Foundations that support efforts to find treatments for rare diseases have stepped in to fill a significant funding gap caused by increasingly conservative venture capitalists and constraints at large pharmaceutical companies. Their considerable financial (in the tens of millions of dollars for many foundations) and intellectual involvement has triggered collaborative translational drug discovery efforts. CHDI Foundation, a virtual biotech exclusively focused on the discovery and development of drugs for Huntington's disease (HD) is one such organization.

Our enterprise is privately funded with a mandate to fast-track possible therapies for HD. Hence, CHDI strives to support all aspects of the drug development process from early exploratory efforts to identify and validate targets, to the screening, medicinal chemistry, preclinical optimization, on through the clinical and regulatory aspects of evaluating candidate molecules in human trials. Without wet-labs and staffed by more than forty individuals who bring a wealth of scientific, medical, business, legal...

The challenge we face is to facilitate and expedite the sharing of research tools and results among academic and industrial HD investigators while protecting publication rights and the ownership of intellectual property. Our support to academic researchers is structured similarly to that provided to our corporate partners: through contracts. Investigators provide periodic progress reports that may be shared, in confidence, with other scientists; deliverables include access to any reagents and non-exclusive licenses to any intellectual property (such as assay system protocols) developed under a contract. To encourage research related to HD, all such reagents are quality controlled and made publicly accessible via a centralized repository (

University laboratories provide insights which allow us to identify and validate the targets, mechanisms, pathways, and networks that are the most relevant intervention points for HD. Once a target has been selected, we stress early proof-of-concept experiments since, unlike other drug discovery units, our singular focus on HD prevents us from opportunistically moving into alternate indications.

A network of fee-for-service contract research organizations (CROs) provides the brick-and-mortar laboratories and skilled staff to execute CHDI-sponsored drug development activities. In some cases, these efforts may be assembled from individual experiments (formulation, pharmacokinetic studies, blood-brain barrier penetration) at different places; but they also include semi-integrated programs in which iterative cycles of chemical synthesis and biological annotation drive structure-activity-relationships for projects at the lead optimization phase. Other programs, anti-sense against huntingtin for example, are conducted as joint ventures with biotech partners.

Preparation for clinical trials is proceeding along with efforts to develop therapeutics. These studies are an invaluable resource for developing biomarkers and rating scales and, in the near future, for therapeutic trials recruitment. CHDI has provided support for selected interventional trials which, to date, have only tested nutriceuticals or attempted to repurpose existing drugs. Our strong belief is that de novo development of NCEs (new chemical entities) will be necessary for a true disease-modifying therapy for HD. Our great hope is that once we have de-risked candidate HD therapies by demonstrating preliminary efficacy, that they will be attractive in-licensing opportunities for the large pharmaceutical companies who are much better poised to fund and conduct the later stage development activities.

Looking from the industrial and academic edges of the translational research chasm, any effort to build a bridge seemed daunting, but looking up from the basin, we saw an opportunity. Our solution: Provide a scaffold that can adapt to changes in the landscape and incorporate the combined knowledge and strengths of all the parties involved.

Robert E. Pacifici is Chief Scientific Officer and David P. Rankin is Chief Legal Officer of CHDI.

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