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Cellumen, ADDF to Co-Develop Cellular Models, ID Biomarkers for Alzheimer’s

Cellumen this week announced that it has penned an alliance with the Alzheimer’s Drug Discovery Foundation to create a cellular model of the disease.
Cellumen will seek to develop an assay and other tools that can help researchers understand how drugs may better work against β-amyloid processing, the chief neural component responsible for the disease’s characteristic memory loss.
Terms of the partnership call for Cellumen to develop “cellular systems biology tools” for the Alzheimer’s disease research community, including a panel of biomarkers that can trace how the disease progresses in a cellular model, Kate Johnston, Cellumen’s vice president for discovery programs, told CBA News this week.
Cellumen will also develop a set of cellular models that represent regulatation of tau protein expression, and a protein-protein interaction biosensor for studying a tau activity regulator.
The goal is to end up with a set of reagents, a neuron cell line, a biosensor, and a cellular systems biology panel of assays that can help researchers evaluate the activity of the tau-activation space as a lead generation strategy.
The agreement was signed in the summer and will run through the early part of next year, Johnston said. Financial details were not disclosed.
Although the ADDF is funding the project, Cellumen will own the IP that results from it. “We have done projects in the past where the IP that we own in terms of some of the reagent class types or cell lines we give exclusivity to, but that is on a case-by-case basis,” Cellumen CEO Lansing Taylor told CBA News this week. “In general, however, we want to make these tools available to all.”
“Cellumen fits our profile because we believe that their technology can accelerate drug discovery for Alhzeimer’s disease in a very unique way, and that is why we are looking forward to working with them on this project,” said Howard Fillit, executive director of the ADDF.

“This is part of our strategy of seeing the increased linkage between drug discovery … and discovery toxicology that is applied very early on in the development process.”

In Alzheimer’s disease β-amyloid is thought to be toxic to the neurons in the brain, which causes the disease’s characteristic memory loss, though it remains unclear how β-amyloid is processed within the cell.
“We believe that Cellumen, by developing the kind of assays that they plan to develop, will help us to understand how drugs that may affect β-amyloid processing will work, and what compartments of the cell will be important in creating effective drugs,” Fillit said. 
The project has three specific goals. “We have begun by identifying the set of cellular biomarkers that can be put into an assay that really best interrogates the tau activity state in the cells,” Johnston said. The second aim, which is scheduled to be completed in the first quarter of 2009, is to develop a cell line in which the expression and activation of wild-type and mutant tau could be manipulated.
The third goal, which is also scheduled to be completed in the first quarter of 2009, is to develop a protein-protein-interaction biosensor that could capture the activity of the CDK5 kinase, which is an upstream regulator of the tau phosphorylation state. The phosphorylation state of tau is connected to the aggregation of tau and the toxicity of tau in neuronal cells.
This is Cellumen’s first collaboration with the ADDF. The company has also been involved in a large Alzheimer’s disease grant at the University of Pittsburgh’s Center for Excellence in Detection, Diagnosis, and Intervention in Dementia, and has worked with the Cure Huntington’s Disease Initiative and the High Q Foundation since February 2006 (see CBA News, 2/24/2006).
Cellumen also participates in a spinal muscular atrophy project that is being driven by the US National Institute of Neurological Disorders and Stroke.
“We have had, from almost the beginning of Cellumen, a focus on building tools that would progress some of these complex neurodegenerative diseases,” said Johnston.
“This is part of our strategy of seeing the increased linkage between drug discovery, especially with more sophisticated cellular models of disease, and discovery toxicology that is applied very early on in the development process,” Taylor said, adding that the use of more sophisticated cellular models of disease in drug discovery should give researchers better leads.
Taylor said that this agreement is an example of Cellumen’s linkage between early drug discovery and early drug development, and takes advantage of the company’s strength in drug discovery in what it calls “measure and manipulate.”
In this protocol, Cellumen manipulates a particular cellular activity, measures it with reagents, and builds a cellular systems-biology profile around that model, Taylor said.

“Using this approach, we can launch an attack on really intractable targets, or those that have been intractable in the past,” he added.

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