Day 1 :
Keynote Forum
Gjumrakch Aliev
GALLY International Biomedical Research Consulting LLC., USA
Keynote: Conjugates of γ-carbolines and phenothiazine as new multitarget inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer disease
Biography:
Gjumrakch Aliev authored and coauthored more than 500 publications in the fields of neurodegenerative diseases research (Alzheimer disease), as well as cardio- and cerebrovascular disease, cancer, and electron microscopy. He is an outstanding teacher, scholar, and a renowned scientist in the area of cellular molecular physiology, and cardiovascular, and neurodegeneration-mediated pathologies including Alzheimer disease (AD). He is nationally and internationally reputed in his area. Dr. Aliev’s accomplishments in the area of biochemistry and cellular biology have tremendous implications for drug design towards CNS Neurological Disorders, AD, cancer, and cerebrovascular and neurodegeneration related pathologies. He is world-renowned expert in electron microscopy. His work has been published in numerous prestigious journals such as Nature Clinical Cardiology, J. Neuroscience, Scientific Reports, Circulation Research, New England journal of Medicine, Blood, J. Cellular and Molecular Medicine, Atherosclerosis, CNS Neurological Disorders & Drug Targets, international J. Biochemistry and Cell Biology, and many others which reflect his leading role in his research areas. He is currently the Editor in Chiefs for “Central Nervous System Agents in Medicinal Chemistry”, “Applied Cell Biology”, “World Journal of Neuroscience”, “Open Journal of Psychiatry”, “Journal of Aging Science”, “Cardiovascular & Hematological Agents in Medicinal Chemistry”, “Immunology, Endocrine and Metabolic Agent in Medicinal Chemistry” as well as which by itself shows the voluminous and outstanding work he has accomplished in the area of cellular and molecular biology as well as aged associated clinical sciences. He is one of most cited authors in his fields with high impact factors.
Abstract:
The development of novel compounds that are able to modify the pathogenesis of neurodegenerative diseases appears to be as a promising approach among different drug discovery strategies in this emerging area. Taking into account the multifactorial nature of neurodegenerative diseases, focusing on the design of multitarget drugs that are capable to act simultaneously on different main biotargets, which are involved in the disease pathogenesis, seems to be very attractive and promising. During the past decade, previous studies have indicated that the progression of Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS) and some other neuropathological disorders is closely connected to dysfunctions in cholinergic and glutamatergic neuronal systems In addition, AD is a multifactorial pathology and the development of new multitarget neuroprotective drugs is promising and attractive. We synthesized a group of original compounds, which combine in one molecule γ-carboline fragment of dimebon and phenothiazine core of methylene blue (MB) linked by 1-oxo- and 2-hydroxypropylene spacers. Inhibitory activity of the conjugates toward acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and structurally close to them carboxylesterase (CaE), as well their binding to NMDA-receptors were evaluated in vitro and in silico. These newly synthesized compounds showed significantly higher inhibitory activity toward BChE with IC50 values in submicromolar and micromolar range and exhibited selective inhibitory action against BChE over AChE and CaE. Kinetic studies for the 9 most active compounds indicated that majority of them were mixed-type BChE inhibitors (Figure 1). The main specific protein-ligand interaction is π-π stacking of phenothiazine ring with indole group of Trp82. These compounds emerge as promising safe multi-target ligands for the further development of a therapeutic approach against aging-related neurodegenerative disorders such as Alzheimer and/or other relevant pathological conditions.
Keynote Forum
Esmaiel Jabbari
University of South Carolina, USA
Keynote: Nanomaterials in regenerative medicine and cancer therapy
Time : 11:00-11:30
Biography:
Esmaiel Jabbari is Tenured Full Professor of Chemical and Biomedical Engineering at the University of South Carolina. He directs the biomaterials, tissue engineering, and drug delivery laboratory which specialize on the design of 3D multi-cellular co-culture systems to study the effect of nanoscale spatiotemporal delivery of morphogens and physico-mechanical factors on the fate of stem cells. He has received numerous awards for his research program including the Berton Rahn Award in 2012 from the AO Foundation, the Stephen Milam Award in 2008 from the Oral and Maxillofacial Surgery Foundation, and elected for the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE) in 2013. He is the author of more than 250 books, book chapters, refereed journal articles and conference proceedings and he has mentored more than 130 scholars. He has served as the Academic Editor for PLOS ONE.
Abstract:
Nanomedicine is poised to shape the sustainability of industries and wealth of nations, and transform economies and societies on a global scale. The global market for nanomedicine was $250 billion in 2014 and it is expected to reach $550 billion by 2020. Nanotechnology is the solution to detection, diagnosis, and treatment of many diseases as biological processes and cellular mechanisms work at the nanoscale. Translation of nanoscale discoveries from the laboratory to the market promises new diagnostic tools, drug targeting systems, gene therapy platforms, biomaterials, regenerative tissue constructs, and personalized medicine. A major application of nanotechnology in medicine is in cancer therapy. A major contributing factor to mortality in cancer patients is relapse after therapy and developing resistance. Cancer recurrence and resistance is related to the existence of a very small population of initiating stem cells in the tumor tissue. The author will present strategies based on nanomaterials to selectively target chemotherapeutic agents to the stem cell sub-population of cells in the tumor tissue. Another important application of nanomedicine is in regeneration of skeletal tissues. In the process of bone formation, osteogenesis and vascularization are coupled by spatiotemporal regulation of paracrine signaling in which the invading vascular endothelial cells secrete osteogenic morphogens to stimulate cell differentiation and bone formation. The stratified structure of articular cartilage is rooted in the spatiotemporal gradients of morphogens that direct the formation of morphologically distinct cartilage zones. The author will present nanoparticle-based strategies for spatiotemporal release of morphogens for coupling osteogenesis and vascularization and to stimulate the formation of zonal architecture of articular cartilage
Keynote Forum
Robert J Lee
The Ohio State University, USA
Keynote: Lipid nanoparticles for delivery of therapeutic oligonucleotides
Biography:
Robert J Lee has received his PhD in 1994 from Purdue University. He was trained as a Postdoc at the University of Pittsburgh School of Medicine and worked at GeneMedicine Inc. as a Sr. Scientist and then at Endocyte Inc. as VP of R&D. He has been a Professor in the College of Pharmacy at The Ohio State University since 1997 and has more than 200 publications in the areas of targeted drug delivery systems and lipid-based nanoparticles. He has served regularly on NIH review panels and as the PI or Co-PI on many large NIH and NSF projects. He has collaborated extensively with biotech industry in his research on oligonucleotide delivery systems.
Abstract:
Oligonucleotides, including antisense oligos, siRNA, miRNA mimics, anti-miRs, are promising as therapeutic agents because of their ability to regulate expression of specific or networks of genes that are critical in human diseases. However, clinical translation of oligonucleotide therapeutics has had limited success partly due to their limited nuclease stability and obstacles in their in vivo delivery, especially to tissues other than the liver. To address these issues, a combination of chemical modifications and lipid nanoparticle (LNP)-based delivery strategy has been developed. Design of LNPs needs to balance the requirements of stability in circulation and ability to facilitate intracellular delivery. Additional consideration is needed to address hematological biocompatibility and effects on the immune system. Specific examples will be provided on several novel LNP formulations for therapeutic delivery of miR-29b mimics, anti-miR21, and antisense oligos to Akt-1 in murine tumor models.
Keynote Forum
Stephan T Stern
Nanotechnology Characterization Lab, USA
Keynote: Challenges in evaluation of nanomedicine pharmacokinetics and generic bioequivalence
Biography:
Stephan T Stern is Acting Deputy Director and Senior Principal Scientist at the National Cancer Institute’s Nanotechnology Characterization Laboratory (NCL), located at the Frederick National Laboratory for Cancer Research in Frederick, Maryland. The NCL assists in all phases of the nanomedicine drug development process, from early preclinical to late stage clinical trials, working with academic laboratories and the pharmaceutical industry. At the NCL, he oversees nanomedicine pharmacology and toxicology. Data generated from these studies support formulation optimization, regulatory filings, and environmental risk assessment. His research interests include novel drug formulation, bioanalytical method development, and pharmacokinetic modeling. Prior experience includes a postdoctoral fellowship at the University of North Carolina - Chapel Hill in the division of drug delivery and disposition, and curriculum in toxicology, and work within regulated areas of the pharmaceutical industry. He received his BS degree in biochemistry from the University of Rochester and his PhD in toxicology from the University of Connecticut at Storrs. He is a Diplomate of the American Board of Toxicology.
Abstract:
The success of nanomedicine (NM) drug delivery platforms relies upon their ability to influence drug disposition. Therefore, pharmacokinetic evaluation of NM is crucial to optimizing formulation properties and understanding how these properties result in therapeutic benefit. Comprehensive pharmacokinetic evaluation of NM requires quantification of several drug species, including NM encapsulated and encapsulated drug, and in some cases free and protein bound forms of the encapsulated drug as well. Indeed, the pharmacokinetic complexity of NM adds substantial difficulties to traditional pharmacokinetic and bioequivalence studies. This presentation will address the importance and challenges of monitoring the disposition and in vivo integrity of nanotechnology platforms, highlighting potential problems with current bioanalytical techniques, and introducing a new stable isotope tracer methodology currently under evaluation through a partnership between the FDA and NCI.