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Bringing in the proteome
February 2010
by Jeffrey Bouley  |  Email the author
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CAMBRIDGE, Mass.—Having recently paired up with Glendale, Calif.-based Applied Proteomics Inc., the ALS Therapy Development Institute (ALS TDI) notes that the two organizations in mid-December completed the first stage of a multi-year collaboration to identify and validate protein biomarkers associated with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The effort, which is jointly funded by ALS TDI and the Muscular Dystrophy Association (MDA), is intended to culminate in the creation of the an ALS biomarker initiative.

Their goal to identify and develop protein-based biomarkers for ALS is important to all the parties involved in no small part because biomarkers could be used to track the progression of ALS and help in developing effective therapeutics for the disease—of which none yet exist.

"The creation of protein biomarkers of ALS has the potential to not only hasten the creation of effective therapeutics, but also aid in the accurate measurement of their efficacy in people living with disease. This partnership is aimed to meet this need by leveraging the latest technology," says Dr. Steven Perrin, CEO and chief scientific officer of ALS TDI.

"We have perhaps the largest expression database around for ALS," Perrin adds. "Gene expression technologies are relatively inexpensive and fairly straightforward these days. But we needed to delve into the proteomics side to move forward to where we need to be, and that's trickier. Proteomics is far more expensive and complex. I dare say that gene expression work is almost 'cookie cutter' in sense now, but proteomics is still very much an art."

As such, ALS TDI didn't feel it would be able to handle the proteomics work, and teamed up with Applied Proteomics, which he notes is a new company, but one with a lot of expertise. Perrin says that academic labs had been under consideration initially as well, but a commercial partnership seemed like a better match.

"They are a small startup, we are a non-profit, and it was a good fit for where we are in this work and how we want to progress," Perrin says. "They are very motivated to see how their data might fit with our gene expression data, they aren't in any rush to go to humans right now. They want to really dig into the research."

"The absence of viable diagnostic and therapeutic tools for managing and treating ALS is tragic," says Dr. John E. Blume, chief science officer at Applied Proteomics. "We are delighted to be working in partnership with ALS TDI to address this problem by combining our systems engineering approach for proteomics-based biomarker discovery with their unique collection of focus, research talents, disease models and experimental data."

In this stage of the collaboration, ALS TDI provided Applied Proteomics with spinal cords from the SOD1 G93A mouse, a common preclinical model of ALS. Applied Proteomics isolates the proteins from these samples and investigates changes in protein expression using mass spectrometry, a process through which the expressions of individual proteins are quantified.

This data was then transferred back to ALS TDI, which is now in the process of comparing it to a similar proprietary database of RNA expression the Institute created in 2008. This proof-of-concept experiment is a crucial first step in order to determine the reliability of protein markers identified through the process.

There are currently no homogenous protein biomarkers of ALS. Phase II would look more closely at biomarkers in various tissue samples, such as blood and plasma.

The MDA's Augie's Quest Initiative is a major funder of ALS TDI, and provided the critical funding needed to execute this important collaboration. Perrin says ALS TDI sits at around $12 million for its annual budget right now, with about half that raised or secured by ALS TDI—including some U.S. Department of Defense funds because of a higher prevalence of ALS among military personnel—and the other half coming from Augie's Quest.

 
Code: E021019

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