DIAGNOSTICS: NEW TECHNIQUE COULD MAKE PERSONALIZED MEDICINE AFFORDABLE

A team of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory has invented a technique in which DNA or RNA assays — the key to genetic profiling and disease detection — can be read and evaluated without the need of elaborate chemical labeling or sophisticated instrumentation. Based on electrostatic repulsion — in which objects with the same electrical charge repel one another — the technique is relatively simple and inexpensive to implement, and can be carried out in a matter of minutes. The researchers, in a paper published in the online edition of the journal Nature Biotechnology, describe how dispersing a fluid containing thousands of electrically-charged microscopic beads or spheres made of silica across the surface of a DNA microarray and then observing the movement of the spheres provides measurements of the electrical charges of the DNA molecules. These measurements can in turn be used to interrogate millions of DNA sequences at a time. These measurements can be observed and recorded with a simple hand-held imaging device — even a cell phone camera will do. Until now, the researchers said, the use of DNA microarray assays has been limited because current techniques typically depend upon fluorescence detection, a demanding methodology that requires time-consuming chemical labeling, high-power excitation sources, and sophisticated instrumentation for scanning. Such demands are generally well beyond the capabilities of individual laboratories or clinics, especially in developing countries.

 

Researchers at the Stanford University School of Medicine have identified a method that can predict with 70 percent accuracy whether a woman undergoing in vitro fertilization treatment will become pregnant. This information may someday help couples who want to undergo IVF and their doctors decide on their course of action, the researchers said. The new method involves using four factors to determine a woman's chance of becoming pregnant from an IVF cycle, the researchers reported in the journal open-access journal PLoS ONE. The four factors include the total number of embryos, number of eight-cell embryos, percentage of embryos that stopped dividing and would die, and the woman's follicle-stimulating hormone level – a measurement that estimates ovarian function – were most important in determining a woman's chance of becoming pregnant. The researchers also found that these four factors were more predictive than any single measure of an actual transferred embryo.

 

Scientists at the Burnham Institute for Medical Research in La Jolla, California have shown that neural stem cell development may be linked to Autism. The study, published in the Proceedings of the National Academy of Sciences, demonstrated that mice lacking the myocyte enhancer factor 2C (MEF2C) protein in neural stem cells had smaller brains, fewer nerve cells and showed behaviors similar to those seen in humans with a form of autism known as Rett Syndrome. The work represents the first direct link between a developmental disorder of neural stem cells and the subsequent onset of autism. MEF2C turns on specific genes that drive stem cells to become nerve cells. When MEF2C was deleted from neural stem cells in mice, there was a faulty distribution of neurons accompanied by severe developmental problems. Adult mice lacking MEF2C in their brains displayed abnormal anxiety-like behaviors, decreased cognitive function and marked paw clasping, a behavior which may be analogous to hand wringing, a notable feature in humans with Rett syndrome.

 

HEMATOLOGY: BAYER HEALTHCARE BUYS MAXYGEN’S HEMOPHILIA PROGRAM ASSETS FOR UP TO $120 MILLION
Bayer Healthcare said it is expanding its hemophilia portfolio with the acquisition of Redwood City, California based-Maxygen’s hemophilia program assets, including a next-generation recombinant Factor VIIa protein known as MAXY-VII. The lead therapeutic candidate is expected to enter human clinical testing in the third quarter of 2008. The total transaction is valued at $90 million upfront with a final, potential milestone payment of $30 million. Hemophilia is an inherited bleeding disorder caused by deficient or defective blood coagulation proteins. Roughly 20 to 30 percent of patients with hemophilia develop antibodies – or inhibitors – to current therapies. In these instances a Factor VIIa is used to bypass inhibitors and help these individuals to form clots. MAXY-VII is a next generation Factor VIIa clotting factor that may offer an improved dosing regimen and safety profile. Bayer believes the addition of the product could further build on its position in the market for hemophilia care. The company already markets a recombinant Factor VIII product known as Kogenate. Bayer also has ongoing clinical investigations to develop long-acting forms of Kogenate.

 

MIGRAINE: TORREYPINES THERAPEUTICS REPORTS POSITIVE MID-STAGE RESULTS
La Jolla, California-based TorreyPines Therapeutics said that data presented at the 50th Annual Scientific Meeting of the American Headache Society showed that, in addition to meeting the primary endpoint of headache pain relief at two hours, the company's lead experimental drug demonstrated improvement on important secondary endpoints in a mid-stage clinical trials. The drug, tezampanel demonstrated improvement in sustained headache response, absence of nausea or vomiting, absence of phonophobia and absence of photophobia. Tezampanel is the first AMPA/kainate-type glutamate receptor antagonist to be studied in clinical trials for chronic pain, including migraine. Glutamate receptors mediate the functioning of glutamate, an important excitatory neurotransmitter. While normal glutamate production is essential, excess glutamate production, either through injury or disease, can have a range of pathological effects.

 

HIV: STUDY SHOWS ZINC FINGER NUCLEASES USED TO GENERATE T CELLS RESISTANT TO VIRUS
Richmond, California-based Sangamo BioSciences said data demonstrating that human immune system cells (CD4 T-cells) can be made resistant to HIV infection by treatment with zinc finger DNA-binding protein nucleases or ZFN. The data suggest that the ZFN approach, which results in the permanent modification of the CCR5 gene encoding an important receptor for HIV infection, is a promising strategy for the treatment of HIV/AIDS. The work, conducted by researchers at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine in collaboration with Sangamo scientists, was published in an online edition of Nature Biotechnology. Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. Individuals carrying a naturally occurring mutation of their CCR5 gene, a variant known as CCR5-delta32, have been shown to be resistant to HIV infection.

 

STEM CELL RESEARCH: CIRM AWARDS $24 MILLION IN NEW GRANTS TO 25 INSTITUTIONS
The California Institute for Regenerative Medicine, the state’s stem cell agency, awarded a total of $24 million in grants under two separate programs. One set of 16 grants totaling $23 million will support research for the development of new lines of pluripotent human stem cells. The other will fund the planning stages of an innovative model for research teams that will collaborate on therapies for a specific disease or injury, the institute said. To ensure that research moves forward in all of the areas that have potential to deliver medical advances to patients, the institute said the grants will support research across the spectrum of approaches used to derive pluripotent stem cell lines, including the well-established means of human embryonic stem cells, which remain the gold standard for research into pluripotent cells, as well as new technologies such as iPS. The CIRM also awarded 22 grants totaling $1.1 million to support multi-disciplinary teams of scientists in pursuit of therapies for specific diseases. Stanford University and the University of California, San Francisco each received a total of five grants.

 

CML: SGX PHARMACEUTICALS SUBMITS APPLICATION TO FDA TO BEGIN CLINCIAL TRIALS
SGX Pharmaceuticals said that it has submitted an investigational new drug application to the U.S. Food and Drug Administration for SGX393. This compound is an internally developed, selective, orally-bioavailable small molecule for the treatment of relapsed and refractory chronic myelogenous leukemia. Gleevec, the standard of care for CML is a highly effective front-line therapy. But there are patients who relapse while on Gleevec, or who are intolerant to the therapy. In the majority of cases, relapses have been linked to the emergence of a number of drug-resistant mutant forms of the tyrosine kinase BCR-ABL. The single mutant that has been the most challenging to inhibit is the T315I mutant. SGX said neither Gleevec nor the two more recently approved CML treatments, Sprycel and Tasigna, inhibit the T315I mutant. SGX393 inhibits both wild-type BCR-ABL and many drug resistant mutant forms of BCR-ABL, including the T315I mutation.

 

CANCER: COMPOUND SELECTIVELY KILLS CANCER CELLS
Scientists at Stanford University have identified a molecule that uses this unexpected pathway to selectively kill cancer cells. In a study published in the journal Cancer Cell, the researchers said the finding could drive treatment strategies for cancer in an entirely new direction. Renal cell carcinoma, the most common form of kidney cancer, is nearly always caused by mutation of the von Hippel-Lindau tumor suppressor gene and often does not respond well to treatment. The researchers used a sophisticated screening procedure to search for molecules that could selectively destroy von Hippel-Lindau-deficient kidney cancer. The researchers discovered a compound, STF-62247, that was selectively toxic to renal cell carcinomas deficient in von Hippel-Lindau whereas cells with normal von Hippel-Lindau were not affected. Treatment of renal cell carcinoma cells lacking functional von Hippel-Lindau induced autophagy, a cellular recycling process that cells normally use to conserve resources during times of stress.

 

CLONING: MILL VALLEY COMPANY TO “REPLICATE” 9-11 HERO DOG

Mill Valley, California-based BioArts said it has selected Trakr, a German Shepherd that was among the first search and rescue teams to arrive at Ground Zero following the attacks of September 11, 2001, as the winner of its BioArts Golden Clone Giveaway contest. James Symington, a former police officer who now lives in Los Angeles with Trakr, submitted the winning essay. BioArts International, which is also holding an auction of five dog cloning slots from July 5th-9th, sponsored the Golden Clone Giveaway with the goal of identifying the world’s most “clone-worthy” dog and replicating it at no cost to its owner. Within 30 days, BioArts said it will transport a sample of Trakr’s DNA to the South Korean lab of their partner, the Sooam Biotech Research Foundation. BioArts International has been granted the sole, worldwide license for the cloning of dogs, cats and endangered species by Start Licensing, Inc. and applies to the SCNT cloning patents developed at the Roslin Institute for Dolly the sheep, the first successfully cloned adult mammal.