Plasticise Brings Plasticity - Promoting Treatments Closer to the Clinic
Plasticise is coordinated by Prof. James Fawcett from the University of Cambridge (UK) and brings together leading scientists, clinicians, small biotechs and large pharmaceutical companies from 8 different European countries. Neurodegenerative diseases are the major causes of chronic disability in European communities. The academic and clinical research work of Plasticise teams is targeting Alzheimer’s disease, Stroke, Traumatic Brain Injury and Spinal Cord Injury. Some of the latest Plasticise highlights are presented below. PLASTICISE 2nd ANNUAL MEETING, STRESA, ITALY The network gathered in Stresa (Italy) in May 2011 for its 2nd annual meeting. An impressive number of new advances, mainly in the field of animal and theoretical modeling and of combination of treatment approaches, were presented at the meeting. Those include the development by collaborative teams of new animal models for Alzheimer disease and stroke; the promising new assessments of plasticity in stroke patients upon rehabilitation, and the combination of treatment approaches (Nogo-A, chondroitinase, rehabilitation,…). It is expected that some of these promising results will now lead to breakthroughs in several areas of plasticity, and will have a significant resonance in clinical research. HOW SYNAPSE PLASTICITY CONTRIBUTES TO MEMORY FORMATION AND RECALL The team of Pico Caroni, one of Plasticise’s partners, has recently provided evidence that learning specifically produces a rise in the number of synapses that trigger feedforward inhibition, which is crucial for memory precision. An article has been recently published in Nature (http://www.ncbi.nlm.nih.gov/pubmed/21532590(opens in new window)). Using green fluorescent protein-labelled large mossy fibre terminals (LMTs) mouse, the authors found a significant, long-lasting and reversible increase in the number of filopodial synapses and putative presynaptic sites in hippocampus following a hippocampus-dependent task (contextual fear conditioning or spatial learning in the Morris water maze). Moreover, memory recall following contextual fear conditioning was also associated with strong c-FOS signals in CA3b pyramidal neurons, highlighting the specificity of this learning-related feedforward inhibition. These findings were further confirmed by experiments performed with use of knockout mice models (Rab3a-/-, lacking long-term potentiation (LTP) at mossy fibres and adducin 2 (Add2-/-) which exhibit early LTP but are unable to stabilize new synapses). Interestingly, similar structural rearrangements and feedforward inhibitory connectivity were observed in the cerebellum following tasks that involve cerebellar circuits (cued fear conditioning and the rotarod test). In conclusion, the authors suggest the existence of the link between learning-related increases in the numbers of defined synapses and the precision of learning and memory in the adult. Their findings put new light on the functional role of structural plasticity in learning and memory, and contribute to our understanding of learning disabilities and memory impairments. D.PHARM BRINGS DP-B99, A NEUROPROTECTIVE DRUG FOR ISCHEMIC STROKE , TO PHASE III. D-Pharm, a member of the Plasticise research network, has presented during the 2nd consortium annual meeting, the progress of the ongoing clinical trial for their compound DP-b99. D-Pharm (www.dpharm.com) is a clinical stage, biopharmaceutical company pioneering the development of lipid-like therapeutics established in 1993 at the initiative of Dr. Alex Kozak The company has generated a rich pipeline of patent protected proprietary products which includes advanced clinical stage products. DP-b99 is a unique broad-spectrum neuroprotective drug that addresses an array of brain damaging processes occurring in stroke patients. Both preclinical and clinical Phase I and II studies indicate a favorable efficacy and safety profile for DP-b99. In the Phase IIb trial in 150 ischemic stroke patients, DP-b99 increased by two-fold the percentage of patients that recovered from ischemic stroke. The protocol for its ongoing, Phase III, Membrane Activated Chelator Stroke Intervention (MACSI) study has been recently presented in the International Journal of Stroke (http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2011.00608.x/abstract(opens in new window)). The primary objective MACSI is to evaluate the safety and therapeutic effects of intravenous 1.0mg/kg/day DP-b99, initiated within nine-hours of stroke onset in patients with moderately severe hemispheric acute ischemic stroke. The protocol was agreed with the U.S. FDA and the DP-b99 development program has been granted Fast Track status by the U.S. FDA. As pointed by Dr. Gilad Rosenberg, D-Pharm’s V.P. of Clinical Development: “DP-b99 is the most advanced industry-developed neuroprotective agent in clinical development”. The MACSI study is enrolling 770 patients, with recruitment in over 100 clinical sites in North America, Europe, South America, South Africa and Israel.
Countries
Germany, France, Italy, Netherlands, Poland, United Kingdom