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The Michael J. Fox Foundation Awards $1.1M for Validation of Parkinson's Disease Therapeutic Targets

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The Michael J. Fox Foundation for Parkinson’s Research has announced $1.1 million in total funding to six different projects aimed at validating potential therapeutic targets for Parkinson’s disease.

Target validation is an essential phase of drug development, yet a lack of funding for validation studies has long been a major roadblock to the efficient translation of promising discoveries into practical therapies for PD.

The Foundation’s Target Validation initiative, one of MJFF’s Edmond J. Safra Core Programs for PD Research, provides intellectual and financial resources to this area of the drug development pipeline, helping to advance potential PD drug targets toward clinical trials and Parkinson’s patients.

Four of the projects announced aim to determine whether a molecule or biological pathway is a true target for therapies that can protect brain cells from the effects of PD. One project, led by Claudio Hetz, PhD, of the University of Chile is studying a pathway that helps to reduce cellular stress, called the Unfolded Protein Response (UPR), as a potential therapeutic target.

Under a 2008 MJFF Rapid Response Innovation Award, Dr. Hetz’s team demonstrated that an essential factor of the UPR is associated with neurotoxicity in pre-clinical models. With further MJFF funding, Dr. Hetz will continue to advance this area of research.

The remaining two projects are focusing on targets that have the potential to alleviate dyskinesias, the excessive, uncontrollable movements associated with long-term dopamine replacement therapy. One awardee, Andrea Giuffrida, PhD, of the University of Texas Health Science Center at San Antonio is using the FDA-approved drug rosiglitazone to investigate a cellular factor, called peroxisome proliferator-activated receptor gamma, as a potential target for treating dyskinesias. The possibility of providing evidence of the efficacy of rosiglitazone as a PD treatment is especially attractive as already approved drugs can advance much more rapidly into clinical testing.

The following is a complete list of funded projects:

• PHD Inhibition as a Potential Novel PD Neuroprotectant
Julie K. Andersen, PhD, Buck Institute for Age Research, Novato, California

• VEGF-B: A New Neurotrophic Factor for Treatment for Parkinson's Disease
Torsten Falk, PhD, University of Arizona, Tucson

• mTORC1 as a Target for the Treatment of L-DOPA-induced Dyskinesia
Gilberto Fisone, PhD, Karolinska Institutet, Stockholm, Sweden

• Peroxisome-proliferator Activated Receptor Gamma as a Target for Anti-dyskinesia Pharmacotherapy
Andrea Giuffrida, PhD, University of Texas Health Science Center at San Antonio

• Targeting the Unfolded Protein Response (UPR) Transcription Factor XBP-1 to Treat Parkinson’s Disease
Claudio Hetz, PhD, of University of Chile, Santiago, Chile

• Modulation of the Rho-Kinase Pathway for Improvement of Regeneration in PD
Paul Lingor, MD, University of Goettingen, Germany.