Guidelines on cancer screening which were published nearly two years ago in the European Journal of Cancer called for population screening to be offered when shown to reduce disease-specific mortality or incidence and where it is clinically effective and cost effective. In spite of renewed pressure by European cancer experts, many of whom were involved in drawing up the guidelines, there has until now been no official validation of the recommendations. They are, however, to be included in the next update of "European Guidelines for Quality Assurance in Mammographic Screening."
The guidelines cover breast, cervical and colorectal cancer screening with X-ray mammography recommended every two to three years for all women in the 50 to 69 age group, with extension to the 40 to 49 age group if justifiable.
Although standard film/screen mammography systems still constitute the bulk of technology used in Europe, digital mammography systems are gradually making inroads because they eliminate the use of X-ray film and offer increased contrast resolution, a wider dynamic range, a higher signal-to-noise ratio and real-time image enhancement. Because of limitations on reimbursement and rigid budgetary pressures, however, many facilities will have to continue with non-digital systems.
Mirada Solutions (Oxford, England) is marketing computer-aided detection (CAD) technology for use with standard film/screen mammography units and which helps physicians to detect breast tumors at an earlier stage. The MicroDetect CAD image analysis software uses a conversion process that places the mammogram into a specific format – the standard mammogram form from which the software can precisely quantify microcalcifications – an early indicator of breast cancer.
MicroDetect CAD, which was developed by Professor Michael Brady and his group at Oxford University, is being commercialized by Mirada Solutions, a spin-out company from the university. The CAD technology analyzes the breast tissue images indicating visually the size and density of potential tumors in about one minute.
Dr. Ralph Highnam, CEO of Mirada Solutions, said that the MicroDetect technology can improve actual positive detection rates by 10% and reduce false positive signals by up to 40% compared to competitive systems.
The current software available for use with regular film/screen systems is presently being used by Oxford University and the Cancer Research Campaign (London). Clinical trials are under way at Churchill Hospital (also Oxford) and the Royal Free Hospital (London), with full U.S. clinical trials scheduled to begin early next year.
In addition, Mirada Solutions plans to launch new software for digital mammography use before the end of the year. The global X-ray mammography market is estimated to be worth about $330 million this year, growing at about 10% annually to reach $600 million by 2007.
Oral or inhaled insulin – the race to market
A number of companies are developing inhaled insulin delivery as a viable alternative to injection including Flamel (Lyon, France), Aradigm (Hayward, California), Aerogen (Sunnyvale, California) and Inhale Therapeutics (San Carlos, California), although there are concerns that the hormone may damage lung tissue.
Aradigm presented results at a recent diabetes meeting in England on a study of 17 asthmatic patients showing that the company's AERx iDMS electronic pulmonary insulin system could be a viable possibility for diabetes control in asthma sufferers. The results showed, however, that asthmatics absorbed less insulin compared to non-asthmatics, with a lower glucose-reducing effect. Per Clausen of Novo Nordisk (Copenhagen, Denmark), which is collaborating with Aradigm in development of the AERx iDMS technology, described the results as "promising news."
Aerogen reported at the same meeting preliminary Phase II trial results comparing its Aerodose insulin inhaler with injected insulin. In 15 Type 2 maturity onset diabetic patients, the amount of insulin absorbed using the Aerodose was equally "as consistent" between doses as absorption following injection. Peak insulin levels were attained more quickly with inhalation with no inhaler-related adverse effects reported. Aerogen has not yet announced an insulin marketing collaboration, but is expected to do so before year-end.
In the oral insulin sector, there are presently two main contenders: Emisphere (Tarrytown, New York) and Nobex Pharmaceuticals (Philadelphia, Pennsylvania). Nobex released preliminary but positive Phase II data for its oral insulin in June, while Emisphere has reported that three early-stage clinical trials have shown its oral insulin is safe and effective. Two oral formulations showed absorption in the gut and lowered blood glucose levels without apparent side effects. Emisphere's oral insulin has yet to be tested on diabetics, but if successful, it could be a blockbuster product.
A vaccine against Alzheimer's
In October, 375 patients diagnosed as sufferers of Alzheimer's disease received the first of a series of injections of a therapeutic vaccine with the aim of restoring levels of memory and lucidity. In France, 100 patients at the Salpetri re Hospital (Paris) and at university hospitals in Lille, Bordeaux, Montpellier and Toulouse are taking part in the trial, with additional centers in other European countries, the U.S. and Canada.
Alzheimer's disease has always been considered incurable, and the hopes encapsulated in these trials will be confirmed or lost by the end of the trials in 18 months time in 2003, although preliminary indications are expected by next spring. The eventual efficacity (or not) will be assessed by using a series of standard cognitive tests, and in the eventuality that there are positive results, the vaccine could become available in hospitals the same year. There are waiting lists for this vaccine therapy in many French hospitals.
There are two schools of thought regarding the causative factors of Alzheimer's disease. One group maintains that amyloid plaque deposits, formed by an abnormal accumulation of peptide A beta are guilty, while the other group considers that another protein, tau, which accumulates in degenerated neurones between the plaques, is responsible.
The vaccine in these trials, from Elan Pharmaceuticals (San Francisco, California), a subsidiary of Elan (Dublin, Ireland), has been developed by supporters of the first hypothesis. It is a synthetic protein developed from natural peptide A beta. When injected into mice, it induced the formation of antibodies which attach to the amyloid plaque and stimulate the glial cells which will eliminate the plaque. In 1999, a research group at Elan Pharmaceuticals, led by Dale Schenk, demonstrated that the vaccine stimulated the immune system of special transgenic mice to destroy the amyloid plaque. In the following year, the results were confirmed by groups at the University of Toronto (Toronto, Ontario) and Florida State University (Tallahassee, Florida). They confirmed the attenuation of the plaque deposits and also found the rodents regained normal functioning.
"This line of research seems very promising, but we cannot prove the efficacity of the vaccine until we have tested it in humans," said Peter Saint-George-Hyslop of the University of Toronto. Phase I trials have been successfully completed in Britain and the U.S. by Schenk's group at Elan, and the enlarged Phase II trials are to assess efficacy on a larger scale.
Dr. Andr Delacourte, research director of the laboratory of cerebral aging and neuronal degeneration at University Hospital (Lille, France), warned that the clinical signs of Alzheimer's disease only appear when the damage caused by protein tau reaches the cortex, the region of the brain responsible for cognitive activities. In this situation the positive action of the vaccine may only be limited. On the other hand, if peptide amyloid causes the tau pathology, there could be spectacularly effective results. We will have to wait results of the current trials to be sure.
Anti-nicotine vaccine starts trials
Xenova Group (London, England) reported the start of Phase I clinical trials on its TA-NIC therapeutic vaccine to assess safety, tolerance and immunogenicity of the vaccine both in smokers and non-smokers. The vaccine, which is administered intramuscularly by injection, is believed to be the first anti-nicotine addiction vaccine to enter clinical testing.
Currently available therapies for nicotine addiction include nicotine replacement therapy delivered by skin patch, chewing gum or inhaler, or treatment with the nicotine-free drug bupropion. TA-NIC uses a novel mode of action whereby it seeks to prevent nicotine from entering the brain.
According to World Health Organization (Geneva, Switzerland) estimates, over 1 billion people worldwide smoke tobacco products, resulting in around 3 million deaths a year from smoking-related diseases. In spite of the known health risks, many people wishing to give up smoking find it very difficult because of the addictive properties of nicotine and the unpleasant withdrawal symptoms. The Centers for Disease Control and Prevention (Atlanta, Georgia) estimates that 17 million smokers in the U.S. alone attempt to quit each year.
David Oxlade, Xenova's chief executive, said, "Most people who want to stop smoking find it very hard to do so, even though they may be aware of the risks involved. Although at an early stage of development, if TA-NIC can be of assistance it could have an important contribution to make in reducing the burdens that smoking imposes."
West Nile vaccine trials coming in 2002
Acambis (Cambridge, England) anticipates starting Phase I clinical trials of a prophylactic vaccine against West Nile virus next year. The program to develop a vaccine against the virus, which is carried by mosquitoes, is being funded by a $3 million grant from the U.S. National Institutes of Health (Bethesda, Maryland). The candidate vaccine, derived from the live attenuated 17D strain of yellow fever, has been developed using Acambis' ChimeriVax technology and has completed preclinical trials assessing its safety profile, immunogenicity and ability to protect against the West Nile virus.
Outbreaks of West Nile have been reported in Africa, the Middle East and Europe. The disease was reported for the first time in the U.S. in 1999 and has since spread to 21 states. Horses are highly susceptible to West Nile virus and Acambis is in discussions with several animal-health companies for the potential commercialization of a veterinary vaccine.
Acambis also has successfully completed a Phase II challenge trial with its Japanese encephalitis vaccine, ChimeriVax-JE, which the company said induced an immune response with long-term memory and a rapid rise in protective antibodies.
Smallpox vaccination guidance updated
The World Health Organization has reviewed guidelines on smallpox vaccination in the light of current worries that populations might be deliberately infected with the smallpox virus . The WHO Smallpox Advisory Group said in its review: "Existing vaccines have proven efficacy but also have a high incidence of adverse side-effects. The risk of adverse events is sufficiently high that mass vaccination is not warranted if there is no or little real risk of exposure. Individual countries that have reason to believe that their people face an increased risk of smallpox because of deliberate use of the virus are considering options for increasing their access to vaccines. The vaccines would be given to people who are at risk of exposure to smallpox, including health and civil workers, and would be used in a search and containment exercise should an outbreak occur."
Vaccination of entire populations is not recommended. The reasons for this are a risk of severe reactions to the vaccine, including death, and the fact that vaccination can prevent smallpox even after exposure to the virus. The WHO advisory group recommended that increased attention be given to the extent and quality of existing stocks and to the potential need to stimulate vaccine production and to increase emergency stock levels.
Longevity and genes
Ten years ago, France started an ambitious program of research that aimed to identify those genes associated with long life. Chronos, the resultant project, launched in 1991 at the Centre d'etudes du polymorphisme humain (CEPH; Paris), started the first bank of DNA samples from centenarians. In 1994 the researchers involved published in Nature Genetics results of a study showing a relationship between longevity and the presence of one of the genes associated with apolipoprotein E (Apo E). The DNA databank, which has continued to expand, is maintained by Genset (Evry, France), and now covers more than 900 very old people.
A recent publication in Proceedings of the National Academy of Sciences (PNAS) by Louis Kunkel and Thomas Perls of the Harvard Medical School (Boston, Massachusetts) compared DNA samples from 322 people of at least 98 years of age and with one or more brothers or sisters who lived to over 90. The research identified that the nonagenarians had in common one or more identical genes situated between markers D4S1572 and D4S406 on chromosome 4.
Gilles Thomas, director of CEPH, said, "We plan to publish in the near future a study similar to that of the Americans (at Harvard Medical School), but with a population sample much larger, of 900 people." It is likely that this study will focus on the role of ApoE and particularly on the interaction of the gene concerned with one or more environmental factors, according to Philippe Amougel, a geneticist at the INSERM laboratory to study the impact of interactions gene/environment on human health (Lille, France). He pointed out that the role of ApoE is closely involved with one's alimentary regime, so that for each gene implicated a therapeutic strategy needs to be established taking into account all factors, whether they be alimentary, stress factors or hormonal. "Improvements in hygiene and in work conditions have played a major part in the increase of life expectancy over the past 50 years. Human genetics, on the other hand, still have to establish their significance," Amougel said.
Antimalarials and CJD
Since August, 15 French patients suffering from Creutzfeldt-Jakob syndrome (CJD) have been following a new curative therapy. Stanley Prusiner and his group at the University of San Francisco have discovered a new property for quinacrine, a generic used in the treatment of malaria. The researchers had the idea of testing products known for their capacity to pass the blood/brain barrier. They found that quinacrine, which falls into this group of products, also destroyed in vitro cells infected by the pathogenic form of the prion protein. It is possible that the treatment could also be used in the human form of mad cow disease (vCJD, or variant Creutzfeldt-Jakob disease).
"The results of this therapy method will not be known for several weeks or several months," said Annick Alp rvitch, director of the French system of epidemic surveillance of CJD. If quinacrine proves to be effective, other prion diseases such as fatal familial insomnia or Gerstmann-Straussler-Scheinker syndrome (problems of coordination of movements) could also benefit.
NHS to modernize maternity services
The British government has allocated an additional $145 million to the National Health Service (NHS) for improvements to 209 maternity units in England. This will include 93 major refurbishing projects and the updating of 65 antenatal clinics. The NHS also plans to recruit 2000 additional midwives over the next five years and to impose new national standards so as to reduce what are accepted as excessive national variations in the quality of antenatal, maternity and postnatal care.