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
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
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
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.
For further information please contact: Tami Horovitz Tel: +972-8-9385100 Fax: +972-8-9300795 Email: email@example.com
SOURCE D-Pharm Ltd