The title was selected because the book reviews stories that have given Parkinson’s and Alzheimer’s diseases their meaning as unique diseases. But, after dissecting the source data, the story that emerged was very different from the one known about the diseases.
“Hence, the compelling unifying stories defining neurodegenerative diseases are biologically fictional,” Espay notes.
About 80 million people worldwide are afflicted with neurodegenerative diseases. Despite extensive research, there still are no approved medications to slow or stop the progress of these diseases.
The authors argue that there really isn’t “a” Parkinson’s disease, but in actuality many diseases.
“We neurologists are very protective of what we are doing and like to reassure the public that if we keep the course, we will find a cure for Alzheimer’s, and one for Parkinson’s, continuously feeding a false narrative, a false hope. We only pay lip service to the idea that Parkinson’s is truly many diseases. Or that Alzheimer’s is a syndrome. We acknowledge the many-diseases fact as if it were an inconvenient disclaimer while continuing to work as if Parkinson’s and Alzheimer’s are each a multiheaded beast soon the conquered. This cognitive dissonance –with all the financial and human costs it brings—has to end,” Espay says.
So, the pair wrote Brain Fables to jolt the public “because we need an outraged public to force the change we need,” he says. Espay, who also holds the James J. and Joan A. Gardner Family Center for Parkinson's Disease Research Endowed Chair, hopes that clinicians and researchers begin to look differently at these neurodegenerative diseases, but believes it will only come if the public revolts with both patients and advocates asking for change.
“Only pressure from the outside will be successful as pressure from within gets drowned by the convenience of continuing to trust in the century-old model of neurodegenerative diseases and in the low-risk, low gain approach to funding research.”
Espay admits that since starting to write the book in the spring of 2019, he has changed the course of his own research. For example, he no longer participates in ongoing infusion studies using antibodies against synuclein, the protein that accumulates in Parkinson’s disease. In the book, he reviews the evidence from infusion trials of antibodies against amyloid, the protein that accumulates in Alzheimer’s disease. Two decades and 35 negative trials later, the strategy has proven futile at best, harmful at worst. He also recently launched the Cincinnati Cohort Biomarker Program, which is the first phenotype-agnostic longitudinal cohort in neurodegenerative diseases. In this work, all analyses are anchored not on the symptoms of a group but on the unique biology of individuals with disease.
“We are not asking, ‘what is different between people with versus without tremor’ but rather, ‘who are the individuals with a given mitochondrial marker reduced two standard deviations below the mean?’ and ‘who are those positive for the bioassay of X therapy, available for repurposing of that therapy?’” he says “The latter aspect is a key component. We are not interested in simply determining the many biological subtypes of disease, but in identifying those who could benefit by virtue of a link between their biology and the mechanism of action of a therapy already available.”
A parallel effort will be to develop serum bioassays for such future repurposing efforts in biologically suitable individuals. Although there are many anticipated (and unforeseeable) challenges, this study aims at “walking the talk” by moving from learning about diseases to learning about people with diseases, he points out.