“When your vision is to do what no one else has done, you need to develop creative and innovative strategies and teams to achieve the goal.”
— Roberta Diaz Brinton, PhD
In the 21st century, there is not a single therapeutic that cures a single neurological disease.
The success rate for development and approval for all CNS drugs designed to target etiology and symptoms of neurological disease is ~8%. Of those approved, all target symptoms and for a very small portfolio for multiple sclerosis can delay progression. None cure the neurological disease. Of the remaining 92% that fail, the vast majority of attrition occurs late in development, in Phase IIb and III clinical trials, and is principally due to a lack of efficacy.
Multiple factors contribute to the lack of CNS drug development success. Of these reproducibility and validity of basic science models that typifies academic research, the complexity of the aging process, the genetic and phenotypic diversity of affected population and the idiosyncratic progression of disease are all major contributors.
The poor reproducibility of preclinical discovery research and translational validity of animal models are two factors frequently cited for the high failure rate of CNS drugs during Phase II and III clinical trials. The prevailing paradigm in academic based therapeutic development is built upon the bench to bedside approach where a discovery at the bench is followed by a search for a potential disease application.
Age remains the greatest risk factor for multiple neurological diseases such as Alzheimer’s, Parkinson’s, traumatic brain injury, chronic pain and stroke. A critical factor in vulnerability to age associated disease is that aging occurs at the systems level making it a systems biology problem. The systems biology nature of aging and of neurological disease means that single target, single molecule strategies are unlikely to be successful.
Lastly, clinical development of therapeutics for the nervous system lacks genetic diversity. While health disparities is often seen through the lens of access to care, lack of genetic diversity in clinical therapeutic development means that surmounting barriers to access will not equate with medical success if therapeutics target only a small fraction of the diverse population. The impact of disparities in health and therapeutic care are greatest for chronic conditions requiring chronic drug therapy often for decades which is the norm for debilitating neurological diseases. Further, health disparities in underserved aged populations has a trans-generational ripple effect to adversely impact the familial and economic resources of caretakers already operating at the margin of sustainability.