Tregs.

Multiple sclerosis is an autoinflammatory condition that results in damage to myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing-remitting disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting potential to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Novel Non-invasive Transcranial Electrical Stimulation for Parkinson's Disease.

Conventional transcranial electrical stimulation (tES) is a non-invasive method to modulate brain activity and has been extensively used in the treatment of Parkinson's disease (PD). Despite promising prospects, the efficacy of conventional tES in PD treatment is highly variable across different studies. Therefore, many have tried to optimize tES for an improved therapeutic efficacy by developing novel tES intervention strategies. Until now, these novel clinical interventions have not been discussed or reviewed in the context of PD therapy. In this review, we focused on the efficacy of these novel strategies in PD mitigation, classified them into three categories based on their distinct technical approach to circumvent conventional tES problems. The first category has novel stimulation modes to target different modulating mechanisms, expanding the rang of stimulation choices hence enabling the ability to modulate complex brain circuit or functional networks. The second category applies tES as a supplementary intervention for PD hence amplifies neurological or behavioral improvements. Lastly, the closed loop tES stimulation can provide self-adaptive individualized stimulation, which enables a more specialized intervention. In summary, these novel tES have validated potential in both alleviating PD symptoms and improving understanding of the pathophysiological mechanisms of PD. However, to assure wide clinical used of tES therapy for PD patients, further large-scale trials are required.