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WILMINGTON, Mass.—Charles River Laboratories International, Inc. and the CHDI Foundation announced in April a five-year extension of the collaboration agreement under which the two organizations have been cooperating on discovering and developing treatments for Huntington’s disease (HD) since 2005. The collaboration thus far has allowed for the development of multiple preclinical proof-of-concept molecules for candidate drug targets and translational biomarker assays, the large-scale screening of several pharmaceutical companies’ small-molecule collections in HD patient-derived stem cell models to identify chemical starting points for drug discovery programs, and the validation of HD research models to use as industry standard tools.
 
Although the exact terms of the agreement have not been disclosed, the extension is designed to allow for greater integration of Charles River’s platforms into CHDI’s programs and permit more flexibility. The contract extension covers multidisciplinary services from across Charles River’s portfolio, including integrated biology and chemistry capabilities, complex primary neuronal assay development, high-content and fragment-based screening, computational chemistry, protein crystallography, and extensive in-vivo pharmacology approaches in research models for translational assessment.
 
Dr. Wilbert Frieling, corporate senior vice president of Global Discovery Services at Charles River, says the company has invested heavily in human stem cell platforms for drug discovery to support its work with CHDI. In addition, Charles River has begun investing in the use of CRISPR/Cas9 as a genome engineering tool for in-vitro drug discovery research.
 
“Our ultimate goal is to facilitate the identification of HD therapeutics and show efficacy for preclinical proof-of-concept molecules,” says Frieling. “We’re also characterizing new HD research models and applying new imaging techniques on existing preclinical HD models to measure the pharmacological effect of novel potential therapeutics.”
 
Frieling notes that rapid developments of in-vivo imaging techniques that support translational central nervous system (CNS) research include functional ultrasound as an in-vivo brain imaging technique—which allows imaging of awake animals—and positron emission tomography for in-vivo imaging in preclinical research to provide translational data on HD therapeutic strategies.
 
In addition, the expanded collaboration will allow the team the opportunity to more fully explore the cutting-edge developments in genomic research that show promise in HD applications.
 
“The recent identification of human genetic modifiers of HD age of onset as being part of the DNA repair pathways represents new potential therapeutic points of intervention,” Frieling tells DDNews. “The current focus is on developing assays and identifying tool compounds to test in relevant HD models.”
 
The CHDI Foundation and Charles River began their collaboration in 2005 and extended their contract in 2014. Also in 2014, Charles River acquired the contract research organization (CRO) services division of Galapagos NV, which included Argenta and BioFocus, providers of integrated drug discovery services. The acquisition equipped Charles River to offer full early-stage CRO services, with both integrated in-vitro and in-vivo capabilities from target discovery through preclinical development. The company has since employed these services in collaboration with CHDI to identify and develop HD therapeutics.
 
“Over time, CHDI and Charles River scientists have built a close scientific relationship of mutual trust and together have identified candidate HD drug targets and novel chemical entities, optimized CNS penetrance, developed proof-of-concept chemical tools, conducted cutting-edge assessments of targets and in-vivo assessments from DMPK to efficacy assessment in preclinical models, all the way to setting up highly translational readouts to predict the potential of HD drug candidates in humans,” Frieling reports.
 
“Charles River’s early drug discovery team has continuously delivered scientific expertise that enables our drug discovery research to produce more efficient results,” according to Robi Blumenstein, president of CHDI Management, Inc., in a media release announcing the extension. “We are excited to continue our research and work toward delivering a meaningful treatment to patients.”
 
“As an example of the close collaboration, several Charles River scientists meet with HD-affected families annually to provide a human perspective on the impact of their work,” adds Frieling. “Our team also actively works with CHDI to publish our mutual work and share the scientific discoveries to the wider HD research community.”
 
Huntington’s disease is a genetic neurological disease that causes the progressive dysfunction of nerve cells in the brain. About 200,000 cases are reported annually in the United States, often affecting younger patients in their 30s and 40s. The disease is caused by the expansion of a trinucleotide repeat and leads to a breakdown of nerve cells in the brain, causing cognitive, muscular and psychological deterioration.

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Volume 15 - Issue 5 | May 2019

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