D-Pharm's DP-b99 Prevents Abnormal Neuronal Plasticity and Pathological Brain Reorganization
REHOVOT, Israel, June 12, 2014 /PRNewswire/ --
D-Pharm Ltd. (TASE: DPRM) announced today, publication in PLOS ONE, of promising results from a study of its drug candidate DP-b99. The findings suggest that DP-b99 may prevent lasting alterations in neuronal function and pathological brain reorganization - a hallmark of numerous central nervous system (CNS) diseases. The data demonstrate the potential of D-Pharm's drug candidates derived from D-Pharm's platform technology (MACs) to modify the course of epilepsy, as well as possibly other neurodegenerative diseases linked to aberrant neuronal plasticity.
The brain has an ability to reorganize itself by forming new neural connections throughout life. Many CNS diseases alter this critical process and are both initiated and supported by aberrant neuronal plasticity and abnormal brain "wiring". Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent protease that is released in response to enhanced neuronal activity or various brain tissue injuries, and contributes to synaptic plasticity, both harmful and beneficial. In the present study, (for link to the publication see http://dx.plos.org/10.1371/journal.pone.0099789) DP-b99, was shown inhibit MMP-9 activity and impede various MMP-9-dependent adverse effects.
In brief, DP-b99 treatment reduced proteolysis of an MMP-9 substrate, both in vitro and in vivo. DP-b99 was neuroprotective against kainate induced neuronal loss and prevented MMP-9-mediated dendritic spine transformation. The drug induced significant delay in the development of chemically-induced seizures, with aberrant mossy fiber sprouting diminished by DP-b99. DP-b99 thus affects important hallmarks of epileptogenesis, such as neuronal cell loss and aberrant synaptic plasticity of remaining cells. Previously, DP-b99 has been shown to reduce MMP-9's activity in an in vivo stroke model, a reduction that correlated with improved neurological outcome and smaller infarct volume (International Journal of Stroke 2010, 5 (Suppl. 2), 15).
This study was performed at the Nencki Institute of Experimental Biology in Warsaw, Poland, in the laboratory of Prof. Leszek Kaczmarek. Our collaboration with Prof. Kaczmarek's group originated as part of the 'Plasticise' European Framework FP7 funded consortium.
DP-b99, D-Pharm's most advanced drug candidate, emerged from D-Pharm's platform technology, Membrane Active Chelators (MAC). DP-b99 reached Phase 3 clinical testing in stroke patients. Currently, D-Pharm is carrying out a Phase 2 study of DP-b99 in acute pancreatitis patients.
About MAC technology
Disrupted metal ion homeostasis is symptomatic of numerous diseases, ranging from inflammation, cardiac arrhythmia, myocardial infarction and acute stroke to chronic neuro-degeneration (e.g. Alzheimer's and Parkinson's diseases). D-Pharm's breakthrough was to recognize metal ion distribution within cell membranes as a distinct, novel target for therapeutic intervention. D-Pharm's MAC technology enables rational design of lipophilic drugs to modulate the distribution of metal ions such as copper, zinc, calcium and iron selectively within cell membranes and membrane milieus, rendering their action localized and safe.
D-Pharm (http://www.dpharm.com) is a clinical stage, technology-driven biopharmaceutical company developing proprietary products for treatment of CNS disorders. D-Pharm's pipeline includes three clinical stage 2 products, as well as a rich preclinical development pipeline for Alzheimer's disease, and other types of dementia.
Statements in this press release that are not historical facts are forward-looking information, as defined in the Securities Law, based on information available to D-Pharm at the time of this press release. The estimations could, some or all, be unrealized, or could be realized in significantly different ways than expected.
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SOURCE D-Pharm Ltd