In the wake of amyloid beta, companies eye tau and neuroinflammation as Alzheimer’s drug targets. Live from Neuroscience 2019
The World Health Organization estimates that there are now around 50 million people with dementia. Every year, we add 10 million more cases.
It is not overstating to describe this disorder as a public health crisis. The disease is draining, both financially and emotionally, to the families dealing with this horrible condition. There are few if any drugs able to control symptoms and slow progression of disease.
Alzheimer’s disease, the most common form of dementia afflicting 44 million worldwide, is a perfect case in point. For years researchers pursued a single strategy—trying to clear the brain of clumps of beta amyloid protein that form the plaques integrally linked to the disease. That effort came to a grinding halt last year when pivotal Phase III trials failed to stop or reverse the dementia.
While it was clear that amyloid plaques were a pathologic hallmark of Alzheimer’s disease, it was less clear whether treating the plaques would actually do patients any good.
Where the field should go from here was the subject of a video conversation at Neuroscience 2019 between Carina Peritore, PhD, Product Manager, Neuroscience Discovery, Charles River and her colleague, Maria Herva Moyano, PhD, Group Leader Neuroscience, Charles River who specializes in dementia.
Dr. Moyano said it was unsurprising that researchers embraced the amyloid beta theory is a known genetic link to Alzheimer’s. “All the work done on cellular assays and animal models all pointed in the same direction,” says Dr. Moyano.
Where to go from here is the question many companies are now pondering. Some companies are focusing on tau, a protein that, in Alzheimer’s disease, forms threads that stick together in tangles inside neurons, sandbagging their communications with one another. “There are quite a lot of bio and pharma companies looking at different approaches of getting rid of pathological tau. These include antibodies against phosphorylated tau and PROTACs to get rid of the protein,” said Dr.Moyano.
Companies are also looking at targeting neurinflammation that is the cause of nerve cell death and synaptic dysfunction. Instead of being a mere bystander activated by emerging senile plaques and tau tangles, neuroinflammation contributes as much if not more to the pathogenesis as do plaques and tangles, researchers say.
Some strategies are designed to stop chronic inflammation without suppressing microglia function, which is important to brain activity. Other strategies inhibit tau phosphorylation kinases or reduce oxidative injury.
“There are many cases of dementia where we don’t know what triggers the disease,” says Dr. Moyano. “If you look at neuroinflammation that is something that underlies many neurodegenerative diseases. By trying to understand and do more research we could potentially have a therapeutic not just on Alzheimer’s but on many other diseases.”
Toward that end, Charles River is partnering with the UK Dementia Consortium, which is bringing together academics, pharma and CROS. Their mission: To find new therapeutic targets and perhaps an effective therapy for the tens of millions of patients living with dementia.
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.