As life expectancy is projected to increase in the ensuing decades, individuals of older age continue to exceed the previous generation’s lifespan. Advancing age is associated with a reduction in physical and mental functional capacity, and chronic inflammation is a major factor contributing to this decline. A heightened inflammatory state can lead to exhaustion, weakness, weight loss, slow gate speed, and an overall decrease in activity level. These phenotypes define the onset of the disease process known as frailty. Frailty is a growing epidemic, which severely undermines a person’s ability to deal with outside stressors, and increases their rate of hospitalization, institutionalization, and mortality. Current interventions focus on preventative care by improving exercise capacity, strength, nutritional supplementation, diet, and mobility. However, a biological cure has heretofore remained elusive. Here, we introduce the novel therapeutic principle that mesenchymal stem cell (MSC) therapy may represent a safe, practical, and efficacious both the treatment and prevention of frailty in individuals of advancing age. To date, a phase I safety trial reveals an excellent safety profile and suggests that mesenchymal stem cells can ameliorate signs and symptoms of frailty. These early studies lay the groundwork for future large-scale clinical trials of this exciting and novel therapeutic concept that has the potential to expand health span in the aging population.
Part of the book: Frailty and Sarcopenia
This chapter will review the unique aspects and limitations of the design of phase I/II (safety and efficacy) clinical trials of stem cell therapy. Although the classical pharmacologic principles applicable to drugs are not applicable to biologic (live cell) therapeutic agents, an important stage in the development of any new therapeutic agent is the establishment of an optimal dosage and delivery route. This can be particularly challenging when the treatment is a biologic agent, such as stem cells, that may exert its therapeutic effects via complex or poorly understood mechanisms. To date, clinical studies have shown inconsistent findings regarding the relationship between cell dose and clinical outcomes. This can be at least partially attributed to variations in donor cell type, source, characteristics, dosing/concentration, delivery route, underlying mechanisms of action, and efficacy endpoints tested. The current recommendations will be reviewed herein to give new investigators a general understanding of the unique issues that need to be considered and addressed when designing a stem cell therapy phase I/II clinical trial.
Part of the book: The Management of Clinical Trials