Date: Aug 13, 2013 Author: Ron Leuty Source: bizjournals (
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A Stanford University spinout, backed by fresh research on how a common protein in the brain is involved in Alzheimer's disease, is aiming at a new target for drugs to block a range of neurodegenerative diseases.
Annexon Inc., started two years ago by Stanford neurobiology professor Dr. Ben Barres and Rinat Neuroscience founder Arnon Rosenthal, already has interest from potential Big Pharma partners. Now it has further proof from work in Barres' Stanford lab that a protein called C1q, which initiates an immune response called the "complement cascade" that rids the brain of dead cells or bacteria, accumulates at junctions where nerve cells meet in the brain.
The study, results of which were published Tuesday in the Journal of Neuroscience, indicates that elevated levels of C1q at these contact points, or synapses, may prime the junctions for death by the very immune cells meant to protect them.
The study, whose lead author was Alexander Stephan, was funded by the National Institute of Drug Addiction and Oracle Corp. boss Larry Ellison's Ellison Medical Foundation.
"In neurodegenerative disease, synapses start to massively degenerate," Barres said. "We think the complement cascade kills them."
That theory is like a vicious left turn at 100 miles an hour compared to how researchers and drug-development companies have thought about Alzheimer's over the past few decades. Billions of dollars have been spent — and the hopes of Alzheimer's patients and their caregivers dashed — in unsuccessful attempts to develop drugs that control or remove amyloid plaque that accumulates in the brain.
"The hypothesis is tested and disproven," Barres said.
Now Palo Alto-based Annexon, which has licensed several associated patent applications from Stanford, is closing in on drugs targeting the complement cascade, Barres said. The drugs could play a role in fighting back Alzheimer's, Barres said, as well as multiple sclerosis, glaucoma, Parkinson's disease, Huntington's disease and spinal muscular atrophy.
In all of those diseases, he said, "the neurons seem very vulnerable."
"What happens in these diseases, like Alzheimer's, is massive, progressive synapse loss and activation of the complement cascade," Barres said. "It's a no-brainer that blocking this cascade will block the neurodegeneration."
What's more, Barres said, there is some evidence that such a block may actually help restore some brain function lost to the diseases.
Annexon has received funding from Boston-based venture capital firm Fidelity Biosciences, according to a 2011 Securities and Exchange Commission filing. It is seeking funding to carry it through for another six months or so, until it can cut deals with Big Pharma partners.
The Stanford lab's work has been funded by about $400,000 in federal government research cash plus the same amount from foundations, Barres estimated.
The lab started studying glial cells — those that provide protection for neurons — or as Barres calls them, "the other cells in the brain that everyone ignores." That's how the lab "stumbled upon" the complement cascade, on which it has concentrated for about 10 years.
"We didn't start by (looking at) what's causing synapse degeneration," Barres said. "This is often the way it happens in science."
