Adam Rutherford

Eyeing-up stem cell transplantation

The recent identification of neural stem cells has encouraged scientists that these undifferentiated progenitor cells might hold the key to treatment of many neuro-degenerative disorders. This possibility took a step forward when researchers led by Don Sakaguchi (Iowa State University, IA) and Michael Young Harvard Medical School, MA, USA) successfully transplanted and integrated stem cells into the eyes of postnatal Brazillian opossums. Spheres of green-fluorescent protein (GFP) expressing rat hippocampal-derived or embryonic mouse stem cells were injected into the eyes of opossum pups. Immunoreactivity for several neural and retinal markers was observed, indicating that these transplanted cells had integrated into the eye and differentiated into retinal neurons. Integration and survival of these cells raises the prospect of treatment for human retinopathies such as glaucoma and macular degeneration. (AR)

34 m for juvenile diabetes

The largest ever statistical study of the genetics of type 1 diabetes has been funded by the Wellcome Trust (London, UK) and the Juvenile Diabetes Research Foundation. Over the course of five years, a

A gene for Alexander disease

34 (£20) million grant will be used to identify the genes involved in juvenile onset (insulin dependent) diabetes, using 10 000 diabetic and 10 000 healthy subjects. The research, which will be based at the Wellcome Trust Centre for Molecular Mechanisms in Disease (University of Cambridge, UK), will also incorporate analysis of non-obese diabetic (NOD) mice. This follows on from a recently published Korean–Canadian study, in which juvenile diabetes was eliminated in NOD mice by insulin gene therapy. Ahyun Chul Lee and colleagues (Yonsei University Medical School, Seoul, South Korea) used a recombinant adeno-associated virus that expressed an insulin analogue, and prompted long-term remission from diabetes. These data hold great promise for treatment in humans, which currently requires several insulin injections per day. AR

Leukemia cells fall on their swords

The genetic cause of a mercifully rare, but devastating childhood condition – Alexander disease – has been determined. The symptoms of the disease, which is normally fatal before the age of 10, includes psychomotor retardation and spasticity, and the formation of pathological fibers – called Rosenthal fibers – in astrocytes. Having previously identified these fibers in transgenic mice that overexpress the widely studied astrocyte marker gene glial fibrillary acidic protein (GFAP), Albee Messing and colleagues (University of Wisconsin, WI, USA) have identified de novo GFAP point mutations in 11 postmortem Alexander disease patients. Interestingly, all of the mutations predict non-conservative alterations of an arginine residue. These data indicate that Alexander disease is the first example of a primary genetic disorder of astrocytes – one of the major cell types of the CNS. AR

Cancer Research UK looks to NCI forsuccess

Researchers from the University of California at San Diego (CA, USA) have designed a strategy to treat leukemia by inducing transformed cells to kill themselves. Paolo Vigneri and Jean Wang found that the drug STI571 stimulated nuclear entry for the otherwise cytoplasm-bound chimeric oncoprotein BCR–ABL, a molecular hallmark of chronic myelogenous leukemia (CML) caused by an in-frame translocation. In the cytoplasm BCR–ABL activates mitogenic and anti-apoptotic pathways, and thus causes cancer. However when imported into the nucleus, it was found to induce cell death. The effect of STI571 was found to be reversible, but used in conjunction with leptomycin B – a drug that prevents nuclear export of proteins – selectively killed bone marrow cells that express BCR–ABL. This technique, which converts the leukemia-causing protein into a weapon of its own destruction, could prove to be a valuable tool for the treatment of CML. AR

Gene therapy for the head and neck

This month sees the merging of the UKs two largest cancer research charities to form a national organization that will include some inspiration from across the Atlantic.

Nobel prizes to cancer biologists

WENDEL Yarbrough and colleagues (University of North Carolina at Chapel Hill, NC, USA) have made advances towards the treatment of head and neck cancer. 3-D cell-culture models that imitate the real structure of head and neck epithelium were used as recipients of adenovirus-mediated gene delivery. Epithelial cells in a monolayer were easy to infect due to the presence of the human coxsackie and adenovirus receptor (hCAR). However, the group noted that expression of hCAR was most prevalent in undifferentiated dividing cells, particularly oropharyngeal tumor cells. This raises the prospect of adenoviral gene delivery to these tumor sites without affecting surrounding non-cancerous cells. Furthermore, such a system may prove useful in treating severe cellular dysplasia, a precancerous condition in which hCAR expression is maintained. Yarbrough commented, ‘theoretically, in people at high risk for cancer, adenoviral gene therapy would only infect the precancerous sites and leave the normal, well differentiated sites alone’. (AR).

Stemming stroke-damaged brains

The most prestigious prize in biomedical research has gone to three researchers studying the molecules involved in cell cycling and cancer. Sir Paul Nurse, Tim Hunt (Imperial Cancer Research Fund, London, UK) and Leland Hartwell (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) will share the

Night owls and morning larks

1 million Nobel Prize for Medicine, despite Nurses claim in 1992 that owing to governmental cutbacks, Britain would suffer a dearth of Nobel laureates. Over the last 30years, the three scientists have discovered and characterized key regulators of the cell cycle, including the cyclin and CDC genes, and demonstrated their cross-species significance and roles in the uncontrolled cell divisions seen in cancer. AR

Looking into mirror movement disorder

Stem cells could be the building blocks to reconstruct damaged areas of the brain following strokes, according to research reported at the American Stroke Associations (ASA) 26th International Stroke Conference. A team of researchers, led by Daniel Rosenbaum, implanted rat stem cells into adult rat brains that had suffered stroke damage. ‘We were not sure the transplanted cells would even survive,’ comments Rosenbaum, ‘but they did, in both normal and stroke-damaged brains. In just seven days some cells had begun to differentiate into the basic, yet immature types of cell that form the fundamental structure of the brain.’ These data – which further refutes the old dogma that neurons are ‘hard-wired’ – showed that the newly implanted stem cells formed axonal connections with neighboring cells, and induced the formation of blood vessels to nourish them, indicating a potential treatment for stroke victims in the future. Guarav Gupta was awarded the Young Investigator of the Year by the ASA for his contribution to this work. AR