H3 Biomedicine Launches To Discover And Develop Next Generation Cancer Treatments

H3 Biomedicine Inc. announced that it has launched research and development operations in Cambridge, Massachusetts. H3 Biomedicine will undertake a comprehensive approach to breakthrough oncology treatments based on two primary principles: 1) the genetics of patients' cancers can reveal drug targets tailored to their cancers and 2) the advances in modern chemistry enable the discovery of new classes of safe and effective drugs against these targets. Researchers worldwide are for the first time understanding the genetic basis of human cancers, and H3 Biomedicine will use that knowledge to generate new cancer treatments aimed at fulfilling the promise of personalized cancer medicine.

H3 Biomedicine will achieve its goals through a unique relationship with the pharmaceutical company Eisai Inc. Eisai has pledged up to $200 million in research funding to H3 Biomedicine, as well as additional support for the clinical development of H3 Biomedicine programs. In addition, H3 Biomedicine will benefit from access to many of Eisai's drug development capabilities, allowing H3 Biomedicine to focus on first-in-class drug discovery innovation.

H3 Biomedicine's scientific founders are renowned researchers Stuart L. Schreiber, PhD, and Todd R. Golub, MD, who will serve as academic advisors to the company. As founding members of the Broad Institute of Harvard and MIT, Drs. Schreiber and Golub have transformed the way medical research is done.

Dr. Schreiber's conceptual, experimental and leadership contributions have had a significant impact on chemistry, biology and medicine. Already, three new anti-cancer drugs that target cancer proteins discovered by Schreiber have been approved. In addition to his role at the Broad Institute, Dr. Schreiber serves as Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University and an Investigator at the Howard Hughes Medical Institute.

Dr. Golub is a world leader in the genomic characterization of cancer. His work focuses on using the human genome to understand the biological and clinical challenges facing cancer medicine, and he has pioneered the use of genomic approaches to cancer biology and cancer drug discovery. In addition to his role at the Broad Institute, Dr. Golub is Charles A. Dana Investigator at the Dana-Farber Cancer Institute, Professor of Pediatrics at Harvard Medical School, and an Investigator at the Howard Hughes Medical Institute.

Unlike many biotech start-ups, H3 Biomedicine will have a unique relationship with Eisai that provides access to resources and capabilities of an established pharmaceutical company, while also encouraging and rewarding innovative and entrepreneurial spirit. Furthermore, the Eisai affiliation will enable H3 Biomedicine to take a longer-term view of its drug discovery activities than is typical of many venture-backed start-up companies. This model is thus intended to capture the best of both the biotech and large pharmaceutical company worlds.

Eisai's relationship with H3 Biomedicine also strengthens Eisai's commitment to advancing human health care through the development of medicines to treat unmet medical needs. "Our alliance with H3 Biomedicine represents a new approach to cancer drug discovery that holds enormous promise to help patients worldwide suffering from cancer," said Haruo Naito, President and CEO of Eisai Co., Ltd.

Kentaro Yoshimatsu, PhD, who serves as Chief Scientific Officer of Eisai Product Creation Systems, will take on the additional role of President of H3 Biomedicine. In this capacity, Dr. Yoshimatsu will ensure that H3 Biomedicine's unique business model is positioned for success while a search is conducted to identify a world-class leader to serve as Chief Scientific Officer of H3 Biomedicine.

In addition to its unique business model, the establishment of H3 Biomedicine represents a new paradigm for cancer drug discovery in which the ability to understand cancer genomes, coupled with advances in small-molecule science will serve as the foundation for creating the next generation of oncology treatments. H3 Biomedicine will follow a disciplined approach to drug discovery, relating the genetics of specific cancers to their unique vulnerabilities, and developing drugs that target those vulnerabilities. Using biomarkers to guide clinical development, H3 Biomedicine intends to enable the practice of personalized medicine for oncology patients. This biomarker-driven model for drug development is also expected to shorten clinical development timelines and reduce clinical trial costs.

According to the World Health Organization, cancer is the leading cause of death worldwide, accounting for 7.9 million deaths in 2007. Death from cancer is projected to rise, with an estimated 12 million deaths expected in 2030.

Magnesium sulfate Precautions on Pregnancy

Magnesium sulfate has been assigned to pregnancy category A by the FDA. Studies in pregnant women have not shown evidence of fetal risk if magnesium sulfate is administered during any trimesters of pregnancy. However, because studies cannot completely rule out the possibility of harm, magnesium sulfate injection is only recommended for use during pregnancy when benefit outweighs risk.

Newborns may show signs of magnesium toxicity (i.e. respiratory and/or neuromuscular depression) if the mother has received intravenous magnesium sulfate prior to delivery (especially if for a period of longer than 24 hours). Equipment for assisted ventilation as well as intravenous calcium should be immediately available for the first 24 to 48 hours after delivery. One study has reported that maternal magnesium sulfate treatment is associated with reduced brain blood flow perfusion in preterm infants. However, intravenous magnesium sulfate did not lead to lower neonate apgar scores in a study of women treated for pre-eclampsia even though the newborn's cord level indicated hypermagnesemia. The mean cord magnesium level (5.3 mEq/100 mL) was equivalent to the mean maternal serum level. Cord serum magnesium levels do not usually correlate with infant toxicity. The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 141 of which had been exposed to magnesium sulfate during pregnancy. No reports or evidence were found linking congenital birth defects with magnesium sulfate. A study of 7000 offspring of mothers treated for pre-eclampsia noted no adverse effects due to magnesium sulfate therapy in the fetuses or newborns. One study compared the newborn of women with pregnancy-induced hypertension who received magnesium sulfate with women who did not receive treatment. Neurologic behavior in the infants was similar in both groups except that the exposed group had decreased active tone of the neck extensors the day after birth. Long-term infusions of magnesium (such as those used for tocolysis) may lead to persistent hypocalcemia and congenital rickets in the fetus. Case reports of 2 women receiving 9 or 14 weeks of intravenous magnesium therapy prior to delivery noted bony abnormalities. Slight hypocalcemia occurred in one infant. Both infants were treated with intravenous calcium for 3 to 5 days and then given bottle feedings without added calcium or vitamin D. The only noted physical abnormality at 3 year follow-up was dental enamel hypoplasia in one infant. Fetal hypermagnesemia may have decreased parathyroid hormone release and lead to fetal hypocalcemia. The combination of in-utero acquired magnesium sulfate and gentamicin (administered after birth) may lead to respiratory depression in the newborn. The mechanism of this interaction is not known. Animal studies have confirmed this drug interaction.

Marijuana's Anti-Cancer Properties

The active ingredient in marijuana appears to target cancerous brain cells for destruction while leaving healthy cells alone, according to a study conducted by researchers from the Complutense University in Madrid, and published in theJournal of Clinical Investigation.
Researchers first conducted an experiment in mice that had been engineered to carry three different grafts of human brain cancer. They injected the mice daily with the molecule tetrahydrocannabinol (THC) near the site of the tumors once each day. The chemical appeared to stimulate the cancerous cells to engage in a process known as autophagy, in which cells initiate their own breakdown.
"These results may help to design new cancer therapies based on the use of medicines containing the active principle of marijuana and/or in the activation of autophagy," researcher Guillermo Velasco said.
THC belongs to a class of chemicals known as cannabinoids, named after the cannabis (marijuana) plant in which they occur. It is the chemical responsible for the psychoactive effects of marijuana consumption.
In a followup experiment, the researchers extracted and analyzed brain tissue from two patients with an aggressive form of brain cancer known as "recurrent glioblastoma multiforme." The patients were treated with THC for either 26 or 30 days, then the researchers extracted and analyzed another sample.
After examining the brain tissue under an electron microscope, the researchers discovered that THC treatment resulted in death of cancerous cells but had no effect on healthy ones. The researchers were also able to discover the signaling pathway by which THC acts.
The research opens up the possibility that cannabinoid research could yield "a new family of potential antitumoral agents," the researchers wrote.
Glioblastoma multiforme is the most common and aggressive form of primary brain tumor. Without treatment, the average patient lives only three months after being diagnosed with the cancer. Treatment extends the average life expectancy after diagnosis by less than a year.

Hospital Admissions In Children With Gastroenteritis

Gastroenteritis is an infection, often caused by a virus, that causes vomiting and diarrhea. It is often popularly called “stomach flu” and is a very common ailment in children during the winter months.
In the emergency department at UNC Hospitals, five to 10 children a day are seen with symptoms of gastroenteritis, said Dr. Michael J. Steiner, assistant professor of pediatrics and a co-author of the study.
Persistent vomiting from acute gastroenteritis can be very frightening to children and their families and also poses a risk of dehydration. Current practice guidelines do not recommend that doctors give medications to children with gastroenteritis, but several recent studies suggest that ondansetron might be helpful.
In addition, Steiner said, many doctors are already prescribing ondansetron “off-label” for children with gastroenteritis. It has not been approved by the Food and Drug Administration for that indication, although it is approved for treating nausea caused by chemotherapy in cancer patients.
To find out if there was valid scientific support for giving antiemetics to children with gastroenteritis, DeCamp, Steiner and two UNC colleagues -- Dr. Julie S. Byerly, assistant professor of pediatrics, and medical student Nipa Doshi -- conducted a systematic review of all the medical literature studying the use of antiemetics for gastroenteritis.
The 11 identified previously published studies evaluated the safety and effectiveness of seven different antiemetics that were given to children seen in hospital emergency departments.  The authors found that antiemetics other than ondansetron should not be used in children with gastroenteritis.
A meta-analysis (a statistical way to combine different studies) found that ondansetron, which is sold under the brand name Zofran and is available as an intravenous infusion, tablet, disintegrating tablet or in liquid forms, reduced further vomiting after receipt in the emergency department. Importantly, it also reduced the likelihood that children would require intravenous fluids by nearly two-thirds, and halved the risk of immediate hospital admission. Ondansetron also had one down side:  It was found to increase diarrhea in 3 of the 6 studies.  However, the authors found this increased diarrhea did not appear to cause an increased need for further medical care.