Neurodegeneration: Focusing on root causes and interconnections
“Novel Perspectives on Neurodegeneration,” the first plenary session at ANA2022, takes place Sunday, October 23, from 9:15 to 11:30 a.m. Register now to attend the Annual Meeting in Chicago!
This symposium highlights cutting-edge research on holistic approaches to neurodegenerative disorders.
We talked to symposium chairs Krishnankutty Sathian, MBBS, PhD, FANA, Professor and Chair of the Department of Neurology at Pennsylvania State University College of Medicine, and Stefanie Geisler, MD, Assistant Professor of Neurology at Washington University School of Medicine in St. Louis, to learn about how appreciating the complexity and interconnectedness of neurodegenerative diseases can lead to better treatments.
Why is it important to approach neurodegenerative diseases in new ways?
Sathian: A lot of studies on neurodegeneration focus specifically on one disease or another. What we are trying to do in this symposium is take a step back and see if we can think about mechanisms that might be common across these neurodegenerative disorders. Also, it turns out that when people die and their brains are examined neuropathologically, many turn out to have multiple coexistent pathologies. If that’s true, then even if Alzheimer's is the most prominent, having treatments for that might not be enough. Is there something earlier in the causal chain that we need to target that may have more of an effect on multiple disorders?
Geisler: Yes, it's really about these common mechanisms. For instance, I work on axon degeneration. We now know that some of the mechanisms that lead to axon degeneration are the same in the peripheral nervous system and the central nervous system. We try to bridge the fundamental mechanisms that play a role in different neurodegenerative diseases in this symposium.
How else is a more integrated perspective important?
Sathian: Often, in this field as in many other fields, the majority of the studies have been done in white populations. There's really insufficient data to know if the factors that we identify are equally applicable to people from other ethnic backgrounds. In this session, Dr. Rita Guerreiro will be talking about genetic factors associated with neurodegenerative disorders including Alzheimer's and Parkinson's among different ethnic groups. Neurodegenerative disorders are occurring more frequently because we are living longer, and this is happening worldwide. If we have a global perspective, there could be a balance of factors such as diet that are different in certain groups, countries, or populations.
What is the practical impact of understanding shared disease mechanisms?
Geisler: As neurologists, we always want treatments. If we can target a fundamental shared mechanism, we can treat many different neurodegenerative diseases. This will be very far reaching.
Sathian: Exactly. For example, a protein called APOE4 has been recognized as a major genetic predisposing factor for Alzheimer's disease. But session presenter Dr. Holtzman’s got some interesting work suggesting that targeting this particular protein may also have beneficial effects for tauopathies implicated in other neurodegenerative disorders. This may help identify new approaches to treatment. There's been a lot of interest, in Alzheimer's disease, in targeting the amyloid cascade: this idea that amyloid is the first thing that goes wrong, leading to tau pathology and ultimately to neuron degeneration. But things are sort of cooking in the brain for 20 or 30 or more years before the disorder is recognized clinically, even in a prodromal form. We need to be thinking very differently about how we can identify these neurodegenerations earlier and target them in terms of treatment.
Geisler: As another example, axon degeneration is an early, fundamental mechanism in many neurological disorders, including peripheral neuropathies, several neurodegenerative CNS diseases, and traumatic brain injury. Exciting research over the past 10 years or so identified the central executioner of this axon degeneration pathway and how it is regulated. Several companies are now developing novel therapeutics targeting this molecule, called SARM1, including SARM1 inhibitors, SARM1–dominant/negatives, and antisense oligonucleotides, in order to treat a variety of different diseases. A promising new era has begun.