‘Undruggable’ cancer may be druggable after all: New target identified

June 17, 2013 Harvard Stem Cell Institute (HSCI) researchers have identified in the most aggressive forms of cancer a gene known to regulate embryonic stem cell self-renewal, beginning a creative search for a drug that can block its activity.

The gene, SALL4, gives stem cells their ability to continue dividing as stem cells rather than becoming mature cells. Typically, cells only express SALL4 during embryonic development, but the gene is re-expressed in nearly all cases of acute myeloid leukemia and 10 to 30 percent of liver, lung, gastric, ovarian, endometrial, and breast cancers, strongly suggesting it plays a role in tumor formation.

In work published in the New England Journal of Medicine, two HSCI-affiliated labs -- one in Singapore and the other in Boston -- show that knocking out the SALL4 gene in mouse liver tumors, or interfering with the activity of its protein product with a small inhibitor, treats the cancer.

"Our paper is about liver cancer, but it is likely true about lung cancer, breast cancer, ovarian cancer, many, many cancers," said HSCI Blood Diseases Program leader Daniel Tenen, who also heads a laboratory at the Cancer Science Institute of Singapore (CSI Singapore). "SALL4 is a marker, so if we had a small molecule drug blocking SALL4 function, we could also predict which patients would be responsive."

Studying the therapeutic potential of a transcription factor is unusual in the field of cancer research. Transcription factors are typically avoided because of the difficulty of developing drugs that safely interfere with genetic targets. Most cancer researchers focus their attention on kinases.

The HSCI researchers' inquiry into the basic biology of the SALL4 gene, however, revealed another way to interfere with its activity in cancer cells. The gene's protein product is responsible for turning off a tumor-suppressor gene, causing the cell to divide uncontrollably. Using this knowledge, the researchers demonstrated that targeting the SALL4 protein with druglike molecules could halt tumor growth. "The pharmaceutical companies decided that if it is not a kinase and it is not a cell surface molecule, then it is 'undruggable,' " Tenen said. "To me, if you say anything is 'undoable,' you are limiting yourself as a biomedical scientist."

Earlier this year, Tenen's co-author, HSCI-affiliated faculty member Li Chai, a Harvard Medical School assistant professor of pathology at Brigham and Women's Hospital, published a paper in the journal Blood, reporting that a SALL4 inhibitor has similar treatment potential in leukemia cells.

Chai took blood samples from patients with acute myeloid leukemia, treated the leukemic cells with the inhibitor that interferes with SALL4 protein activity, and then transplanted the blood into mice. The result was a gradual regression of the same cancer in mice.

"I am excited about being on the front line of this new drug development," Chai said. "As a physician-scientist, if I can find a new class of drug that has very low toxicity to normal tissues, my patients can have a better quality of life."

Chai and Tenen are now working with HSCI Executive Committee member Lee Rubin, the Harvard Institute of Chemistry and Cell Biology, and James Bradner of Dana-Farber Cancer Institute, another HSCI-affiliated faculty member, to overcome the technical challenges of drug development and demonstrate the potential of SALL4 interference to treat other forms of cancer.

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'Undruggable' cancer may be druggable after all: New target identified

VistaGen Therapeutics Presents CardioSafe 3D(TM) and LiverSafe 3D(TM) Developments at International Society of Stem …

SOUTH SAN FRANCISCO, CA--(Marketwired - Jun 17, 2013) - VistaGen Therapeutics, Inc. (OTCQB: VSTA), a biotechnology company applying stem cell technology for drug rescue, predictive toxicology and drug metabolism assays, presented key developments involving its CardioSafe 3D and LiverSafe 3D bioassay systems in poster presentations at the 11th Annual Meeting of the International Society of Stem Cell Research(ISSCR), the largest forum for stem cell and regenerative medicine professionals from around the world, held June 12 to 15, 2013, in Boston, Massachusetts.

Dr. Hai-Qing Xian, Senior Scientist, presented VistaGen's poster entitled "Cardiotoxicity Assessment of Anti-Cancer Kinase Inhibitors using Human Pluripotent Stem Cell-Derived Cardiomyocyte Based Assays," which detailed important developments demonstrating that CardioSafe 3D, VistaGen's high throughput, human heart cell-based bioassay, is a clinically predictive system for preclinical cardiac safety screening of anti-cancer drug candidates, including small molecule kinase inhibitors (KIs), a new category of drugs that have revolutionized cancer therapy due to decreased systemic toxicity and increased target cell efficacy compared to classic cancer drugs, as well as other therapeutic compounds. VistaGen demonstrated the utility of CardioSafe 3D to detect cardiac toxicities of well-known anti-cancer KIs, including imatinib, dasatinib, sunitinib, erlotinib and temsirolimus, which have been associated with adverse clinical cardiac events that were not detected during the drug development process. As demonstrated in the poster presentation, CardioSafe 3D successfully detected cardiotoxicity induced by representative compounds from different KI categories.Additionally, the bioassay system provided clues to the major mechanisms of cardiac cytotoxicity induced by each compound, thus enabling not only the identification of toxicities early in the drug development process, but also discovery of potential mechanisms of action.

Dr. Kristina Bonham, Senior Scientist, Hepatocyte Biology Project Leader, presented VistaGen's poster entitled "Semi-quantitative assay of CYP3A4 allows the identification and selection of mature human stem cell derived hepatocytes," which detailed developments indicating that LiverSafe 3D, VistaGen's human liver cell-based bioassay, can monitor the induction of the key metabolic enzyme, CYP3A4, and its expression level over time. Using an optimized protocol for the differentiation of hepatocyte-like cells, VistaGen demonstrated levels of CYP3A4 mRNA approaching that in human adult liver on a per cell basis. The reported data suggest that VistaGen's liver cells have many of the functional properties of mature adult liver cells, enabling multiple functional analyses and providing a powerful system to evaluate the effects of drug candidates on CYP3A4 expression and liver function, offering a valuable aid for assessing potential drug candidates for toxicity and adverse drug-drug interactions.

H. Ralph Snodgrass, PhD, VistaGen's President and Chief Scientific Officer, stated, "For the first time, our technology has caught up with the dreams and visions we had 15 years ago when we founded VistaGen.We now have the type and quality of human cell-based biological assay systems that provide real insight into both the therapeutic and toxic effects of new drug candidates long before they are ever tested in humans. Next-generation biological assays can now provide important preclinical human data that will increase the probability of selecting safer and effective therapeutics for clinical development."

"It is evident from the mood, tone and scientific discussions throughout the ISSCR conference that this is the most exciting time in the history of stem cell research," continued Dr. Snodgrass. "We anticipate that we will see an explosion over the next ten years in the contribution of human pluripotent stem cell-based biological assays to drug development, in parallel with phenomenal advancements in the therapeutic uses of mature cells and tissues derived from human pluripotent stem cells to treat some of the most intractable human diseases and conditions. Our team is truly fortunate and excited about being a part of this transformational process."

About VistaGen Therapeutics

VistaGen is a biotechnology company applying human pluripotent stem cell technology for drug rescue, predictive toxicology and drug metabolism screening. VistaGen's drug rescue activities combine its human pluripotent stem cell technology platform, Human Clinical Trials in a Test Tube, with modern medicinal chemistry to generate novel, safer chemical variants (Drug Rescue Variants) of once-promising small molecule drug candidates. These are drug candidates discontinued by pharmaceutical companies, the U.S. National Institutes of Health (NIH) or university laboratories, after substantial investment in discovery and development, due to heart or liver toxicity or metabolism issues. VistaGen uses its pluripotent stem cell technology to generate early indications, or predictions, of how humans will ultimately respond to new drug candidates before they are ever tested in humans, bringing human biology to the front end of the drug development process.

VistaGen's small molecule prodrug candidate, AV-101, has completed Phase 1 development for treatment of neuropathic pain. Neuropathic pain, a serious and chronic condition causing pain after an injury or disease of the peripheral or central nervous system, affects millions of people worldwide.

Visit VistaGen at http://www.VistaGen.com, follow VistaGen at http://www.twitter.com/VistaGen or view VistaGen's Facebook page at http://www.facebook.com/VistaGen.

Cautionary Statement Regarding Forward Looking Statements

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VistaGen Therapeutics Presents CardioSafe 3D(TM) and LiverSafe 3D(TM) Developments at International Society of Stem ...

Qatar in breakthrough diabetes stem cell therapy

Manama: A potentially significant breakthrough in the treatment of diabetes has been made by a team of Qatar-based scientists. The scientists at Qatar Biomedical Research Institute (QBRI), in collaboration with researchers at Imperial College London, have reportedly discovered a new way to instruct isolated stem cells in a laboratory setting to secrete insulin when it is needed to maintain the correct sugar level in the bodys circulation.

Diabetes is a world-wide health problem, and it is especially prevalent in Qatar, Dr Abdul Ali Haoudi, the Executive Director of QBRI and a co-author of the study, said. People with diabetes face serious medical complications, including heart disease and kidney failure. This discovery has the potential to reduce this burden by harnessing the bodys own stem cells to secrete insulin as needed to maintain proper blood sugar levels in the body. This research represents the first promising steps toward a new treatment, but it will need to go through the clinical validation before it is declared a viable therapy, he said.

The findings have just been published in Molecular Therapy-Nucleic Acids, the official journal of the American Society of Gene and Cell Therapy.

Dr Nagy Habib, Scientific Director of the Stem Cell and Regenerative Medicine Centre at QBRI, is the lead investigator of the team of scientists at QBRI and Imperial College London that made the discovery.

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In a healthy person, insulin is produced by the pancreas in a constant proportion to remove excess glucose, or sugar, from the blood, Haoudi explained. When a person consumes more sugar-rich food, the insulin-producing cells in the pancreas (called beta cells) secrete more insulin. When a person eats less sugar, the beta cells produce less insulin. The stem cells engineered by the QBRI team behave in the same way, secreting more or less insulin, depending on glucose levels in the blood, he said.

The studies have been supported by QBRI, a member of the Qatar Foundation for Education, Science and Comnmunity Development, established in 2012 to tackle diseases of major worldwide importance, and particularly prevalent in Qatar and the Middle East, such as diabetes and certain forms of cancer.

QBRI which has a specific focus on developing translational biomedical research and biotechnology, has set up eight research centres: Stem Cell and Regenerative Medicine Research Centre, Genomic Medicine and Systems Biology Research Centre, Gene-based Therapy Research Centre, Biomedical Engineering Research Centre, Diabetes Research Centre, Cancer Research Centre, Genetic Diseases Research Centre, and the Qatar Biobank.

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Qatar in breakthrough diabetes stem cell therapy

A paralyzed German Shepard receives revolutionary combination stem cell treatment! – Video

A paralyzed German Shepard receives revolutionary combination stem cell treatment!
Brando, a 9 year-old German Shepard received combination stem cell therapy today at Paradise Animal Clinic by Dr. Jose Gorostiza (surgeon) and Dr. Jaime Pausa (practice owner). Brando has been...

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A paralyzed German Shepard receives revolutionary combination stem cell treatment! - Video

Sandy Andolong credits stem cell treatment for revitalized health; supports daughter Mariel’s plan to join showbiz

Sandy Andolong credits stem cell treatment for revitalized health; supports daughter Mariel's plan to join showbiz

Marami ang natuwa sa mas batang hitsura at mas malusog na pangangatawan ngayon ni Sandy Andolong.

Kinuwento nga nito na sumailalim siya sa stem cell treatment kaya malaki ang naging improvement ng kanyang kalusugan.

Kung matatandaan ay nagkaroon ng maraming sakit si Sandy noong 2003.

She was diagnosed with kidney maladies, her large intestines had lacerations, her uterus was inflamed, there was a polyp in her gall bladder and her pituitary gland had a disorder resulting in abnormal lactation.

Muntik na nga raw sumailalim sa isang kidney transplant operation ang butihing asawa ni Christopher de Leon.

Pero dahil sa malakas na panalangin nila sa Panginoon, nagkaroon ng kasagutan ang kanilang mga dasal and ten years after, maganda na ang kalusugan ng aktres.

I went through six months of stem cell treatment. Dito lang naman sa atin ginawa kaya hindi na namin kailangang pumunta sa ibang bansa.

After the treatment, mas lumakas na ang katawan ko kasi nga bagong mga cells ang nasa loob ng katawan ko.

I feel more energized at parang nagdahilan lang ako sa sakit ko before.

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Sandy Andolong credits stem cell treatment for revitalized health; supports daughter Mariel's plan to join showbiz

Scientists challenge patent ban for embryonic stem cell research

Scientists and lawyers in Britain are challenging a European ban on the patenting of embryonic stem cells which they believe is blocking the development of new treatments for a range of illnesses including diabetes, heart disease and Parkinsons.

They have been joined by a High Court judge who has asked the Court of Justice of the European Union in Luxembourg to clarify its decision to prevent the patenting of stem cell research involving the use and destruction of human embryos. Medical researchers and biotechnology firms are incensed by the European courts ban on stem cell patents. They say it is deterring investment in Europe while scientists in Asia forge ahead with research into new medical treatments based on embryonic stem cells.

Sir Ian Wilmut, who cloned Dolly the sheep, and Professor Austin Smith of the Wellcome Trust Centre for Stem Cell Research at Cambridge University, said that banning patents has effectively removed the protection of intellectual property that is crucial for commercial investment.

Their concerns have now been voiced by Henry Carr QC, a deputy judge of the High Court, who questioned whether the European court really understood the scientific basis of its ban, which it issued last year.

The European court ruled that German scientists could not patent a technique based on human embryonic stem cells because it involved the destruction of something capable of commencing the process of development of a human being in other words a human embryo.

However, Mr Carr said that the definition of a human embryo used by the court may be too broad because it included types of artificially created embryos that are not capable of developing into a foetus.

Stem cells have the potential to revolutionise the treatment of human disease. Because of their capacity to differentiate into almost any type of adult cell, human stem cells open the door to a wide variety of new therapies and other medical applications, Mr Carr said in his judgment on a patent appeal case. However, to exclude [from patentability] processes of development which are incapable of leading to a human being does not, in my view, strike a balance at all It is more akin to a total exclusion from patent protection of the fruits of stem cell research, to the detriment of European industry and public health.

Professor Pete Coffey of University College London, who is conducting one of the first clinical trials of stem cells to treat progressive blindness, said the ban on patenting stem cell research could harm its future development in Britain and Europe. It creates [funding problems for] this kind of translational research taking ideas from the lab into the clinic, he said.

The US Supreme Court ruled yesterday that genes extracted from the human body cannot be patented.

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Scientists challenge patent ban for embryonic stem cell research