The CHDI Foundation is providing reagents, domain knowledge, and funding to help companies reposition their predevelopment compounds and failed drug candidates as potential therapeutics for Huntington Disease (HD).
The foundation works with an international network of scientists to discover and develop drugs that slow the progression of HD. It seeks to accelerate the discovery process by serving as a “collaborative enabler” encouraging the development of practical ideas, useful research materials, and powerful technologies, often by providing financial support.
Hyunsun Park, Ph.D., director, translational biology at CHDI, described the foundation’s in vitro/in vivo assay platforms, as well as the capabilities of its clinical team to help biotech and pharma companies reposition drugs as potential HD treatments.
CHDI has built an extensive list of target molecules implicated in HD pathogenesis, according to Dr. Park, who explained that “one of CHDI’s approaches to validate these targets is to interrogate the function of these targets using pharmacological tools. We have been reaching out to various biotech and pharmaceutical companies that have compounds that were developed against some of the targets with a view to establishing collaborations to test their efficacy in HD preclinical models.”
CHDI has implemented cellular and ex vivo HD models to measure electrophysiological or cellular read-outs that are manifested by expression of mutant huntingtin protein.
CHDI has also funded multiple research projects to develop HD transgenic animals, including rodents and larger mammals such as sheep, mini-pigs, and primates. “We continuously characterize and evaluate the transgenic animals in order to come up with outcome measures that are most relevant to HD pathophysiology and then develop test batteries that can be applied for compound development,” Dr. Park explained.
Unique elements of preclinical bioassays, for example, include in vitro and in vivo assays, “that truly reflect the cellular dysfunction or disease progression caused by mutant huntingtin protein. For example, we have been using chronic, neurodegenerative HD transgenic rodent models for preclinical testing. It takes six months to two years to evaluate a single compound in various test batteries including motor, behavior, cognitive, as well as brain imaging.”
“An important part of what CHDI does involves directing our own research programs; we don’t simply give out funding and reagents to third parties. CHDI employs science directors who drive their own projects aimed at specific molecular targets that look promising in HD. Although we don’t have our own wet labs we use CROs to carry out research directed by CHDI’s scientists.”
The foundation formed an outreach team about a year ago and has been in discussion with firms to assess the possibility of testing their compounds in HD preclinical models and potentially repositioning for HD indication. “None have advanced to the clinic as yet, but we are hopeful that will change in the next year or two," Dr. Park added.