Paul O'Neill

New gene for juvenile polyposis

A team of oncologists has identified a new gene responsible for the onset of juvenile polyposis (JP), a condition affecting the colon and gastrointestinal tract, which significantly increases the risk of colorectal or stomach cancer in later life. James Howe and colleagues (University of Iowa, Iowa City, Iowa) studied four large families with histories of JP and by genetic linkage analysis narrowed down the gene search to a region on chromosome 10. The recent completion of the Human Genome Project allowed the group to identify candidate genes, and one of those, bone morphogenic protein receptor 1A, was discovered to be mutated in all the JP family members examined. Howe is now planning to create a mouse model of JP, which should be a valuable tool in the understanding of JP and in the testing of future therapies. The work was published in Junes Nature Genetics. PoN

Viral link to schizophrenia

Unexpectedly high levels of retroviral RNA have been detected in the cerebrospinal fluid of people suffering from schizophrenia, according to a recent study published in Proceedings of the National Academy of Sciences. Robert Yolken and colleagues (John Hopkins School of Medicine, Baltimore, MD, USA) also detected the viral RNA in samples taken from post-mortem brains of schizophrenic patients. Control samples from normal individuals contained no trace of the pathogen. The RNA detected was produced by HERV-W, an endogenous retrovirus. The authors speculate that re-activation of these latent components of the human genome might contribute to the pathology of schizophrenia. If this theory is proven, it could lead to new strategies for the treatment of this neurological condition. PoN

Heart dogma quashed

The widely accepted dogma that the human heart is intrinsically incapable of regeneration has been challenged by cardiologist Piero Anversa (New York Medical College, Valhalla, New York). Anversas team of researchers detected the presence of the cellular proliferation marker Ki-67 in samples of cardiac tissue taken from patients who had suffered a heart attack. These results, detailed in Junes New England Journal of Medicine, provide the strongest evidence to date for the existence of cardiac stem cells. If proven, the exciting possibility of promoting self-repair of damaged heart tissue via stem cell activation could be within reach. PoN

New use for measles vaccine

The virus used in the manufacture of the measles vaccine has been shown to be effective at destroying lymphoma cells in mice by researchers at the Mayo Clinic (Rochester, MN, USA). According to a report in the June edition of Blood, mice injected with human lymphoma cells develop tumours and these were seen to regress after injection with the Edmonston-B strain of the measles vaccine virus. Systemic viral injection also resulted in slowing of the progression of disease. Pilot studies are now underway to evaluate the effectiveness of this treatment in human lymphoma patients, potentially offering a vital alternative to existing therapies. PoN

Return of the leeches

The topical application of leeches has been shown to be highly effective at treating pain and inflammation in cases of osteoarthritis. The pilot study, published in Octobers edition of Annals of the Rheumatic Diseases, is the first to evaluate the beneficial effects of leeches in a clinical trial. sixteen patients with persistent knee pain caused by osteoarthritis were offered leech treatment in addition to conventional therapy. In those patients whom accepted, a remarkable improvement in pain relief was observed. The leech saliva contains an abundance of anaesthetic, analgesic, and histamine-like compounds which might be responsible for the observed effects. The team behind the study, working from the Essen–Mitte Clinic in Germany, advocate the initiation of a larger-scale, randomized clinical trial to evaluate fully the efficacy and safety of this treatment. PoN

3rd Human genome map published

The publication of a third version of the human genomic map has raised questions about the total number of genes present within our cells. The two earlier maps estimated the total gene number at around 35 000. The new study, published in Julys Genome Biology, identified twice as many genes. By comparing the draft sequence produced by the Human Genome Project with 13 different gene databases, an estimated 65 000–75 000 ‘transcriptional units’ were mapped, each unit being a strong contender for a gene. The analysis required vast computational power and was performed at the Ohio Supercomputing Centre (USA). The previous maps utilised only two such gene databases, resulting in a gene count that surprised many scientists. The maps authors, based at Ohio State University, believe their data will provide an invaluable tool in hastening the process of disease mapping and will support many years of intensive genetic research. PON

Promise for retinal gene therapy

The overgrowth of blood vessels in the eye, which can lead to blindness in patients suffering from macular degeneration or diabetic retinopathy, could be prevented by gene therapy, according to a study published in the Journal of Cellular Physiology. Lead author Peter Campochiaro (Johns Hopkins University School of Medicine, Baltimore, MD, USA), inserted the gene for pigment epithelium-derived factor (PEDF), a potent inhibitor of blood vessel formation, into the eyes of mice using a viral vector. The inserted gene was shown to be expressed in vivo, and was effective at inhibiting retinal neovascularization in three different mouse models of the human conditions. Current laser or surgical treatments do not remove the underlying stimulus for abnormal blood vessel formation in the retina, often resulting in re-growth of capillaries. Campochiaro believes his gene therapy approach will offer a longer-lasting alternative. PoN

Alzheimer's revival

The loss of cholinergic neurons seen in the forebrain of Alzheimers patients may be reversible, according to new research published in August in Proceedings of the National Academy of Sciences. Jonathon Cooper (Kings College, London) and colleagues injected nerve growth factor (NGF) into the ventricles of mice engineered to display Alzheimers-like symptoms. Surprisingly, NGF not only revived the morphology of the diseased neurons, but also restored cell numbers to original levels. It is thought that the cholinergic neurons affected – vital for memory and learning – do not die in the mice as the disease progresses, but switch to a dormant state. It remains to be seen whether human cells affected by Alzheimers can be similarly resurrected. PoN

Promising start for haemophilia gene trial

The first results in Junes New England Journal of Medicine from a recent clinical trial of a non-viral gene therapy for haemophilia indicate the treatment is beneficial and safe. The study, conducted by researchers from Beth Israel Deaconess Medical Center in Boston (MA, USA), involved inserting a factor VIII-expression plasmid into fibroblast cells isolated from the patient by electroporation. Once a factor VIII-expressing colony was obtained, the cells were injected back into the patients abdomen. Haemophilia is characterized by low levels of factor VIII in the blood, and even moderate increases in circulating concentration can make a large difference to quality of life. Of the six patients involved in the trial, four had elevated factor VIII levels, and none suffered any immune reaction to the treatment. PoN

Genetics infringes on pharmacology

The field of pharmacogenetics, which studies the interactions between genetic makeup and drug responses, offers prospects of gene-tailored drug prescriptions in the near future. One of the first studies in this field has determined that individuals homozygous for the D allele of angiotensin converting enzyme (ACE) benefit more from beta-blocker drugs than other ACE genotypes in cases of heart failure. Reported in the March issue of Circulation, these results are a first tentative step towards genetics influencing clinical decisions. PoN