Advancing cell therapy for neurodegenerative diseases

Cell-based therapies are being developed for various neurodegenerative diseases that affect the central nervous system (CNS). Concomitantly, the roles of individual cell types in neurodegenerative pathology are being uncovered by genetic and single-cell studies. With a greater understanding of cellular contributions to health and disease and with the arrival of promising approaches to modulate them, effective therapeutic cell products are now emerging. This review examines how the ability to generate diverse CNS cell types from stem cells, along with a deeper understanding of cell-type-specific functions and pathology, is advancing preclinical development of cell products for the treatment of neurodegenerative diseases

Neurodegenerative diseases of the CNS (the brain, retina, and spinal cord) affect all ages. They can range from congenital leukodystrophies that impair the white matter in childhood to those with increased prevalence during aging, such as Alzheimer's disease (AD), Parkinson's disease (PD), and age-related macular degeneration (AMD) (Figure 1). Mental illnesses may have a degenerative component, such as schizophrenia, which is characterized by cortical gray matter loss and signs of accelerated aging in patients.1 Some neurodegenerative diseases are prevalent, including AD, AMD, and PD, while others are rare, such as Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). These diseases may have genetic, environmental, or complex etiologies. Many neurodegenerative conditions progress to dementia, which is predicted to affect approximately 150 million people globally in 2050, with an economic burden of $10 trillion2,3 and untold costs to patients and their families. Although neurodegenerative diseases are currently incurable, for some, treatments are available to alleviate symptoms. A good example is PD, where levodopa (L-DOPA) administration and deep brain stimulation can improve quality of life, although these treatments do not address the underlying disease and its inexorable progression.