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Drug Discovery 2014 -- by ELRIG - Manchester UK

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Joined together by JNK
April 2012
by Ashley Abraham  |  Email the author

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JUPITER, Fla.—The Scripps Research Institute has announced a global license agreement with OPKO Health granting OPKO exclusive rights to develop, manufacture and commercialize a novel compound that could potentially abate the devastating effects of Parkinson's disease. The compound, SR 3306, inhibits a class of enzymes called c-jun-N-terminal kinases (JNK) that are essential to neuron survival. If successful, SR 3306 could be the first treatment to prevent, slow or halt the progression of Parkinson's disease.
 
Parkinson's is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra, a part of the brain involved in motor control.  The dopamine-transmitting neurons of the substantia nigra are responsible for inhibiting motor behaviors. As a result, the loss of these neurons renders those with Parkinson's disease unable to control their motor movements.  
 
JNKs have been implicated in cell death through inhibition of the JNK pathways. SR 3306 can potentially protect the brain against cell death that is characteristic of Parkinson's and other neurodegenerative disorders.   
 
Lead researcher Dr. Philip LoGrasso, a professor in the Department of Molecular Therapeutics and senior director of drug discovery at Scripps' Jupiter, Fla., campus, has been studying the effects of SR 3306 for several years and recently published his findings in the American Chemical Society journal Chemical Neuroscience. His results show that small doses of the drug produced a marked increase in neuron survival in cell cultures and animal models.   
 
"It was a surprise that that level of neuroprotection reduced the behavioral impact so strongly," LoGrasso says, "but it's indicative of how it might perform in human patients. While SR-3306 doesn't represent a cure, it does appear to have the potential of stopping the progression of the disease."  
 
Increasing the drug's market potential is its ability to be administered orally, as well as the success it has had in preventing neuron death in a rat model that mimics the physical symptoms of Parkinson's disease.  
 
"These studies present compelling data on the first oral, brain-penetrating inhibitor to show significant efficacy in preventing neurodegeneration in both mouse and rat models of Parkinson's disease," says LoGrasso.   
 
Executives at OPKO are equally enthusiastic about the potential SR 3306 has as a therapeutic for Parkinson's.   
 
"We are excited to be working with Dr. LoGrasso and the Scripps Research Institute to develop this important compound which could prevent the progression of Parkinson's disease, and not just treat the symptoms of the disease," says Dr. Phillip Frost, chairman and CEO of OPKO.
 
There are currently no other drugs on the market that target the cause of Parkinson's disease, Frost notes. Current treatments such as levodopa and MAO-B inhibitors are aimed at controlling symptoms. These drugs work by creating more dopamine in the brain to compensate for the loss of dopaminergic neurons, thus reducing symptoms, but their effects only extend so far.
 
"A drug like SR-3306 that prevents neurodegeneration would be a quantum leap in the clinical treatment of Parkinson's disease because all current therapies treat only the symptoms of the disease, not the underlying pathologies," adds LoGrasso.  
 
Though development of SR 3306 at OPKO is just beginning, the discovery presents a promising avenue for treating Parkinson's disease, a condition that, according to the Parkinson's Disease Foundation, affects more than 60,000 Americans and as many as 10 million people worldwide. According to LoGrasso, "This licensing agreement will help ensure that the development of this promising compound keeps moving forward. This is one of the best opportunities we have for the development of an effective neuroprotective treatment for Parkinson's patients."  
 
Financial details of the agreement were not disclosed.
 
Code: E041223

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