Regina Kelder

Hot Topic: Neuroinflammation (Video)

Research is growing in the links between neuroinflammation and a number of stubborn CNS diseases. Day one of our live Neuroscience 2019

For the last 25 years, research in Alzheimer’s disease has focused on amyloid as the key driver of disease pathogenesis. That all changed recently when several Phase III clinical trials targeting amyloid has reinforced the need to critically evaluate these trials and consider different approaches.One of those approaches now focuses on neuroinflammation, which may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites and autoimmumity. Nor is Alzheimer’s disease the only focus of neuroinflammation research. Scientists are also looking at this connect ion to stroke, Parkinson’s and brain injuries and Huntington disease, cancer as well as rare neurological diseases.

There are inherent challenges however in studying neuroinflammation preclinically—the start of all drug development. One of the most obvious challenges is figuring out how to induce neuroinflammation in research models to study its impact on the body and its response to drug candidates. There is also the ongoing challenge of making the findings from preclinical studies translatable to humans—one of the major reasons those amyloid beta drugs referenced earlier did not succeed in the clinic.

A provocative conversation filmed at Neuroscience 2019 delved into some of the issues. The Charles River Laboratories panel was led by Carmen Peritore, PhD, Product Manager, Neuroscience Discovery, Charles River, also included Tuulia Huhtala, PhD, PhD, Head of Biomarkers and Molecular Biology, Charles River.

A key way that neuroinflammation is studying is by using bacteria to induce a response—in this case the cellular membranes of gram-negative bacteria known as lipopolysaccharides. “They are basically activating multiple different immunological pathways, expression of cytokines and inflammatory cells,” says Dr. Huhtala, who is part of Charles River’s Finland team, which specializes in CNS Discovery. “They are mimicking the acute situation of the inflammatory processes.”

LPS is used to verify inflammation in an in vitro model and use the same technology in an in vivo model, says Huhtala.

In traumatic brain injury, one finds critical data to suggest the role of neuroinflammation. Scientists are learning that in cases where there are sustained repeat. Research has shown that sports-related head injuries can lead to future amyloid and tau pathology as well as a high risk of dementia. Three years ago, scientists from Johns Hopkins determined that the NFL players’ brains are replete with activated glial cells even without obvious neuropsychiatric problems. This finding suggests that neuroinflammation could be a marker for problems down the road,

Dr. Huhtaala says there are acute inflammatory responses seen right after a head injury or stroke, and then there are more long-term inflammatory responses. “So you need to ask, what the general pathological pathway of the disease itself is and determine how to select your model and most reasonable readout,” says Huhtala. “Nowadays we want to look at translational ways for the markers – that is more and more important.”

During Neuroscience 2019, drop by Booth 1043 to learn more about how Charles River is studying neuroinflammation, and other hot CNS topics. And follow the conversation on Eureka, Charles River’s science blog.