Immunotherapy for Neurodegenerative Movement Disorders

Neurodegenerative movement disorders represent a growing global health challenge. The most notable of these include amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and the synucleinopathies encompassing Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Recent advances in immunotherapy have opened new avenues for intervention in these devastating conditions. Protein aggregation and misfolding underlie the pathophysiology of these disorders. Immunotherapeutic approaches, such as vaccine-based strategies, monoclonal antibodies, and therapies that inhibit aggregation or enhance clearance, are being developed to target disease-specific protein aggregates, mitigating their toxic effects and offering potential disease-modifying treatments. Chronic neuroinflammation is a common hallmark of these disorders. Immunomodulatory agents, such as monoclonal antibodies against proinflammatory cytokines, hold promise in ameliorating inflammation-induced neurodegeneration. By dampening excessive immune responses, these therapies may slow disease progression and enhance neuronal survival. Finally, the role of T cells reacting to modified proteins and increased inflammation has gained prominent recognition as mechanisms for disease exacerbation and progression. Therapies that modulate T cell responses and infiltration into the central nervous system are thus under investigation. Immune checkpoint inhibitors and T cell reprogramming techniques may hold potential for halting the progression of these disorders by regulating immune-mediated damage. This chapter explores the emerging landscape of immunotherapeutic strategies, with a focus on neuroinflammation modulation, T cell targeting, and proteinopathy interventions. Immunotherapy for these disorders represents a promising frontier, offering more effective disease management and improved quality of life. Herein, we examine the research strategies aimed at immunotherapy for better clinical outcomes of these disorders. In light of the super-plethoric number of preclinical studies that focus on immune-based therapeutics for movement disorders, this chapter will limit discussions to those approaches that have initiated clinical transition or provided evidence of a transformative shift in strategic direction. Moreover, further research and clinical trials are essential to validate these innovative approaches and move closer to a future where these disorders can be successfully treated or even prevented.