Can Innovative Trial Designs in Orphan Diseases Drive Advancement of Treatments for Common Neurological Diseases?

Global regulatory agencies have transformed their approach to approvals in their processes for formal review of the safety and efficacy of new drugs. Opportunities for innovation have expanded because of the coronavirus disease 2019 (COVID-19) pandemic. Several regulatory-led initiatives have progressed rapidly during the past year, including patient-focused drug development, model-informed drug development, real-world evidence, and complex innovative trial designs. Collectively, these initiatives have accelerated the rate of approvals. Despite demands to focus on urgent needs imposed by the COVID-19 pandemic, the number of new drug approvals over the past year, particularly for rare diseases, has outpaced expectations. Advancing therapeutics for nervous system disorders requires adaptive strategies that align with rapid developments in the field. Three relentlessly progressive diseases, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and Parkinson's disease are in urgent need of new treatments. Herein, we propose new regulatory initiatives, including innovative trial designs and patient-focused drug development that accelerate clinical trial conduct while meeting critical regulatory requirements for therapeutic approval.

Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging.

PURPOSE OF REVIEW: Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline. RECENT FINDINGS: Currently, our cognitive health span does not match our life span. Age-related cognitive impairment and preventing and treating ARCI will require an in-depth understanding of the interrelated risk factors, including individual genetic profiles, that affect brain health and brain aging. Hypertension and cardiovascular disease are important risk factors for ARCI. And, many of the risk factors for developing hypertension, such as diabetes, smoking, stress, viral infection, and age, are shared with the development of ARCI. We must first understand the mechanisms common to the converging risk factors in hypertension and ARCI and then design person-specific therapies to optimize individual brain health. The understanding of the convergence of shared risk factors between hypertension and ARCI is required to develop individualized interventions to optimize brain health across the life span. We will conclude with a discussion of possible steps that may be taken to decrease ARCI and optimize an individual's cognitive life span.