Huntington’s Neurodegeneration May Be Caused by Rampant Immune Processes

Converging evidence suggests that neurodegenerative conditions, such as Huntington’s disease, are caused by persistent inflammatory immune processes that ultimately kill neurons. This insight, presented by researchers at University of Adelaide, Australia, might change the way researchers approach drug development for neurodegenerative diseases and possibly alter the trajectory of unsuccessful attempts during recent decades.

Immune surveillance functions are crucial for the body to protect it from infection and to detect and respond to pathogens. If such a response goes awry, becoming auto-inflammatory, it turns on and kills healthy cells.

The study, published in the journal Frontiers in Neuroscience, argues that the immune process gone rampant is the underlying mechanism similar to various neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s, depending on which neuronal cell types are affected by disease.

“Dementia, including the most common form Alzheimer’s Disease, and related neurodegenerative conditions are dramatically rising in frequency as people live longer and our population ages,” said lead author Robert Richards, a professor at the university’s School of Biological Studies in a press release. “Currently we have no effective treatments to assist the millions of affected people, and these diseases are an enormous burden on families and the public health care system.”

While research has focused mainly on protein deposits in neurodegeneration, Richards believes that focus should be redirected to uncontrolled innate immunity. He gathered the evidence for his theory in the study “The Enemy within: Innate Surveillance-Mediated Cell Death, the Common Mechanism of Neurodegenerative Disease.“

“Our interest in the body’s own (innate) immune system as the culprit began when we discovered that immune system agents become activated in a laboratory model of Huntington’s Disease,” he said. “Remarkably, researchers from other laboratories were at the same time reporting similar features in other neurodegenerative diseases. When we pulled the evidence together, it made a very strong case that uncontrolled innate immunity is indeed the common cause.”

Such uncontrolled immune processes can occur as a result of an array of circumstances that include genetic mutations, infection, toxins or physical injury.

“We hope this new way of understanding neurodegeneration will lead to new treatments,” said Richards. “We now need to further investigate the immune signaling molecules, to identify new drug targets that will delay the onset and, or halt the progression of these devastating diseases.”