Technology to Assess Neurons Gives New Life to San Diego’s Afraxis
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that it is really collaborative,” Stengone said in a telephone call. “We have formed a joint governance committee to oversee everything, and we’re working on downstream [drug discovery] milestones.”
The new Afraxis technology significantly advances neuroscientists’ ability to rapidly analyze dendritic spines—the pinhead-like protrusions along the neuron’s cell body, Stengone said. The technology also has comes at a time when researchers have begun to correlate the size and density of dendritic spines with strong synaptic activity—which in turn is strongly associated with learning, memory, and cognition.
The new Afraxis system, named the Enhanced Spine Platform, can analyze about 250,000 dendritic spines per month. That is both fast and accurate enough to be used in drug discovery, Stengone said. The technique wasn’t practical before now, he explained, because it would take an academic lab using conventional technology six to nine months to analyze 3,000 to 5,000 dendritic spines. That was a method that took too long and did not generate enough data to ensure accuracy.
“What we’ve been able to do is change the paradigm for dendritic spine analysis and characterization,” Stengone said. In developing drugs for CNS disorders, scientists must often rely on behavioral measures to assess whether or not a prospective drug is effective.
He said the potential value of technology that relies on more objective measurements became apparent after a group of German scientists published a 2009 study of two promising drugs (known as gamma-secretase inhibitors) for treating Alzheimer’s disease.
At the time, Eli Lilly was developing the gamma-secretase inhibitor semagacestat to reduce the buildup of harmful amyloid plaques in Alzheimer’s patients. But the German group’s study revealed a potential adverse side effect—the drugs also dramatically reduced the density of dendritic spines in the neurons of mice.
Lilly terminated its semagacestat program nearly a year later—after preliminary findings from two late-stage clinical trials involving more than 2,600 patients showed that the drug appeared to accelerate patients’ cognitive decline as well as their ability to perform daily activities.
“It was very compelling data,” Stengone said. Taken together, the German study and the adverse results of Lilly’s semagacestat program indicated that a drug could cause abnormalities in dendritic spine size and density—and that, in turn, could result in negative cognitive effects.
Since then, Stengone said additional studies have suggested that dendritic spine abnormalities underlie many CNS disorders, including autism, schizophrenia, and Alzheimer’s.
At Afraxis, Stengone and others concluded that the company’s technology could become a valuable litmus test for Big Pharmas as they select specific compounds from a portfolio of CNS drug candidates as the ones that would be most likely to succeed in clinical trials.