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KineMed and CHDI Foundation Extend Collaboration on Huntington's Disease Biomarkers

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NEW YORK (GenomeWeb News) – KineMed said this week that it has extended its collaboration with the CHDI Foundation on research into biomarkers for Huntington's disease.

Under the agreement the company will use its mass spec-based Dynamic Proteomics platform to perform global discovery of proteins linked to Huntington's with the ultimate goal of identifying biomarkers that can be used to monitor the efficacy of treatments for the disease, Patrizia Fanara, KineMed's vice president of neuroscience, told ProteoMonitor.

The two parties launched their collaboration in 2012. That initial phase focused on measuring the in vivo dynamics of the huntingtin protein, a mutated version of which is responsible for Huntington's disease. That study also looked at a pathway involved in axonal transport, investigating whether alterations in that pathway might be used as markers for the disease.

In the second phase of the collaboration, KineMed and CHDI plan to expand their analysis beyond the axonal transport pathway "to look at many pathways simultaneously in an unbiased approach," Fanara said.

While protein marker work typically begins with broad discovery work and then proceeds to more targeted analysis, the KineMed-CHDI collaboration has moved in the opposite direction. The initial work focused primarily on links between axonal transport and the disease. Company scientists in collaboration with University of California, San Francisco researchers demonstrated in a 2012 study in the Journal of Clinical Investigation that axonal transport deficits were involved in other neurodegenerative diseases including Parkinson's. With this in mind, Fanara said, they sought to explore potential links to Huntington's.

Having established through use of its Dynamic Proteomics platform that this pathway was, indeed, altered in Huntington's cases, the researchers are now searching for other pathways that could be involved.

The huntingtin protein "interacts with many different components from many different pathways," Fanara said. "So by using our platform we have validated one key causal pathway, and now we want to ask the question of how many other pathways are affected in the disease."

The thinking, she said, is that most likely Huntington's patients will not all have the same clinical phenotype, and so different markers will be required to track the efficacy of treatment in different patients.

"That is the core of personalized medicine," she said. "We don't want to be limited. We want to query the system as an entire network, not just a single pathway."

KineMed's Dynamics Proteomics platform uses wide-scale isotopic labeling combined with mass spectrometry to track the kinetics of protein activity, providing insight into biological pathways and disease processes. The system requires subjects – either animal or human – to ingest deuterium or another stable isotope labeled tracer, which is then incorporated into proteins made by the subject. By measuring these labeled proteins via mass spec, the firm is then able to study not just protein expression but also the dynamics of a target pathway, including information on protein synthesis and breakdown rates and transport.

KineMed typically uses Agilent QTOF instruments for this work, but the company has also in the past used Orbitrap systems from Thermo Fisher Scientific.

Ultimately, Fanara said, the CHDI collaboration aims to develop clinical markers for monitoring the efficacy of treatments for Huntington's. An assay measuring the microtubule dynamics pathway studied in the first phase of the project is already in clinical use for Parkinson's disease, she said, adding that the company hopes to publish a paper on this work in the near future and move the assay into the clinic for Huntington's "as soon as possible."

The collaborators have not yet determined what anti-Huntington's agent they will develop efficacy markers for, Fanara said, noting that CHDI "has a number of agents [targeting the huntingtin protein] in development."

The foundation, she said, "wants to test as many [agents] as they can first, and then discuss which one [the parties will make] the focus of the extended collaboration."

Last year KineMed entered a related collaboration with CHDI and Isis Pharmaceuticals to develop companion biomarkers for tracking response to therapy in Huntington's. Under the collaboration, KineMed was to provide Isis with pharmacodynamic biomarkers for use in the development of an antisense drug for the disease.

This work is still ongoing, Fanara said. However, she noted the Isis drug would not necessarily be investigated in the phase of the collaboration announced this week.

Huntington's affects roughly 30,000 people in the US, and there are currently no approved therapeutics for slowing progression of the disease.

Fanara declined to provide a timeline for the second phase of the collaboration or give details on the sharing of intellectually property arising from the work or other financial terms of the deal.

In addition to its Huntington's work, KineMed is involved in several other collaborations in neurodegenerative disease. In October 2013, the company signed a deal with Amgen to study protein homeostasis in neurodegenerative diseases, tracking the synthesis and clearance rates of pathogenic brain proteins. Also last year, KineMed entered an agreement with MedImmune to study the effects of a monoclonal antibody on the dynamics of a cellular prion protein implicated in conditions including Creutzfeldt-Jakob disease and Alzheimer's. In 2012, the company received $1.2 million from the Michael J. Fox Foundation for the development of biomarkers for Parkinson's.

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