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New book argues that Parkinson’s disease is actually many diseases

Dr. Alberto Espay co-authors book on neurodegenerative diseases

In a new book scheduled to be published Aug. 24, Alberto Espay, MD, professor in the University of Cincinnati College of Medicine's Department of Neurology and Rehabilitation Medicine, argues that current understanding of Parkinson’s disease and other neurodegenerative diseases is actually impeding the medical community’s ability to find cures for these diseases.

“We know so much about ‘Parkinson’s disease’ and about ‘Alzheimer’s disease,’ but so little about the people who have symptoms attributed to these diseases. If we let the data accumulated speak, we would see that the current models we have created for Parkinson’s and Alzheimer’s apply to virtually no one. We propose this is why every clinical trial aimed to slow each of these diseases has failed. The main message is that unless we change the way we think and approach brain aging conditions, we will continue to have failure after failure,” Espay says.

The book Brain Fables was co-authored by Benjamin Stecher, 36, who was diagnosed with Parkinson’s disease seven years ago. The two connected almost two years ago when Stecher was traveling the world interviewing scientists working on understanding Parkinson’s. Stecher maintains a blog, Tomorrow Edition.(Stecher’s Jan. 21, 2019 interview with Espay can be heard here.) Espay, whose expertise is in Parkinson’s disease and movement disorders, has not treated Stecher.

“Ben had grown skeptical about the direction of research efforts and found like-minded skepticism in me,” Espay says. “We discovered we had reached many of the same conclusions about a variety of research data from our separate vantage points. The many conversations that ensued became the source of Brain Fables.”

cover of the book Brain Fables

Cover of Dr. Espay's new book.

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.

Dr. Alberto Espay stands on a glass bridge inside the UC College of Medicine.

Alberto Espay, MD, shown in the UC College of Medicine. Photo by Colleen Kelley/UC Creative + Brand

Espay added that the thought and discussion involved in writing the book brought a lot more humility and honesty to his clinical work. “I have to admit to a patient I may be diagnosing with Parkinson’s that I actually don’t know what ‘disease’ he or she truly has.”

Espay hopes that readers of the book come to understand that diseases that only exist in our imagination and which “make sense to us but not to biology” can never be cured. However, people whose biological abnormalities can be identified and selectively targeted, can be cured.

“We view this book as an opportunity to have a frank discussion about what we know, but more importantly, about what we think we know but don’t,” Espay says. “We don’t want to remove hope, we want hope to be based on rational elements.”

The book, which is subtitled The Hidden History of Neurodegenerative Diseases and a Blueprint to Conquer Them, is published by Cambridge University Press.

Featured photo of Alberto Espay, MD, by Colleen Kelley/UC Creative + Brand.