Proteostasis, with San Diego Roots and Boston Home, Seeks Edge in Alzheimer’s and Parkinson’s

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Peter Reinhart, the new chief scientist of Cambridge, MA-based Proteostasis Therapeutics, spent the last six years leading one of the top neuroscience groups in the pharmaceutical industry, at Wyeth. The group has gotten its share of press for its efforts, with mixed results, to take aim at neurodegenerative scourges like Alzheimer’s and Parkinson’s.

But Wyeth’s $68 billion megamerger with Pfizer closed last year, and priorities started getting shuffled around in a massive R&D organization. One of the first things the new parent company did was close down Wyeth’s neuroscience operation in Princeton, NJ. For Reinhart, it was time to look around for something early, edgy, and with potential for bigger impact than a big company is willing to take a flier on. He says he’s found it with Proteostasis.

“Pharma, in a way, is chasing a number of targets that have been validated over and over again. Some of the shakeout you see happening in pharma right now is because there is so much overlap with a lot of companies chasing the same few targets,” Reinhart says. “In part what attracted me to Proteostasis is that we are entering uncharted water. We have the potential to create innovative novel targets, and innovative therapies that really are unique.”

Proteostasis burst on the biotech scene back in September 2008 when it raised a massive, $45 million initial round of venture capital from HealthCare Ventures, Fidelity Biosciences, New Enterprise Associates, Novartis Option Fund, and Genzyme Ventures. The founding science came from the San Diego labs of Jeffery Kelly at The Scripps Research Institute and Andrew Dillin at the Salk Institute for Biological Studies, and Richard Morimoto at Northwestern University.

Peter Reinhart

Peter Reinhart

The money, and the talent, is being directed toward biology that seeks to alter protein pathways that break down as people age, possibly leading to neurodegenerative diseases like Alzheimer’s and Parkinson’s. Proteostasis sees itself navigating the complex steps by which proteins that have already been synthesized based on genetic instructions are made fully functional and stable and are transported to their appropriate locations in the cell. Sometimes these pathways degrade as we age and cause neurodegenerative diseases. While we are young and healthy, we might produce amyloid plaques, for example, but a network of proteins works to dispose of them. One theory is about Alzheimer’s is that as we age, this garbage disposal capacity weakens, amyloid plaques build up, and we get neurodegenerative changes.

I sat down with Reinhart and Proteostasis co-founder Jeff Kelly a few weeks ago during a visit to Kelly’s lab at The Scripps Research Institute in San Diego. This is still very early stuff, and they offered none of the timetables biotech companies usually trot out about how they have drugs poised for the clinic in the next year or so. As Reinhart says, they are pursuing completely new targets, with conventional oral pills, that will seek to restore a sense of protein network balance—or proteostasis, as the name suggests—that should restore the functions people have for disposing of plaques thought to cause Alzheimer’s.

Some of these new targets, Kelly says, appear to be implicated in more than one disease. So if you restore protein network balance with an eye toward treating Alzheimer’s, your drug could also provide a benefit for another disease like Parkinson’s.

Before people get carried away, the company isn’t talking about creating silver bullets … Next Page »

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