The California Institute for Regenerative Medicine was created in 2004 after 59% of California voters approved California Proposition 71 that governs the allocation of the $3 billion authorized to fund stem cell research in California. The agency was authorized to distribute the money in grants, funded by bonds, over a ten-year period to institutions and scientists throughout California that focused on advancing stem cell research and regenerative medicine. The mission of CIRM is: To support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease injury. Wikipedia.
News Article | May 12, 2017
Tim Henry, M.D., Director, Division of Cardiology in the Heart Institute at Cedars-Sinai Medical Center and Co-Principal Investigator of the ALLSTAR Trial, added, "We are encouraged to see reductions in left ventricular volume measures in the CAP-1002 treated patients, an important indicator of reverse remodeling of the heart. These findings support the biological activity of CAP-1002." Following Capricor's recent report of positive six-month data on clinical measures of skeletal muscle performance and cardiac biomarkers in the ongoing randomized 25-patient Phase I/II HOPE Trial of CAP-1002 in boys and young men with Duchenne muscular dystrophy (DMD), the Company plans to initiate enrollment into a randomized, double-blind, placebo-controlled, repeat-dose clinical trial of intravenous CAP-1002 in DMD in the second half of 2017, subject to regulatory approval. This anticipated trial will primarily evaluate skeletal (non-cardiac) muscle function. "The lack of a clear difference in the change in scar size from baseline to six months between the active and control groups in the interim observations from ALLSTAR was unexpected. These results diverge from the consistent and extensive record of activity observed with our cell technology in the setting of cardiac fibrosis as demonstrated by both preclinical and clinical studies, and we hope to gain an understanding of the factors that led to these observations through the conduct of further analyses," said Linda Marbán, president and CEO of Capricor. "Although we are disappointed, the favorable safety profile demonstrated by CAP-1002 in ALLSTAR supports the prospect of its chronic, repeat administration in patients with Duchenne muscular dystrophy. Also, the potent anti-inflammatory properties of CAP-1002 may be well-suited to mitigate DMD progression, for which chronic inflammation is believed to play a causative role," added Dr. Marbán. Capricor plans to reduce the scope of its operations, including the size of its workforce, in order to focus its financial resources primarily on its DMD program. Capricor management will hold a conference call at 5:00 a.m. PDT / 8:00 a.m. EDT today. The live call may be accessed by dialing (866) 868-1282 (domestic) or (847) 413-2405 (international) and by using the passcode 7330466. Access to the live webcast as well as the link to the replay of the call can be found at http://wsw.com/webcast/cc/capr2. The webcast will be archived for approximately 30 days. As previously announced, on May 15, 2017, Capricor will report its financial results for the first quarter of 2017. Capricor Therapeutics, Inc. (NASDAQ: CAPR) is a clinical-stage biotechnology company developing first-in-class biological therapies for cardiac and other medical conditions. Capricor's lead candidate, CAP-1002, is a cell-based candidate currently in clinical development for the treatment of Duchenne muscular dystrophy, myocardial infarction (heart attack), and heart failure. Capricor is also exploring the potential of CAP-2003, a cell-free, exosome-based candidate, to treat a variety of disorders. For more information, visit www.capricor.com. The ALLSTAR Trial is funded in part by the California Institute for Regenerative Medicine. Statements in this press release regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans regarding regulatory filings, future research and clinical trials; plans regarding current and future collaborative activities and the ownership of commercial rights; scope, duration, validity and enforceability of intellectual property rights; future royalty streams, expectations with respect to the expected use of proceeds from the recently completed offerings and the anticipated effects of the offerings, and any other statements about Capricor's management team's future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including statements containing the words "believes," "plans," "could," "anticipates," "expects," "estimates," "should," "target," "will," "would" and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements. More information about these and other risks that may impact Capricor's business is set forth in Capricor's Annual Report on Form 10-K for the year ended December 31, 2016, as filed with the Securities and Exchange Commission on March 16, 2017, and in its Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on September 28, 2015, together with prospectus supplements thereto. All forward-looking statements in this press release are based on information available to Capricor as of the date hereof, and Capricor assumes no obligation to update these forward-looking statements. CAP-1002 is an Investigational New Drug and is not approved for any indications. Capricor's exosomes technology, including CAP-2003, has not yet been approved for clinical investigation. For more information, please contact: To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/capricor-therapeutics-provides-update-on-allstar-trial-300456715.html
News Article | May 8, 2017
SHANGHAI, China and CUPERTINO, Calif., May 08, 2017 (GLOBE NEWSWIRE) -- Cellular Biomedicine Group Inc. (NASDAQ:CBMG) (“CBMG” or the “Company”), clinical-stage biopharmaceutical firm engaged in the development of effective immunotherapies for cancer and stem cell therapies for degenerative diseases, today reported financial results for the first quarter ended March 31, 2017 and provided business highlights. “The first quarter of 2017 was very productive, with several key achievements, including the commencement of our second Phase I CAR-T clinical trial utilizing CBMG’s proprietary and optimized CD19 construct, for the treatment of adult patients with relapsed or refractory CD19+ B-cell Acute Lymphoblastic Leukemia (ALL),” commented Tony Liu, Chief Executive Officer of CBMG. “The award of $2.29 million from the California Institute for Regenerative Medicine (CIRM) to support pre-clinical studies of AlloJoinTM in the U.S., moves forward our endeavor into the U.S. market and the development of an off-the-shelf stem cell product to treat Knee Osteoarthritis (KOA). The signing of a collaboration with GE Healthcare Life Sciences China to establish a joint laboratory within our own GMP facilities in Shanghai credits our GMP stature and capabilities. We are determined to build on our accomplishments from the first quarter to continue to strengthen our innovative pipelines and move our clinical assets into later stage development. We believe we are ahead of the competitive curve in addressing the manufacturing barriers to delivering consistent clinical grade cell therapies which have the potential to address the large cancer and knee osteoarthritis markets.” About Cellular Biomedicine Group Cellular Biomedicine Group, Inc. (NASDAQ:CBMG) develops proprietary cell therapies for the treatment of cancer and degenerative diseases. We conduct immuno-oncology and stem cell clinical trials in China using products from our integrated GMP laboratory. Our GMP facilities in China, consisting of twelve independent cell production lines, are designed and managed according to both China and U.S. GMP standards. CBMG recently commenced two Phase I human clinical trials in China using CAR-T to treat relapsed/refractory CD19+ B-cell Acute Lymphoblastic Leukemia (ALL) and Refractory Diffuse Large B-cell Lymphoma (DLBCL) as well as an ongoing Phase I trial in China for AlloJoinTM (CBMG’s “Off-the-Shelf” Allogeneic Human Adipose-derived Mesenchymal Stem Cell) for the treatment of Knee Osteoarthritis (KOA). CBMG was recently awarded $2.29 million from the California Institute for Regenerative Medicine (CIRM) to support pre-clinical studies of AlloJoinTM for Knee Osteoarthritis in the United States. The Company also recently announced a strategic partnership with GE Healthcare Life Sciences China to establish a joint technology laboratory to develop control processes for the manufacture of CAR-T and stem cell therapies. To learn more about CBMG, please visit www.cellbiomedgroup.com. Forward-Looking Statements Statements in this press release relating to plans, strategies, trends, specific activities or investments, and other statements that are not descriptions of historical facts may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking information is inherently subject to risks and uncertainties, and actual results could differ materially from those currently anticipated due to a number of factors, which include risks inherent in doing business, trends affecting the global economy, including the devaluation of the RMB by China in August 2015 and other risks detailed from time to time in CBMG’s reports filed with the Securities and Exchange Commission, quarterly reports on form 10-Q, current reports on form 8-K and annual reports on form 10-K. Forward-looking statements may be identified by terms such as "may," "will," "expects," "plans," "intends," "estimates," "potential," or "continue," or similar terms or the negative of these terms. Although CBMG believes the expectations reflected in the forward-looking statements are reasonable, they cannot guarantee that future results, levels of activity, performance or achievements will be obtained. CBMG does not have any obligation to update these forward-looking statements other than as required by law.
News Article | May 11, 2017
"These new follow-up results based on MRI scans are very encouraging, and strongly suggest that AST-OPC1 cells have engrafted in these patients post-implantation and have the potential to prevent lesion cavity formation, possibly reducing long-term spinal cord tissue deterioration after spinal cord injury," said Dr. Edward Wirth, Chief Medical Officer of Asterias. "Moreover, these new results add to the overall body of data supporting AST-OPC1's safety, and are consistent with safety data from our previous Phase 1 study in thoracic spinal cord injury and our extensive preclinical studies in more than 3,000 animals." Under the study protocol, patients are monitored by MRI scans at regular intervals over 12 months in order to assess status of the injection site and surrounding tissues. The Company will discuss the MRI data in more detail on its first quarter 2017 conference call and webcast on May 11, 2017 at 4:30 p.m. Eastern / 1:30 p.m Pacific. For both "listen-only" participants and those participants who wish to take part in the question-and-answer session, the call can be accessed by dialing 800-533-7619 (U.S./Canada) or 785-830-1923 (international) five minutes prior to the start of the call and providing the Conference ID 7610291. To access the live webcast, go to http://asteriasbiotherapeutics.com/inv_events_presentations.php. The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product. The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University. Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1. Additional information on the Phase 1/2a trial, including trial sites, can be found at www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com). AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site. In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. They also received low levels of immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with AST-OPC1. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all patients. In four of the five patients, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with cervical spine injuries, which represents the first targeted population for registration trials. Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at www.asteriasbiotherapeutics.com. Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/new-mri-data-from-asterias-ongoing-scistar-clinical-study-indicates-ast-opc1-cells-prevent-formation-of-damaging-lesion-cavities-in-patients-suffering-severe-spinal-cord-injury-300455768.html
Cellular Biomedicine Group CBMG Announces Publication Titled Target cell killing effects of CD20 targeting chimeric antigen receptor T cells derived from the type II anti CD20 antibody in Conjunction with 2017 ASCO Annual Meeting
News Article | May 19, 2017
SHANGHAI, China and CUPERTINO, Calif., May 19, 2017 (GLOBE NEWSWIRE) -- Cellular Biomedicine Group Inc. (NASDAQ:CBMG) (“CBMG” or the “Company”), a clinical-stage biopharmaceutical firm engaged in the development of effective immunotherapies for cancer and stem cell therapies for degenerative diseases, today announced the publication of an abstract exploring the application of B-cell antigen, CD20, for targeted Chimeric Antigen Receptor T cells (CAR-T) therapy. The abstract has been published in conjunction with the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, June 2 – 6, 2017. Abstract e14548, J Clin Oncol 35, 2017 - Target cell killing effects of CD20 targeting chimeric antigen receptor T cells derived from the type II anti-CD20 antibody. The complete text of the abstract can be found at http://abstracts.asco.org/199/AbstView_199_192206.html About Cellular Biomedicine Group Cellular Biomedicine Group, Inc. (NASDAQ:CBMG) develops proprietary cell therapies for the treatment of cancer and degenerative diseases. We conduct immuno-oncology and stem cell clinical trials in China using products from our integrated GMP laboratory. Our GMP facilities in China, consisting of twelve independent cell production lines, are designed and managed according to both China and U.S. GMP standards. CBMG recently commenced two Phase I human clinical trials in China using CAR-T to treat Refractory Diffuse Large B-cell Lymphoma (DLBCL), a Phase I human clinical trial to treat relapsed/refractory CD19+ B-cell Acute Lymphoblastic Leukemia (ALL), as well as an ongoing Phase I trial in China for AlloJoinTM (CBMG’s “Off-the-Shelf” Allogeneic Human Adipose-derived Mesenchymal Stem Cell) for the treatment of Knee Osteoarthritis (KOA). CBMG was recently awarded $2.29 million from the California Institute for Regenerative Medicine (CIRM) to support pre-clinical studies of AlloJoinTM for Knee Osteoarthritis in the United States. The Company also recently announced a strategic partnership with GE Healthcare Life Sciences China to establish a joint technology laboratory to develop control processes for the manufacture of CAR-T and stem cell therapies. To learn more about CBMG, please visit www.cellbiomedgroup.com. Forward-Looking Statements Statements in this press release relating to plans, strategies, trends, specific activities or investments, and other statements that are not descriptions of historical facts may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking information is inherently subject to risks and uncertainties, and actual results could differ materially from those currently anticipated due to a number of factors, which include risks inherent in doing business, trends affecting the global economy, including the devaluation of the RMB by China in August 2015 and other risks detailed from time to time in CBMG’s reports filed with the Securities and Exchange Commission, quarterly reports on form 10-Q, current reports on form 8-K and annual reports on form 10-K. Forward-looking statements may be identified by terms such as "may," "will," "expects," "plans," "intends," "estimates," "potential," or "continue," or similar terms or the negative of these terms. Although CBMG believes the expectations reflected in the forward-looking statements are reasonable, they cannot guarantee that future results, levels of activity, performance or achievements will be obtained. CBMG does not have any obligation to update these forward-looking statements other than as required by law.
News Article | May 22, 2017
"The loss of insulin-producing beta cells leads to type 1 diabetes, making it an ideal target for cell replacement therapy," said James Shapiro, MD, PhD, FRCSC, Director of the Clinical Islet Transplant Program, University of Alberta. "Islet transplants from scarce organ donors have offered great promise for those with unstable, high-risk type 1 diabetes, but the procedure has many limitations. With an unlimited supply of new islets that the stem cell-derived therapy promises, we have real potential to benefit far more patients with islet cell replacement." The PEC-Direct product candidate delivers stem cell-derived pancreatic progenitor cells, called PEC-01™ cells, in a device designed to allow direct vascularization of the cells in the device. After implantation, these cells are expected to proliferate and mature to human islet tissue including well-regulated beta cells producing insulin on demand. The direct vascularization of the implanted cells is expected to allow for robust and consistent engraftment but will necessitate the use of maintenance immune suppression therapy. The PEC-Direct product candidate is being developed for type 1 diabetes patients who have hypoglycemia unawareness, extreme glycemic lability, and/or severe hypoglycemic episodes. It is estimated that about 140,000 people in Canada and the U.S. have such high-risk type 1 diabetes. In addition to providing an unlimited supply of cells for implantation, the PEC-Direct approach has the potential to provide other advantages relative to cadaver islet transplants such as delivering a more consistent product preparation under quality-controlled cGMP conditions, with a more straightforward and safer mode of delivery. "ViaCyte was the first to differentiate human stem cells into glucose-responsive, insulin-producing cells, and now we are running the first and only clinical trials of stem cell-derived islet replacement therapies for type 1 diabetes," said Paul Laikind, PhD, President and CEO of ViaCyte. "While insulin therapy transformed type 1 diabetes from a death sentence to a chronic illness, it is far from a cure. Type 1 diabetes patients continue to deal with the daily impact of the disease and remain at risk for often severe long-term complications. This is especially true for the patients with high-risk type 1 diabetes, who face challenges such as hypoglycemia unawareness and life-threatening severe hypoglycemic episodes. These patients have a particularly urgent unmet medical need and could benefit greatly from cell replacement therapy." "Those living with hypoglycemia unawareness are at constant risk of life-threatening complications, and even death, because they do not sense the physical symptoms of low blood sugar," said Dr. Jeremy Pettus, Principal Investigator of the clinical trial and Assistant Professor of Medicine at UC San Diego. "An islet cell replacement therapy could be significant for patients with this type of high-risk diabetes." At UC San Diego, the trial will be performed at the School of Medicine's Altman Clinical Trials Research Institute with support from the California Institute for Regenerative Medicine (CIRM)'s Alpha Clinic and the Sanford Stem Cell Clinical Center. PEC-Direct is one of two product candidates in clinical development to treat patients with diabetes. ViaCyte's PEC-Encap™ (also known as VC-01) product candidate delivers the same cell therapy as PEC-Direct but uses a proprietary device called the Encaptra® Cell Delivery System that is designed to protect the cells from the patient's immune system. The PEC-Encap product candidate is being developed as a transformative therapy for all patients who require insulin to control their disease. Early clinical evidence with the PEC-Encap product supports the potential of the replacement cell therapy approach. However, the clinical results also indicate that further work to optimize the performance of the PEC-Encap product is required. ViaCyte recently announced a collaboration with W. L. Gore & Associates focused on modifying the Encaptra device to improve engraftment in patients. About PEC-01 Cells ViaCyte's PEC-01 cells are the biological component of both PEC-Direct and PEC-Encap product candidates. PEC-01 pancreatic progenitor cells are manufactured from pluripotent stem cells and are designed to further differentiate and mature after implantation, not only to fully functioning insulin-producing beta cells, but also to the other endocrine cell types that make up the normal healthy human pancreatic islet. This mixture of pancreatic cell types is expected to produce on-demand the necessary insulin, along with other hormones that are important for the regulation of glucose (sugar) in the blood including glucagon, somatostatin, and amylin. About ViaCyte ViaCyte is a privately-held regenerative medicine company developing novel cell replacement therapies as potential long-term diabetes treatments to reduce the risk of hypoglycemia and diabetes-related complications. ViaCyte's product candidates are based on the derivation of pancreatic progenitor cells, which are then implanted in a durable and retrievable cell delivery device. Once implanted and matured, these cells are designed to secrete insulin and other pancreatic hormones in response to blood glucose levels. ViaCyte has two products in development. The PEC-Direct™ product candidate delivers the pancreatic progenitor cells in a non-immunoprotective device and is being developed for type 1 diabetes patients who have severe hypoglycemic episodes, extreme glycemic lability, and/or impaired awareness of hypoglycemia. The PEC-Encap™ (also known as VC-01) product candidate delivers pancreatic progenitor cells in an immunoprotective device and is currently being evaluated in a Phase 1/2 trial in patients with type 1 diabetes who have minimal to no insulin-producing beta cell function. ViaCyte is headquartered in San Diego, California. The Company is funded in part by the California Institute for Regenerative Medicine (CIRM) and JDRF. For more information on ViaCyte, please visit www.viacyte.com and connect with ViaCyte on Twitter and Facebook. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/viacyte-receives-ind-allowance-from-fda-and-clearance-from-health-canada-to-commence-international-clinical-trial-of-pec-direct-cell-therapy-for-high-risk-type-1-diabetes-300461166.html
News Article | April 25, 2017
Irvine, Calif., April 24, 2017 -- Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease. The finding marks an important step in the use of induced pluripotent stem (iPS) cells for targeted approaches to better understand and potentially treat neurological diseases such as Alzheimer's. These iPS cells are derived from existing adult skin cells and show increasing utility as a promising approach for studying human disease and developing new therapies. Skin cells were donated from patients at the UCI Alzheimer's Disease Research Center. The study, led by Edsel Abud, Wayne Poon and Mathew Blurton Jones of UCI, used a genetic process to reprogram these cells into a pluripotent state capable of developing into any type of cell or tissue of the body. The researchers then guided these pluripotent cells to a new state by exposing the cells to a series of differentiation factors which mimicked the developmental origin of microglia. The resulting cells act very much like human microglial cells. Their study appears in the current issue of Neuron. In the brain, microglia mediate inflammation and the removal of dead cells and debris. These cells make up 10- to 15-percent of brain cells and are needed for the development and maintenance of neural networks. "Microglia play an important role in Alzheimer's and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimer's-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies," said Blurton-Jones, an assistant professor of the Department of Neurobiology & Behavior and Director of the ADRC iPS Core. "Scientists have had to rely on mouse microglia to study the immunology of AD. This discovery provides a powerful new approach to better model human disease and develop new therapies," added Poon, a UCI MIND associate researcher. Along those lines, the researchers examined the genetic and physical interactions between Alzheimer's disease pathology and iPS-microglia. They are now using these cells in three-dimensional brain models to understand how microglia interact with other brain cells and influence AD and the development of other neurological diseases. "Our findings provide a renewable and high-throughput method for understanding the role of inflammation in Alzheimer's disease using human cells," said Abud, an M.D./Ph.D. student. "These translational studies will better inform disease-modulating therapeutic strategies." Blurton Jones, Abud and Poon are with UCI's Institute for Memory Impairments and Neurological Disorders (UCI MIND). Ricardo Ramirez, Eric Martinez, Cecilia Nguyen, Sean Newman, Vanessa Scarfone, Samuel E. Marsh, Cristhian Fimbres, Chad A. Caraway, Ali Mortazavi, Michael Cahalan, Brian Cummings, Gianna Fote, Andriy Yeromin and Anshu Agrawal with UCI; Luke Healy and Jack Antel with McGill University, Montreal; Rakez Kayed with the University of Texas Medical Branch, Galveston, Texas; Karen Gylys with UCLA; and Abdullah Madany and Monica Carson with UC Riverside contributed to the study. The National Institutes of Health, the California Institute for Regenerative Medicine, and the Susan Scott Foundation provided support.
News Article | April 26, 2017
When California voters approved US$3 billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinson’s disease and spinal-cord injuries. Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research. If they don’t, that could leave hundreds of scientists without support, and strand potentially promising therapies before they reach the market. “It’s an issue of great concern,” says Jonathan Thomas, chair of the board for the California Institute for Regenerative Medicine (CIRM) in Oakland. CIRM is now doling out its final $650 million, and its leaders are seeking money from the private sector to carry projects beyond 2020, when the money will run out. Advocates are also surveying voters to determine whether a new request for funding stands a chance in state elections next year. But critics argue against this way of funding research. California voters saw major opportunities for stem cells in 2004 when they passed Proposition 71, which included an agreement to create the corporation that became CIRM. The move was a reaction to then-US president George W. Bush’s decision in 2001 to restrict federal funds for work on human embryonic stem cells. Since CIRM rolled out its first grants in 2006, it has funded more than 750 projects and reported alluring results from clinical trials. In March, a trial partially funded by CIRM showed that nine out of ten children born with severe combined immunodeficiency — or ‘bubble-boy disease’ — a potentially lethal condition in which a person’s immune system does not function properly, were doing well up to eight years after treatment (K. L. Shaw et al. J. Clin. Invest. http://doi.org/b6bp; 2017). They no longer need injections to be able to go to school, play outside or survive colds and other inevitable infections. A dozen facilities constructed by CIRM have helped to push California to the forefront of research on ageing and regenerative medicine. Many grant recipients were early-career academics who had not been able to enter the stem-cell field previously because of the federal restrictions — which were loosened in 2009 — and the high cost of getting started in this kind of work. That barrier makes it difficult for researchers to gather the preliminary data typically required to win grants from the US National Institutes of Health (NIH). To milk its remaining $650 million, CIRM partnered last year with the contract-research organization QuintilesIMS in Durham, North Carolina, to carry out clinical trials. CIRM leaders hope that this move will help to guide 40 novel therapies into trials by 2020. Bob Klein, the property developer who put Proposition 71 on the ballot and established CIRM, isn’t waiting for the money to run out. He leads an advocacy group, Americans for Cures, which will soon poll voters to see whether they would approve another $5 billion in funding. If it looks like at least 70% of Californians support that plan, he’ll start a campaign to put another initiative on the ballot in 2018. Klein hopes that Californians will rise in support of science at a time when the Trump administration has proposed drastic cuts to the NIH budget. If public enthusiasm is not so strong, Klein says, he’ll aim for the 2020 elections, when voter turnout should be higher because it will coincide with the next presidential race. Currently, CIRM’s leaders are seeking other sources of support. “The majority of our projects will not be ripe for interest from big pharma and the venture-capitalist community by the time we run out of funds,” Thomas says. He has been courting large philanthropic foundations and wealthy individuals to raise money to continue the work. John Simpson, who directs stem-cell oversight work at the advocacy group Consumer Watchdog in Santa Monica, California, plans to oppose any effort to extend CIRM. “I acknowledge their scientific advances, but we should not let a flawed process go further,” he says. Simpson dislikes the model of using a vote to secure research funding through public bonds, because then the state lacks budgetary control. Oversight of CIRM has been a problem in the past. In 2012, the US Institute of Medicine found that some scientists vetting grant proposals for CIRM had conflicts of interest. In response, CIRM altered its procedures — but the public still felt betrayed. Jim Lott, a member of the state board that oversees CIRM’s finances, says that he is not satisfied with the changes. He also argues that CIRM may not have been strategic enough in directing research. “Some people say if they had a better focus, they might have achieved cures.” But researchers argue that expectations for cures after only a decade are unrealistic, given the typical pace of drug development. “It would be a catastrophe for California if people say CIRM did not do what it was expected to do,” says Eric Verdin, president of the Buck Institute for Research on Aging in Novato, California. “They’ve built the foundation for the field and attracted people from around the world — you can’t just now pull the plug.”
News Article | April 17, 2017
CHARLOTTESVILLE, Va., April 13, 2017 - For Mazhar Adli, the little glowing dots dancing about on the computer screen are nothing less than the fulfillment of a dream. Those fluorescent dots, moving in real time, are set to illuminate our understanding of the human genome, cancer and other genetic diseases in a way never before possible. Adli, of the University of Virginia School of Medicine's Department of Biochemistry and Molecular Genetics, has developed a way to track genes inside living cells. He can set them aglow and watch them move in three dimensions, allowing him to map their positions much like star charts record the shifting heavens above. And just as the moon influences the tides, the position of genes influences the effects they have; thus, 3D maps of gene locations could lead scientists to a vastly more sophisticated appreciation of how our genes work and interact -- and how they affect our health. "This has been a dream for a long time," Adli said. "We are able to image basically any region in the genome that we want, in real time, in living cells. It works beautifully. ... With the traditional method, which is the gold standard, basically you will never be able to get this kind of data, because you have to kill the cells to get the imaging. But here we are doing it in live cells and in real time." DNA is often depicted as tidy strands stretched out in straight lines. But in reality, our DNA is clumped up inside the nuclei of our cells like cooked spaghetti. "We have two meters of DNA folded into a nucleus that is so tiny that 10,000 of them will fit onto the tip of a needle," Adli explained. "We know that DNA is not linear but forms these loops, these large, three-dimensional loops. We want to basically image those kind of interactions and get an idea of how the genome is organized in three-dimensional space, because that's functionally important." Thinking about DNA as a neat line, he noted, can create misconceptions about gene interactions. Two genes that are far apart in a linear diagram may actually be quite close when folded up inside the cell's nucleus, and that can affect what they do. He used a map analogy: "That's how we believe an element that appears to be in Los Angeles is regulating an element in Virginia - [when the DNA is folded up,] they're not actually that far apart." Adli's new approach, developed in conjunction with colleagues at UVA and the University of California, Berkeley, uses the CRISPR gene editing system that has proved a sensation in the science world. The researchers flag specific genomic regions with fluorescent proteins and then use CRISPR to do chromosome imaging. If they want, they can then use CRISPR to turn genes on and off, using the imaging approach to see what happens. The new method overcomes longstanding limitations of gene imaging. "We were told we would never be able to do this," Adli said. "There are some approaches that let you look at three-dimensional organization. But you do that experiment on hundreds of millions of cells, and you have to kill them to do it. Here, we can look at the single-cell level, and the cell is still alive, and we can take movies of what's happening inside." The business of growing cells just to kill them is both time consuming and a poor way to figure out what was happening with the DNA inside them, he said. It is like trying to figure out the rules of football by looking at blurry pictures of a game. Adli's new approach, on the other hand, lets him sit back and watch the plays unfold in real time. "It's a super exciting thing to be able to do," he said. Adli and his team have described their new method in an article in the scientific journal Nature Communications, making it available to scientists around the world. The paper was authored by Peiwu Qin, Mahmut Parlak, Cem Kuscu, Jigar Bandaria, Mustafa Mir, Karol Szlachta, Ritambhara Singh, Xavier Darzacq, Ahmet Yildiz and Adli. The work was supported by the V Foundation for Cancer Research; the UVA Cancer Center; the National Institutes of Health, grants U54-DK107980, U01-EB021236 and GM094522; the National Science Foundation; and the California Institute for Regenerative Medicine.
Knoepfler P.S.,University of California at Davis |
Knoepfler P.S.,California Institute for Regenerative Medicine
Advanced Drug Delivery Reviews | Year: 2015
The phrase "bench-to-bedside" is commonly used to describe the translation of basic discoveries such as those on stem cells to the clinic for therapeutic use in human patients. However, there is a key intermediate step in between the bench and the bedside involving governmental regulatory oversight such as by the Food and Drug Administration (FDA) in the United States (US). Thus, it might be more accurate in most cases to describe the stem cell biological drug development process in this way: from bench to FDA to bedside. The intermediate development and regulatory stage for stem cell-based biological drugs is a multifactorial, continually evolving part of the process of developing a biological drug such as a stem cell-based regenerative medicine product. In some situations, stem cell-related products may not be classified as biological drugs in which case the FDA plays a relatively minor role. However, this middle stage is generally a major element of the process and is often colloquially referred to in an ominous way as "The Valley of Death". This moniker seems appropriate because it is at this point, and in particular in the work that ensues after Phase 1, clinical trials that most drug product development is terminated, often due to lack of funding, diseases being refractory to treatment, or regulatory issues. Not surprisingly, workarounds to deal with or entirely avoid this difficult stage of the process are evolving both inside and outside the domains of official regulatory authorities. In some cases these efforts involve the FDA invoking new mechanisms of accelerating the bench to beside process, but in other cases these new pathways bypass the FDA in part or entirely. Together these rapidly changing stem cell product development and regulatory pathways raise many scientific, ethical, and medical questions. These emerging trends and their potential consequences are reviewed here. © 2014 Elsevier B.V.
Yuen B.T.K.,University of California at Davis |
Yuen B.T.K.,California Institute for Regenerative Medicine |
Knoepfler P.S.,University of California at Davis |
Knoepfler P.S.,California Institute for Regenerative Medicine
Cancer Cell | Year: 2013
A host of cancer types exhibit aberrant histone modifications. Recently, distinct and recurrent mutations in a specific histone variant, histone H3.3, have been implicated in a high proportion of malignant pediatric brain cancers. The presence of mutant H3.3 histone disrupts epigenetic posttranslational modifications near genes involved in cancer processes and in brain function. Here, we review possible mechanisms by which mutant H3.3 histones may act to promote tumorigenesis. Furthermore, we discuss how perturbations in normal H3.3 chromatin-related and epigenetic functions may more broadly contribute to the formation of human cancers. © 2013 Elsevier Inc.