Michael J. Fox Foundation Seeks Novel Drug Development Strategies for 2007 Target Validation Initiative
Wed Oct 4, 1:58 PM ET

http://news.yahoo.com/s/usnw/2006100...tiative140_xml

NEW YORK, Oct. 4, /PRNewswire-USNewswire/ -- The Michael J. Fox Foundation for Parkinson's Research today announced the launch of its 2007 Target Validation effort. This annual program is designed to validate the therapeutic potential of various scientific discoveries and push them one step closer to the clinic. The 2007 program will provide up to $2 million in funding to validate therapeutic targets for Parkinson's disease.

An increasing number of promising cellular pathways and therapeutic targets have been identified, but translation of scientific discoveries into actual therapeutic interventions requires narrowly focused applied validation studies. Work that will develop strategies to manipulate a biological target or pathway, or test the beneficial effects of manipulating that target in relevant PD model systems, is required to move research along. These fundamental and often underfunded steps of the therapeutics development process are the focal point of Target Validation.

"The foundation's strong focus is on providing funding for translational research that can drive PD drug development and the delivery of better treatments to patients that much faster," said Deborah W. Brooks, president and CEO of The Michael J. Fox Foundation. "Target Validation is key to these efforts because of its potential to accelerate the pace of drug discovery and to encourage industry investment in Parkinson's."

The 2007 program, which follows the model of the annual Target Validation initiative, seeks investigator-initiated applications to validate therapeutic targets to address aspects of Parkinson's disease including:

-- neuroprotective strategies focused on slowing or preventing the process of neuronal death;

-- neuroregenerative/neurotrophic strategies to restore or slow the deterioration in neuronal function;

-- targets or pathways to improve the treatment of motor symptoms of PD;

-- targets or pathways to treat non-motor symptoms of PD, including cognitive dysfunction, autonomic dysfunction, sleep disorders, or depression;

-- targets or pathways to alleviate complications of PD treatment including dyskinesias.

In mid-October, the foundation will announce a new initiative, Novel Approaches to Drug Discovery for Parkinson's Disease, which complements the Target Validation program. Similar to Target Validation, this program provides critical resources for underfunded stages of the drug development process. It also reflects the foundation's emphasis on bridging early discovery work and late-stage translational research to "de-risk" industry investment in new PD therapeutics. While Target Validation provides funding to validate promising potential therapeutic approaches for PD, Novel Approaches picks up where Target Validation leaves off and focuses exclusively on targets whose potential benefit has already been demonstrated in at least one animal model of Parkinson's. Information about Novel Approaches will be available on the Foundation's Web site, http://www.michaeljfox.org beginning Oct. 11.

Target Validation pre-proposals are due by Dec. 13, and funding is anticipated by spring 2007. Proposals not deemed appropriate for Target Validation may, at the Foundation's discretion, be considered for Novel Approaches if they are within the scope and intent of that program. For more information, visit the foundation's Web site.

To date, The Michael J. Fox Foundation for Parkinson's Research has funded more than $78 million in research aimed at finding a cure for the disease, either directly or through partnerships.


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Contact: Michelle Schwartz, 212-509-0995 ext. 248 or mschwartz@michaeljfox.org or Mark Frasier, Ph.D., 212-509-0995 ext. 244 or mfrasier@michaeljfox.org , both of the Michael J. Fox Foundation

Hi, this is my first post here but some of you may remember me from the other site. I have been an advocate of Low Dose Naltrexone to stop the progression of Parkinson's. I have been taking 4.5 mg of naltrexone for (low doses of Sinemet and Mirapex too) for about 28 months now and I can't say my PD is worse.
I emailed the MJF site mentioned here with information on LDN and, while a Phd did respond, I believe I got a non-response or no interest at all. It would seem to me that there is reason to believe LDN does stop disease progression, in addition, it is an FDA approved drug, it's cheap and has few side effects. I also included a research paper with work done on naloxone (naltrexone is similar) showing how these opioid (antagonists?) could work in being neuro-protective. LDN is available now, what is the MJF intent? Are they looking to fund research on very expensive treatments which may not be available for many years?
Ashley

A report from the NIH on Naloxone (naltrexone):
The purpose of this study was to identify two neuroprotective compounds with a similar bimodal dose response, to discern whether the neuroprotective characteristics of each compound could converge into a single mechanism, and through this process, to elucidate a common femtomolar site of action.

Parkinson’s disease (PD) is characterized by the specific and progressive death of dopaminergic neurons in the substantia nigra (SN); other neuronal cell types are much less affected. Recent reports have linked inflammation to neurodegenerative disease, where microglia, cells of myeloid lineage responsible for innate immunity in the brain, are considered to be the major cell type underlying the inflammation-mediated neurotoxicity (7 8 9) . The activation of microglia is a complex process involving the release of several soluble proinflammatory factors [tumor necrosis factor {alpha} (TNF-{alpha}), PGE2, IL-1] and free radicals (nitric oxide, superoxide) (7) . Current replacement therapy with L-dopa is able to alleviate disease symptoms, but is unable to alter the disease course. Thus, therapeutic interventions designed to inhibit the microglial inflammatory response offer hope for attenuation of the neurodegenerative disease process. The current anti-inflammatory treatments available, including steroids and nonsteroidal anti-inflammatory drugs, are limited by the ability to influence only a small portion of the microglial response (10) . Thus, identification of compounds acting on novel targets to inhibit the release of a wide range of proinflammatory factors from overactivated microglia is of paramount importance. In the ensuing study, we report that femtomolar concentrations of naloxone and the peptide fragment glycine-glycine-phenylalanine (GGF) attenuate a broad spectrum of the microglia inflammatory response (reactive oxygen species (ROS) and proinflammatory factors) and are neuroprotective with extremely potent efficacy through the inhibition of microglial NADPH oxidase.
http://www.fasebj.org/cgi/content/full/19/6/550
http://www.lowdosenaltrexone.org/index.htm