NEWYORK, NY -- The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded $1.5 million to fund seven projects that each aim to validate therapeutic drug targets for Parkinson’s disease. The Target Validation initiative is the first in a series of funding efforts under the Foundation’s Drug Discovery and Development program, designed to accelerate the rate at which new Parkinson’s therapies are brought to market.
“Developing marketable therapies is an intricate process that requires extensive screening and testing of potential targets before they can be brought to the clinical development stage,” said Ken Olden, chief scientific advisor for MJFF. “This program supports the applied science critical to legitimizing identified drug targets, and opens the door for the later phases of research that will eventually bring these therapies to patients.”
Target validation is a key step in the drug discovery process that employs compound screens and animal models to determine whether a molecular target is critically involved in a disease and to ascertain whether this target can be modified in a way that affects disease symptoms and progression. Advances in research, technology and genomics have increased the number of promising therapeutic targets for Parkinson’s disease; however neither academics nor industry has devoted sufficient resources to validate them. This dearth of funding has impeded the development of marketable therapies
“The Foundation has taken the lead in validating some of the most promising molecular targets, increasing the likelihood that some will yield new therapies for Parkinson’s,” said Deborah W. Brooks, MJFF president and CEO. “We believe that this program could serve to jumpstart the R & D process, as industry seeks to further develop promising results.”
Three of the awardees will target alpha-synuclein, a compound which frequently aggregates in people with Parkinson’s. Despite this association, there is not consensus as to whether alpha-synuclein aggregation plays a direct role in loss of dopamine neurons in the brain; thus, validation of alpha-synuclein is vitally important to the field. Of the three grants, one will use rodent models to target and modulate several cellular pathways that are hypothesized to block the toxic effects of a mutated form of alpha-synuclein. The other two grants will look more specifically at ways to lower alpha-synuclein levels or prevent its ability to aggregate.
Although current drug approaches for relieving Parkinson’s symptoms generally target the dopamine signaling system in the brain, side effects from this approach such as uncontrollable dyskinesias can be problematic. Two grants will look at non-dopamine signaling pathways in the brain as potential targets for symptomatic therapies. One project will focus on a novel target, trace amine receptors, while another grant recipient will study the metabotropic glutamate receptor, mGluR7. The hope is that both targets can provide improved symptomatic relief without causing debilitating side effects. Another funded project will focus on other forms of the metabotropic glutamate receptor that may be useful for treating levodopa-induced dyskinesias.
Finally, other targets to be studied by grant recipients in this program include poly(ADP-ribose) glycohydrolase (PARG), believed to play a critical role in the midbrain neuronal death associated with Parkinson’s.
The following is a complete list of researchers who were awarded grants under the Target Validation initiative:
Patrick Aebischer, PhD
Ecole Polytechnique Federale de Lausanne (EPFL)
Testing of Small Molecules in Alpha Synuclein Rat Model of PD
David Bumcrot, PhD
Alnylam Pharmaceuticals
In vivo Target Validation: RNA Interference to Silence Alpha-Synuclein in PD Mouse Models
Angela Cenci-Nilsson, PhD
LundUniversity
Metabotropic Glutamate Receptors in L-Dopa-induced Dyskinesia
P. Jeffrey Conn, PhD
VanderbiltUniversityMedicalCenter
Discovery of Allosteric Potentiators of mGluR7 as Novel Antiparkinsonian Agents
Anthony L. Fink, PhD
University of California, Santa Cruz
Validating Toxic Protein Aggregation as a Therapeutic Target in PD
Raul R. Gainetdinov, PhD
DukeUniversity
Screening of Small Molecule Libraries to Identify Trace Amine Receptor Ligands Active in Treatment of Parkinson’s Disease
Paul J. Hergenrother, PhD
University of Illinois
Inhibitors of Poly (ADP-Ribose) Glycohydrolase (PARG) as Novel Agents for the Treatment of Parkinson’s Disease