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Chasing Memory / Final of four parts

Success, with a big dose of rejection

Gary Lynch expects his lab's work to bring 'all the tribes of neuroscience to the same campfire.' But he meets resistance.

August 22, 2007|Terry McDermott | Times Staff Writer

Vadim Fedulov, a graduate student, was assigned to run the rats in a maze in the odor-learning experiment. He had been in the lab for just a couple months. Lynch had agreed to take him on when it looked as if he might be tossed out of grad school altogether. He was young, very bright, somewhat unpredictable and not punctual at all. He was, in other words, a typical Lynch recruit.

One morning not long after, before the markets opened, Cortex announced the results of a clinical trial in which the ampakine CX717 had been given to adults diagnosed with ADHD. The results were an unqualified success. The drug reduced ADHD symptoms across the board, almost equal to existing medications -- mainly stimulants -- without any of their deleterious side effects.

ADHD affects an estimated 4% of children in the United States. More than 30 million prescriptions are written for the disorder annually.

Cortex stock doubled in value over the next week. Chief Executive Roger Stoll announced the company was in negotiations with at least eight big pharmaceutical companies that wanted to license CX717. Such a deal, Stoll said, would be worth immediately as much as $30 million to the company and eventually several hundred million dollars.

Lynch was ecstatic. It was the first big public demonstration of the power of the ampakines. This was a day he had waited 15 years for.

"It's immensely gratifying. It really is," he said. "It validates the principle that you can treat neurological diseases by increasing cortical communication."

Lynch, feeling magnanimous, patched up his relationship with the university and moved back to 101 Theory. Kramar received a job offer from an Irvine biotech company. Although she hated the timing, in tears, she took the job.

Danielle Simmons took over her role in the engram search. Fedulov built his T-maze -- which was outfitted with sliding doors and flashing lights and apertures through which he inserted cotton swabs soaked in various scents -- and began running rats.

Lynch was scheduled to speak at a pharmaceutical conference in San Francisco. He prepared to be welcomed as a conquering hero.

Two days before the conference, the FDA called Cortex and said it had found unspecified problems in preclinical results -- that is, lab tests on animals -- with CX717. It ordered an immediate halt to all human trials.

Monday morning, as Lynch was scheduled to speak, the clinical hold was announced. Lynch had a bronchial infection and was loaded with antibiotics and steroids; his plane was two hours late because of bad weather. Cortex stock fell 60%. The subject of Lynch's talk was the failure of translation from preclinical lab work to clinical trials in memory drugs.

Irony wasn't quite strong enough to describe the circumstances.

Lynch had no objection to the FDA's action, even though he thought the hold would be resolved painlessly. "They're doing what they have to do," he said. "We're putting stuff in people's brains, and they should be careful."

Lynch returned to Irvine, the lab and the odor-learning experiment.

Fedulov had trained three rats and was ready to inject the dye and have the brains prepared for examination. Two of the rats, for reasons unknown, died from the injections. The sole remaining rat was sacrificed, its brain sliced and set on slides. Fedulov had the slides at 101 Theory. Lynch wanted to look at them at Gall Lab, where Lauterborn, an expert microscopist, could read and photograph the images. He called Fedulov and asked that he bring the slides.

Tracey Shors, a neuropsychologist from Rutgers who early in her career had written a much-discussed paper casting a skeptical eye toward the role of LTP in memory, happened to be on the UCI campus. She and Lynch were old friends and met to discuss their various researches. Lynch told her about the afternoon's prospects; she was interested, but skeptical. Bring me an engram, she said. Bring me an engram.

Lynch went to lunch, just about dying from anxiety. When he returned, Fedulov was nowhere to be found. There was Lynch, the big experimental result waiting -- no rat brains, no scientists.

"You'd think I was trying to launch the space shuttle," he said.

Lynch called Fedulov on his cell. He'd come and gone and left the slides in a refrigerator, neglecting to tell anyone. To further darken the atmosphere, a short paper Lynch had written describing the preliminary results of this work had come back from a journal editor, declined with scathing reviews.

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