Seyfried T.N.,Boston College |
Shelton L.M.,Minerva Biotechnologies |
Huysentruyt L.C.,University of California at San Francisco
Neuromethods | Year: 2013
Information is presented on the new VM-M3 mouse model for glioblastoma multiforme (GBM). The VM-M3 tumor arose in the brain of inbred VM strain, which is known to have a high incidence of spontaneous brain tumors. The failure to develop effective treatments for GBM has been due in part to the failure of animal models to manifest the key invasive properties of the disease. Scherer originally described the properties of malignant brain tumors in terms of their invasive behavior independent of cell classification. These properties are referred to as Secondary Structures and involve growth and invasion along blood vessels, through ventricles, white matter tracts, through the corpus callosum and across pial membranes. While extracranial metastasis is not often reported, numerous reports show that GBM can be highly metastatic if the cells gain access to extracranial sites. The VM-M3 GBM model is unique in displaying the Secondary Structures of Scherer and showing systemic metastasis when grown outside the CNS. The VM-M3 cells express the luciferase gene and can be used to assess quantitatively distal CNS invasion. Evidence is presented showing the calorie restriction reduces VM-M3 CNS invasion. The VM-M3 model will be useful for evaluating new therapies for GBM. © 2013 Springer Science+Business Media New York.
Seyfried T.N.,Boston College |
Marsh J.,Boston College |
Marsh J.,Yeshiva University |
Shelton L.M.,Boston College |
And 4 more authors.
Epilepsy Research | Year: 2012
Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer. © 2011 Elsevier B.V.
PubMed | University of New Brunswick, Minerva Biotechnologies and University of Maine, United States
Type: | Journal: Skeletal muscle | Year: 2016
Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition.We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture.These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.
Smagghe B.J.,Minerva Biotechnologies |
Stewart A.K.,Minerva Biotechnologies |
Carter M.G.,Minerva Biotechnologies |
Shelton L.M.,Minerva Biotechnologies |
And 9 more authors.
PLoS ONE | Year: 2013
We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more "naïve" state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell's inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell's exit from pluripotency. © 2013 Smagghe et al.
Thompson A.B.,Minerva Biotechnologies |
Calhoun A.K.,Minerva Biotechnologies |
Smagghe B.J.,Minerva Biotechnologies |
Stevens M.D.,Minerva Biotechnologies |
And 4 more authors.
ACS Applied Materials and Interfaces | Year: 2011
Gold nanoparticles hold great promise for studying protein-protein interactions because of their intrinsic optical properties. Pink when in a homogeneous suspension, the solution turns blue-gray when particles are drawn close together, for example, when immobilized proteins specifically interact with each other. However, the nanoparticle stability, size, and method of protein attachment contribute to the unreliable outcome of current assays. To overcome these hurdles, we developed novel and reliable methods first to synthesize homogenous particles of optimal diameter and second to apply a heterologous NTA-Ni-SAM coating for controlled orientation and optimal presentation of histidine-tagged proteins. Both methods were proven to greatly enhance assay sensitivity and specificity by increasing the signal and minimizing the nonspecific binding. Our assay reproducibly detected known protein-protein interactions and unambiguously identified small molecules that inhibited them. We believe our gold nanoparticle bioassay is a versatile and trustworthy new platform for analyzing protein-protein interactions and high-throughput screening of small-molecule inhibitors. © 2011 American Chemical Society.
PubMed | Minerva Biotechnologies
Type: Journal Article | Journal: Stem cells (Dayton, Ohio) | Year: 2016
Scientists have generated human stem cells that in some respects mimic mouse nave cells, but their dependence on the addition of several extrinsic agents, and their propensity to develop abnormal karyotype calls into question their resemblance to a naturally occurring nave state in humans. Here, we report that a recombinant, truncated human NME7, referred to as NME7AB here, induces a stable nave-like state in human embryonic stem cells and induced pluripotent stem cells without the use of inhibitors, transgenes, leukemia inhibitory factor (LIF), fibroblast growth factor 2 (FGF2), feeder cells, or their conditioned media. Evidence of a nave state includes reactivation of the second X chromosome in female source cells, increased expression of nave markers and decreased expression of primed state markers, ability to be clonally expanded and increased differentiation potential. RNA-seq analysis shows vast differences between the parent FGF2 grown, primed state cells, and NME7AB converted cells, but similarities to altered gene expression patterns reported by others generating nave-like stem cells via the use of biochemical inhibitors. Experiments presented here, in combination with our previous work, suggest a mechanistic model of how human stem cells regulate self-replication: an early nave state driven by NME7, which cannot itself limit self-replication and a later nave state regulated by NME1, which limits self-replication when its multimerization state shifts from the active dimer to the inactive hexamer.
News Article | August 4, 2015
WALTHAM, Mass. & KYOTO, Japan--(BUSINESS WIRE)--Minerva Biotechnologies and iPS Academia Japan, Inc. announced today that they have signed an agreement granting Minerva worldwide rights to use and commercialize the induced Pluripotent Stem (iPS) cells patent portfolio arising from the work of Professor Shinya Yamanaka, MD, Ph.D., who won the Nobel Prize for Medicine in 2012 for his discovery of four genes that can reprogram an adult’s cell to go back in time to become that person’s own stem cell. Minerva Biotechnologies discovered a naturally occurring, primitive growth factor that continues this reprogramming to an even earlier, embryonic-like point called the ‘naïve’ state. Scientists believe that because these earlier, naïve stem cells have a clean slate, they are more easily directed to develop into functional mature cells, which could be used for transplant. Naïve stem cells have several advantages over currently available stem cells (known as ‘primed’ state). These advantages are important for the future of stem cell therapies. Naïve stem cells do not yet have DNA methylation marks that commit the cells to certain developmental decisions. Additionally, naïve stem cells have a much higher cloning efficiency than primed state cells, which is critical for the realization of stem cell based gene therapies. Importantly, only naïve stem cells can contribute to the generation of chimeric animals. A futuristic stem cell therapy, which may not be that far off, is the generation of human-non-human chimeras that would express some human tissues or even entire human organs, for transplant. Minerva’s proprietary primitive stem cell growth factor dramatically increases the efficiency of making human iPS cells, which greatly reduces the time and the cost of making iPS cells for research or for personalized stem cell banking. A problem that currently plagues the stem cell field is that although protocols have been devised that direct stem cells to mature into specific cell types, not every iPS cell line can mature into any cell type. As a consequence, researchers have to test many stem cell clones to determine which ones can form heart cells, which ones can form liver cells, etc. This problem is called ‘clonal restriction’ and would make personalized stem cell therapy impractical. In contrast, human iPS cells generated with Minerva’s technology are not clonally restricted; each of our human iPS cell clones has been demonstrated to have the ability to mature into heart cells, liver cells or neural cells. Minerva’s naïve state human iPS cells, or mature cells generated from, can be rapidly and inexpensively generated for use in basic research, drug toxicity testing or for personalized stem cell banking. The agreement with iPS Academia Japan allows Minerva to generate and sell naïve state human iPS cells as well as mature cells derived from them, for research, drug toxicity testing and for personalized stem cell banking. Minerva Biotechnologies is the first company to generate human naïve state iPS cells using a single, naturally occurring human stem cell growth factor. Previous attempts to grow human stem cells in the elusive naïve state, which used cocktails of biochemical inhibitors and mouse growth factors, were prone to develop abnormal karyotype. Naïve stem cells generated with Minerva’s primitive growth factor have normal and stable karyotype. The generation of iPS cells from adult skin or blood cells does not involve the use of embryos and so does not invoke ethical issues. “The agreement with iPS Academia Japan provides Minerva with a powerful combination of technologies that will advance the study of basic science as well as accelerate the timeline to clinical applications of regenerative medicine,” said Dr. Cynthia Bamdad, CEO Minerva Biotechnologies. “We are very excited about our relationship with iPS Academia Japan that allows us to disseminate our technology to others.” “iPS Academia Japan is pleased to grant a non-exclusive license to Minerva Biotechnologies. Distribution of iPS cell products or provision of services are important for development of iPS cell research and its practical application,” said Mitsuomi Shirahashi, president and CEO of iPS Academia Japan, Inc. “We believe that this collaboration can contribute to the significant step toward bright future of iPS cell technology.” Minerva Biotechnologies is a pioneer in the field of stem cells and cancer stem cells. Minerva was first to discover that cancer cells hijack an otherwise normal stem cell growth mechanism, involving a growth factor receptor called MUC1* (pronounced muk 1 star). By studying human stem cells in parallel with human cancer cells, Minerva scientists figured out how cancer cells override the normal ‘shut off’ switch that stops stem cells from self-replicating indefinitely. The Company is developing a panel of anti-cancer drugs that target a cancer-specific MUC1* growth factor receptor and a testis specific cancer antigen that promotes metastasis. As of this date, Minerva will market its naïve state stem cells and its naïve-inducing stem cell growth factor and reagents. For more information, visit www.minervabio.com iPS Academia Japan, Inc. (AJ) is an affiliate of Kyoto University, and its main role is to manage and utilize the patents and other intellectual properties held/controlled by Kyoto University and other institutions in the field of iPS cell technologies so that the research results contribute to health and welfare worldwide. AJ was established in Kyoto in June 2008. AJ’s patent portfolio consists of about 110 patent families (the total number of patent applications is about 350 cases) in the iPS cell technologies as of July 2015, and about 150 license arrangements have been executed with domestic or international entities. For more information, visit www.ips-cell.net.
News Article | February 15, 2017
WALTHAM, Mass.--(BUSINESS WIRE)--Minerva Biotechnologies, a leading cancer therapy and regenerative medicine company, today announced the launch of the AlphaSTEM™ Culture System. The system uses a newly discovered growth factor that is only expressed in the naïve cells of the inner cell mass during the earliest days of embryogenesis. AlphaSTEM™ Culture System is a simple, natural method for inducing the naïve state in human stem cells without the use of biochemical inhibitors. Naïve stem cells do not yet have DNA methylation marks that have already committed the cells to certain developmental decisions. Directed differentiation efficiency and functionality are increased with ‘clean slate’ AlphaSTEM™ naïve cells. Stem cells cultured in AlphaSTEM™ maintain normal karyotype for 70 passages. Stem cell expansion is faster and scalable, and can be completely automated since it eliminates unwanted spontaneous differentiation. Further, iPSC generation in AlphaSTEM™ Culture System is orders of magnitude more efficient than FGF-based reprogramming. “Our products will advance stem cell based disease research as well as accelerate the timeline to clinical applications of regenerative medicine,” said Dr. Cynthia Bamdad, CEO of Minerva Biotechnologies. “Minerva’s stem cell technology solves the manufacturing, safety and quality issues that have impeded the development of regenerative therapies.” The AlphaSTEM™ Culture System includes the following products: For more information on ordering AlphaSTEM™, please visit: www.minervabio.com. About Minerva Biotechnologies Minerva Biotechnologies is developing therapies for curing cancers and commercializing core technology that will enable next generation stem cell therapies. Minerva is the first company to generate human naïve state pluripotent stem cells using a single, naturally occurring human stem cell growth factor. Carter, M.G., Smagghe, B.J., Stewart, A.K., Rapley, J.A., Lynch, E., Bernier, K.J., Keating, K.W., Hatziioannou, V.M., Hartman, E.J. and Bamdad, C. C. (2016), A Primitive Growth Factor, NME7AB, Is Sufficient to Induce Stable Naïve State Human Pluripotency; Reprogramming in This Novel Growth Factor Confers Superior Differentiation. Stem Cells, 34: 847–859. doi:10.1002/stem.2261
News Article | February 28, 2017
ATLANTA, GA--(Marketwired - Feb 28, 2017) - True Nature Holding, Inc. ( : TNTY) (the "Company") announced that it has appointed Mr. James C. Czirr to its Board of Directors, effective immediately. Mr. Czirr, age 63, is a seasoned public company executive with experience in both early stage and established companies. He lends his vast business and pharmaceutical expertise to the Board of Directors, fortifying the Company's ability to build shareholder value through the consolidation of compounding pharmacy businesses. Of note, Czirr is the managing member of an investment fund focused on the strategic financing of emerging pharmaceutical businesses. With the addition of Mr. Czirr, True Nature's Board of Directors has grown to four members. "Jim brings a depth of public company experience as well as a targeted pharmaceutical industry perspective, and we will undoubtedly benefit from his ability to skillfully represent the Company to the public and to investors," said Amy Lance, Chairman of the Board of Directors. Mr. Czirr stated; "I believe the True Nature Holding strategy is well-timed and represents a rapid growth opportunity in a marketplace shifting toward consolidation." He continued, "The acquisition and roll-up of compounding pharmaceutical operations per the Company's business model makes sense economically in a time of price sensitivity to the rising costs of drug development, distribution and regulation." Mr. James C. Czirr, also known as "Jim," served as the Chief Executive Officer of Minerva Biotechnologies Corp. Mr. Czirr served as the President of Extol Energy Corporation, a syndicator of oil and gas wells from 1982 to 1988. He served as both a member of the board and Executive Vice President of Business Development at Pro Pharmaceuticals Inc. (AKA Galectin Therapeutics, Inc.) from June 2000 to November 2003. He was an Independent Corporate and Public Relations Consultant for over ten years, working with various companies regarding business strategies, including issues such as organization of production, finance and capital programs, marketing strategies and incentive programs. In 2009, Mr. Czirr organized the 10X Fund LP to provide turnaround financing for Pro-Pharmaceuticals. He served as the Executive Chairman of Galectin Therapeutics, Inc. from February 11, 2010 to January 8, 2016, and as the Chairman of Galectin Therapeutics from February 12, 2009 to February 11, 2010. He continues to serve as a Director of Galectin Therapeutics, Inc. He served as a Director of NACO Industries, Inc. Between 1997 and 2000. Mr. Czirr received a B.B.A. degree from the University of Michigan in 1976 and has completed post-graduate courses at the University of Toledo School of Business Administration, and at the College for Financial Planning from which he received the CFP designation. The Mission of True Nature Holdings, Inc. To unlock the potential of the compounding pharmacy industry to improve human and animal health, serve unmet patient needs, elevate the dignity of skilled pharmacists, and build shareholder value through the delivery of quality, cost effective, and innovative healthcare products and pharmaceuticals to the world. The Vision of True Nature Holdings, Inc. To become globally recognized for our best practices focused on driving quality, efficiency, and sustainability in the compounding pharmaceutical industry, natural solutions for healthy living, and novel approaches for delivery of these solutions. Statement Under the Private Securities Litigation Reform Act As contemplated by the provisions of the Safe Harbor section of the Private Securities Litigation Reform Act of 1995, this news release contains forward-looking statements pertaining to future, anticipated, or projected plans, performances, and developments, as well as other statements relating to future operations. All such forward-looking statements are necessarily only estimates or predictions of future results or events and there can be no assurance that actual results or events will not materially differ from expectations. Further information on potential factors that could affect True Nature Holding, Inc. is included in the Company's filings with the Securities and Exchange Commission. We expressly disclaim any intent or obligation to update any forward-looking statements. To learn more about the Company, visit www.truenaturepharma.com. A one-page investor information document can be viewed at the following link: http://truenaturepharma.com/wp-content/uploads/2017/02/tnty-investor-info-sheet.20170227.pdf