SAN FRANCISCO and GENEVA, July 18, 2014 (GLOBE NEWSWIRE) -- Amarantus Bioscience Holdings, Inc. (OTCQB:AMBS), a biotechnology company focused on the discovery and development of novel diagnostics and therapeutics related to endoplasmic reticulum stress, cell cycle dysregulation, neurodegeneration and apoptosis, today announced that it has updated its MANF publications list with 8 previously undisclosed independent peer-reviewed research papers. The scientific articles include several Chinese publications as well as new publications that have been released since the beginning of 2014.
"The continual increase in publications on MANF speaks to the uniqueness of MANF's activity and its ability to rescue cells across a spectrum of protein misfolding-related disorders," commented David A. Lowe, PhD, member of the Amarantus Board of Directors. "MANF is emerging as an especially interesting scientific target, thereby increasing the value of the Company's intellectual property and expanding its therapeutic potential immensely."
Parkinson's disease: Building and expanding from a strong basis of MANF literature in Parkinson's disease, diabetes, Alzheimer's disease and Retinitis Pigmentosa, recent literature has further strengthened the rational in Parkinson's disease (1) with an independent confirmation of MANF's activity in the 6-OHDA model. MANF's therapeutic effects have now been demonstrated by three independent research groups across Europe, the United States and China. Moreover, the involvement of MANF in the central nervous system development (2) provides clues to further our understanding of MANF's demonstrated regenerative activity in PD models.
New indications: MANF's neuroprotective activity was confirmed in a model of stroke, together with a deeper understanding of its anti-apoptotic mechanism of action involving the unfolded protein response (3). A further expansion into the orphan space was enabled by MANF's rescue activity in a genetic model of spinal cerebellar ataxia 17 (4).
Mechanism-of- action: Academic research groups are increasingly picking up research on MANF and advance our understanding of its mechanism of action with important implications to clinical development. Previously known effects of MANF on apoptosis are understood at increasing level of detail (5) and MANF signaling is started to being elucidated by demonstration of MANF-induced activation of PKC signaling (4). Finally, protein engineering studies continue to advance our understanding of the essential elements of MANF's protein structure for its function (6).
Small molecule screens: Building on the body of work generated with MANF as a therapeutic protein the expansion into small molecule mimetics of MANF activity offers important new opportunities, addressing MANF intracellular effects in response to cellular stress. Tools are continuously being developed to enable small molecule screens. Increasing the understanding of MANF promoter function (7) and the example of a novel screening assay to detect secreted MANF (8) will advance the search for MANF small molecule mimetics.
1.) Wang Y. et al. (2012) Alleviation of neuronal damage by MANF in rat model of Parkinson's disease. Acta Universitatis Medicinalis Anhui 47(7).
2.) Wang H. et al. (2014) Spatiotemporal Expression of MANF in the Developing Rat Brain. PLoS One 9(2):e90433.
3.) Yang W. et al. (2014) Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis. J Neurol Sci.
4.) Yang S et al. (2014) Age-Dependent Decrease in Chaperone Activity Impairs MANF Expression, Leading to Purkinje Cell Degeneration in Inducible SCA17 Mice. Neuron 81: 349-365.
5.) Chen et al. (2013) Protective effect of MANF on endoplasmic reticulum stress-induced apoptosis. Acta Universitatis Medicinalis Anhui 48(11):1308.
6.) Lindstrom R et al. (2013) Characterization of the Structural and Functional Determinants of MANF/CDNF in Drosophila In Vivo Model. PLoS One 8: e73928.
7.) Li Zhang, Peng Lu, Tao Wang, Yuxian Shen (2012) Cloning and activity analysis of the promoter of MANF gene. Chinese Pharmacological Bulletin 28(6).
8.) Norisada J, Hirata Y, Amaya F, Kiuchi K, Oh-Hashi K (2014) A sensitive assay for the biosynthesis and secretion of MANF using NanoLuc activity. Biochem Biophys Res Commun 449(4):483-489.
About Mesencephalic-Astrocyte-derived Neurotrophic Factor (MANF)
MANF (Mesencephalic-Astrocyte-derived Neurotrophic Factor) is believed to have broad potential because it is a naturally-occurring protein produced by the body for the purpose of reducing and preventing apoptosis (cell death) in response to injury or disease, via the unfolded protein response of the endoplasmic reticulum. By manufacturing MANF and administering it to the body, Amarantus is seeking to use a regenerative medicine approach to assist the body with higher quantities of MANF when needed. Amarantus is the front-runner and primary holder of intellectual property (IP) around MANF, and is initially focusing on the development of MANF-based protein therapeutics. MANF's current lead indication is Retinitis Pigmentosa, and other applications including Parkinson's disease, Alzheimer's disease and Wolfram's Syndrome. Additional applications for MANF may include Traumatic Brain Injury (TBI), myocardial infarction, antibiotic-induced ototoxicity and certain other rare orphan diseases currently under evaluation.
About Amarantus BioScience Holdings, Inc.
Amarantus BioScience Holdings (AMBS) is a biotechnology company developing treatments and diagnostics for diseases associated with neurodegeneration and protein misfolding-related apoptosis. AMBS has licensed Eltoprazine ("Eltoprazine"), a phase 2b ready small molecule indicated for Parkinson's Levodopa induced dyskinesia and Adult ADHD. AMBS has an exclusive worldwide license to the Lymphocyte Proliferation test ("LymPro Test(R)") for Alzheimer's disease and owns the intellectual property rights to a therapeutic protein known as Mesencephalic-Astrocyte-derived Neurotrophic Factor ("MANF") and is developing MANF-based products as treatments for brain disorders. AMBS also owns intellectual property for the diagnosis of Parkinson's disease ("NuroPro") and the discovery of neurotrophic factors ("PhenoGuard"). Amarantus operations are located at Janssen Labs @QB3 in San Francisco, CA. For further information please visit www.Amarantus.com, or connect with the Company on Facebook, LinkedIn, Twitter and Google+.
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