Photo taken from one of Target Health Inc’s 24th floor corner offices.
Wishes You a Happy Hanukkah and a Merry Xmas in 2 0 1 1
Improving BP in Middle Age Pays Off Later
December 22, 2011, by Reed Miller (Chicago, IL) — Lowering blood pressure during middle age reduces the lifetime risk of cardiovascular events, a new analysis of data pooled from seven cohort study shows .
“Avoiding hypertension before middle age and delaying the onset of the development of hypertension both appear to have a significant impact on an individual’s remaining lifetime risk for cardiovascular disease,” study authors Dr Norrina Allen (Northwestern University, Chicago, IL) and colleagues explain in their report, published online December 19, 2011 in Circulation.
Allen et al analyzed data from 61 585 patients in seven diverse US cohort studies in the Cardiovascular Lifetime Risk Pooling Project to see how changes in blood pressure during middle age can affect lifetime risk of cardiovascular disease, coronary disease, and stroke after age 45. Each patient was followed for an average of 14 years and a total of 700 000 person-years.
Categorized by their BP at the age of 55, 25.7% of men and 40.8% of women had normal blood pressure; 49.4% of men and 47.5% of women had prehypertension; 18.1% of men and 9.6% of women had stage 1 hypertension; and 6.8% of men and 2.2% of women had stage 2 or treated hypertension. About half of the subjects stayed in the same BP category from age 41 to 55, while 30% of men and 40% of women increased their blood pressure before they were 55.
Study subjects who maintained or decreased their blood pressure to normal levels ( < 120/80 mm Hg) by the time they were 55 had the lowest remaining lifetime risk of cardiovascular disease of 22% to 41%, while people who developed hypertension by age 55 had a 42% to 69% lifetime risk.
The patients who improved their BP may have changed their diet and exercise habits, or the difference may have just been regression to the mean. Regardless, the worst lifetime risk of disease was seen in men who developed hypertension during middle age, while in women, the subjects who had hypertension from age 41 through 55 years of age had the worst lifetime risk. “Although it was not consistently evident that a longer duration of high BP was associated with increased lifetime risks, it is possible that a greater duration of hypertension is associated with increased competing risk from non-CVD mortality,” the authors state.
“Taking BP changes into account can provide more accurate estimates for lifetime risk for CVD and represent a step forward in developing individualized risk-prediction strategies,” Allen et al conclude.
The authors report that they have no disclosures.
A Reading of 110 Over 70 or 75 is Normal
Blood Signature May Predict Alzheimer’s Disease
December 22, 2011, by Deborah Brauser — A molecular signature found in serum samples may predict future development of Alzheimer’s disease (AD), even before the first symptoms of the disease occur in patients, new research suggests.
In a cohort study of more than 100 elderly patients with mild cognitive impairment (MCI), investigators found that those who progressed to AD less than 4 years later had a molecular signature suggesting a state of increased hypoxia.
“The study is important, as it identifies molecular changes associated with AD progression years in advance,” lead author Matej Orešič, PhD, research professor of systems biology and bioinformatics at the VTT Technical Research Center of Finland in Espoo, told Medscape Medical News.
“The study therefore suggests that a blood test may eventually be available to identify the patients at risk of AD who could then be followed-up more tightly,” said Dr. Orešič.
The investigators note that the application of a simple biochemical assay from these blood tests could complement neurocognitive assessments given to elderly patients.
“Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues,” they write.
The study was published online December 13 in Translational Psychiatry.
Small Molecules as Predictors?
MCI is considered a transitional phase between normal aging and AD.
“MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition,” the investigators write.
Dr. Orešič reported that he has been investigating metabolome (the complete set of small-molecule metabolites) in relation to health and disease for nearly 10 years, with lipids being one of his main areas of study.
“Lipids are known to play an important role in AD pathogenesis, but it has not yet been known whether lipids or any other small molecules can also be good predictive markers of AD,” he explained.
For this study, the investigators used metabolomics, a method of detecting small metabolites, to produce blood profiles associated with the progression of AD.
They evaluated information on 143 patients diagnosed with MCI from longitudinal databases and then compared their findings to data from 46 healthy control volunteers and 37 patients with AD.
Blood samples were collected at baseline (time of diagnosis or upon identification as healthy control participants) and during a follow-up period, the average of which was 27 months (±18 months).
Hypoxia May “Kick Off” AD
Results showed that 52 of the patients with MCI progressed to AD by the end of the follow-up period.
“At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins, and sterols,” write the investigators.
Although 3 metabolites were identified in the molecular signature of the MCI patients who progressed to AD, “the main contributor to the predictive model” was 2,4-dihydroxybutanoic acid (P = .0048). This indicated the potential involvement of hypoxia.
Analysis of metabolic pathways showed that upregulation of the pentose phosphate pathway was associated with AD progression; this also implicated hypoxia, along with oxidative stress, as having a role in early disease process.
Dr. Orešič noted that there were two surprising aspects to the study. First, although past research has shown that several membrane phospholipids, as measured in blood, were diminished in patients with AD, “these lipids were not early predictors of AD in our study.”
Instead, “the lipid-specific changes may be a later event in AD pathogenesis,” he said.
“Second, instead of lipids, we observed metabolic changes associated with hypoxia as early predictor of AD, suggesting that hypoxia may be an early event kicking off the AD.”
Dr. Orešič reported that the investigators are now “aiming to validate our findings” in a large prospective cohort. In addition, they are striving to better understand the physiological origin of the molecular changes observed in the blood.
“For this reason, we are currently undergoing detailed metabolomics analyses of cerebrospinal fluid samples from the same patients. Further related studies in this direction are also being considered.”
The study was supported under the 7th Framework Program by the European Commission and by grants from the Health Research Council of The Academy of Finland and from Kuopio University Hospital. Dr. Orešič has disclosed no relevant financial relationships.
Transl Psychiatry. Published online December 13, 2011
Gotthard Base Tunnel
PopSci.com, December 22, 2011 — The Swiss have solved one of Europe’s great problems: The Alps make shipping freight expensive. A decade ago, miners began digging outward from two 2,600-foot vertical shafts in Sedrun, Switzerland. They’ve since moved 31 million tons of rock to connect Italy to Germany via high-speed rail through the world’s longest train tunnel, 35.4 miles long. Manufacturer Herrenknecht built four 3,000-ton boring machines for the project, and after one of them encountered a zone of dangerous soft rock, crews began using a unique system of deformable steel rings to hold the tunnel open. The Gotthard will double freight capacity through one of Europe’s most vital trade corridors and will cut an hour from the four-hour trip between Zurich and Milan.
Target Health Inc. 23rd Floor
Target Health Inc. on left: 23rd Floor Conference Room. Behind the Tree is the IT Department and a Kitchen. Other side of the floor is the Statistics Dept and Systems Administrators
Target Health Inc. 24th Floor
Decorations in the Large Reception Area. To the left, conference room and clinical offices. To the right, Quality and Clinical Offices and Kitchen
Holiday Decorations on the 24th Floor at Target Health Inc. Target Health Inc. 23rd Floor has the same decorations
A Wristwatch that Monitors Blood Pressure
This wireless monitor from Healthstats detects blood pressure by detecting the shape of a pressure wave as blood flows through an artery.
Researchers hope a device that tracks vital signs around the clock will help patients better control their blood pressure.
MIT Technology Review, by Emily Singer — Although high blood pressure can be monitored, and treated effectively, with a number of drugs, a quarter of the people with the condition don’t even know they have it, according to the American Heart Association. Of those who know they have high blood pressure, only two-thirds get treatment, and fewer than half have it under control.
Now a new wireless monitor from Hewlett-Packard and a Singapore company called Healthstats aims to make it much easier for patients and doctors to monitor blood pressure. The device, which has the size and look of a wristwatch, can monitor pressure continuously—which provides a much more accurate picture than infrequent readings in the doctor’s office. Until now, the only way to do such continuous monitoring has been with a cumbersome inflatable cuff for the arm or wrist.
The new monitor comes with related software designed to keep patients and doctors informed of the wearer’s vital signs, including blood pressure. Data is transmitted from the device to the user’s cell phone, and then to the cloud, where clinicians can review it. Patients and their doctors can view 24-hour graphs of blood pressure, and the system can sound alerts when it detects abnormalities in pressure or other measures.
The research is part of a growing effort to use wireless monitors to capture round-the-clock medical data outside of the hospital. Physicians hope such devices will inspire patients to better monitor their own health, and help uncover difficult-to-diagnose conditions, such as nighttime hypertension.
Unlike standard equipment, the Healthstats device relies on a sensor that rests against an artery in the wrist and detects the shape of the pressure wave as blood flows through it. (The device is first calibrated with a standard blood pressure monitor.) “Together with algorithms we have developed, the indices can be processed to get heart rate, diastolic and systolic pressure, and other measures,” says Ting Choon Meng, a physician and Healthstats CEO.
A wired version of the Healthstats monitor is currently in use in hospitals in Singapore and other parts of the world. The company began developing its wireless version about a year ago, in collaboration with HP, which has developed a software platform that can be paired with this and other wireless monitors.
“We have developed an application for a patient and physician portal where all this information will be delivered to the appropriate person,” says Lloyd Oki, vice president of Asia Pacific sales, communications, and media solutions at HP. “It could be an adult buying a mobile monitoring device for their parents, or a younger person being monitored, with the information sent to a clinician or adult caregiver.” Such devices might also be of interest to professional athletes, he says, perhaps calling attention to seemingly healthy athletes with undetected heart issues.
One issue still to be answered is how accurate the device is at measuring blood pressure when people are moving around. Healthstats has shown that the monitor works as well as other measures when users are sitting still, but has yet to publish comparable results for people in motion. “The bottom line from my standpoint is that it is a great idea that still needs to be fine-tuned to be usable in ambulatory patients,” says Dena Rifkin, a physician and assistant professor of nephrology at the University of California, San Diego.
A clinical trial underway in Singapore is designed to assess how the device affects patient and physician behavior, rather than its accuracy. A hundred patients, some healthy and some with a high risk of chronic illness or a history of strokes, will use the device over eight weeks. “Every morning, they will receive a summary of the findings via SMS,” says Ting. “A call center will look at data round the clock and intervene if needed.”
Researchers will then determine whether the monitor helped people with hypertension better control it, and whether it could detect abnormal blood pressure in people who were seemingly healthy. As more people measure their blood pressure throughout the day and night, physicians are discovering different patterns of abnormal blood pressure, such as hypertension only at night, or blood pressure spikes in the early morning, which may contribute to the high percentage of strokes that occur early in the morning, says Ting.
A Nightshirt to Monitor Sleep
Sweet dreams: The Somnus sleep shirt has embedded fabric electronics to monitor respiration. Nyx Devices
A newly developed smart shirt detects the wearer’s stage of sleep via respiration patterns.
MIT Technology Review, by Emily Singer — What if your pajamas could tell you how well you slept? That’s the dream of startup Nyx Devices, which has developed a nightshirt embedded with fabric electronics to monitor the wearer’s breathing patterns. A small chip worn in a pocket of the shirt processes that data to determine the phase of sleep, such as REM sleep (when we dream), light sleep, or deep sleep.
“It has no adhesive and doesn’t need any special setup to wear,” says Matt Bianchi, a sleep neurologist at Massachusetts General Hospital and co-inventor of the shirt with Carson Darling, Pablo Bello, and Thomas Lipoma. “It’s very easy—you just slip it on at night,” says Bianchi, who has no formal role with Nyx Devices.
When people with sleep disorders spend the night in a sleep lab, they are hooked up to a complex array of sensors that monitor brain activity, muscle activity, eye movement, and heart and breathing rate. Nyx’s Somnus shirt dramatically simplifies this by focusing only on respiration. “It turns out that you can tell if someone is awake or asleep and which stage of sleep they are in purely based on breathing pattern,” says Bianchi. “That’s a much easier signal to analyze than electrical activity from the brain.”
During REM sleep, the respiratory pattern is irregular, with differences in the size of breaths and the spacing between them. Breathing during deep sleep follows an ordered pattern, “like a sine wave,” says Bianchi. “And the breath-to-breath differences are very small.” The lighter stages of non-REM sleep fall somewhere in between. “The motivation behind the shirt is to allow repeated measurements over time in the home,” he adds. Users can log their habits, such as coffee or alcohol intake, exercise, or stress, and look for patterns in how those variables affect their quality of sleep.
Analyzing sleep stages based on respiration is still considered experimental. But Bianchi is now testing the device on patients who come to his sleep clinic who are also assessed using standard technology, known as polysomnography. The team will soon begin home tests of the shirts to further validate its use outside of the lab. The company hopes to have a commercial product available by summer of 2012 for less than $100.
The shirt is part of a growing number of devices that people can use to monitor sleep at home. The simplest, including an iPhone app, use accelerometers to measure movement, giving a rough gauge of when people fall asleep and wake up. A more sophisticated consumer device that monitors electrical activity from the brain and muscles, called the Zeo, came on the market two years ago.
While Nyx envisions the shirt as a consumer product, Bianchi wants to use it for his patients. Bianchi’s previous research has shown that people with insomnia often underestimate how much they sleep, so he wants to determine whether giving them an objective way to measure sleep will help them reassess their condition and improve quality of sleep. “It will be a game changer for my clinical practice,” he says. “There are zero objective tools available to physicians to assess insomnia.”
Holiday Wishes 2011 and Happy New Year 2012
All of us at Target Health Inc. wish our 4,000-plus loyal readers of OnTARGET from all around the world, HOLIDAY GREETINGS and HAPPY NEW YEAR.
ON TARGET will take a vacation till after the New Year.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
Two New Disinfection Techniques May Revolutionize Hospital Room Cleaning
A new technology known as HINS-light decontaminates the air and exposed surfaces by bathing them in a narrow spectrum of visible-light wavelengths. (Credit: Image courtesy of University of Strathclyde)
A pioneering lighting system that can kill hospital superbugs, including MRSA and C.1) ___, has been developed by researchers at the University of Strathclyde in Glasgow, Scotland. The technology decontaminates the air and exposed surfaces by bathing them in a narrow spectrum of visible-light wavelengths, known as HINS-light. Clinical trials at Glasgow Royal Infirmary have shown that the HINS-light Environmental Decontamination System provides significantly greater reductions of bacterial pathogens in the hospital environment than can be achieved by cleaning and disinfection alone, providing a huge step forward in hospitals’ ability to prevent the spread of 2) ___. According to the researchers, “The technology kills pathogens but is harmless to 3) ___ and staff, which means for the first time, hospitals can continuously disinfect wards and isolation rooms.
The system works by using a narrow spectrum of visible-light wavelengths to excite molecules contained within bacteria. This in turn produces highly reactive chemical species that are lethal to bacteria such as methicillin-resistant Staphylococcus aureus, or 4) ___, and Clostridium difficile, known as C.diff. The clinical trials have shown that the technology can help prevent the environmental transmission of pathogens and thereby increase patient safety.
The technology uses HINS-light which has a violet hue, but the research team has used a combination of LED technologies to produce a warm white lighting system that can be used alongside normal hospital lighting. Decontamination methods involving gas sterilants or UV-light can be hazardous to staff and patients, while cleaning, disinfection and hand washing, although essential routine procedures, have limited effectiveness and problems with compliance. HINS-light is a safe treatment that can be easily automated to provide continuous disinfection of wards and other areas of the clinical environment. The pervasive nature of 5) ___ permits the treatment of air and all visible surfaces, regardless of accessibility, either through direct or reflected exposure to HINS-light within the treated environment.
The technology was developed in Strathclyde’s pioneering Robertson Trust Laboratory for Electronic Sterilization Technologies (ROLEST), which is dedicated to controlling infection in today’s healthcare environments.
“This is the future, because many hospital 6) ___ are preventable with better cleaning methods,” says Dick Zoutman, who is also Quinte Health Care’s new Chief of Staff. “It has been reported that more than 100,000 people in North America die every year due to hospital acquired infections at a cost of $30 billion. That’s 100,000 people every year who are dying from largely preventable infections.” Dr. Zoutman has also used this disinfection technology to kill bed 7) ___. A major U.S. hotel chain has already expressed interest in the technology because of its potential to save the company millions of dollars in lost revenue and infected furniture.
Dr. Zoutman worked in collaboration with Dr. Michael Shannon of Medizone International at laboratories located in Innovation Park, Queen’s University. Medizone is commercializing the technology and the first deliveries are scheduled for the first quarter of 2012. The new technology involves pumping a Medizone-specific ozone and hydrogen 8) ___ vapor gas mixture into a room to completely sterilize everything – including floors, walls, drapes, mattresses, chairs and other surfaces. It is far more effective in killing bacteria than wiping down a room. Dr. Zoutman says the technique is similar to what we now know Mother Nature uses to kill 9) ___ in humans. When an antibody attacks a germ, it generates ozone and a minute amount of hydrogen peroxide producing a new highly reactive compound that is profoundly lethal against bacteria, viruses and mold.
“It works well for Mother Nature and is working very well for us,” says Dr. Zoutman.
There are other disinfecting technologies that involve pumping gas into a room, but Medizone’s method is the only one that sterilizes as well as surgical instrument cleaning. It also leaves a pleasant smell and doesn’t affect any medical equipment in the room. The entire disinfection process is also faster than other methods — it takes less than one hour. Dr. Zoutman says the technology could also be used in food preparation areas and processing plants after outbreaks such as listeria and to 10) ___ cruise ships after an infection outbreak. Study results on the process are published in the December issue of the American Journal of Infection Control.
ANSWERS: 1) difficile; 2) infection; 3) patients; 4) MRSA; 5) light; 6) deaths; 7) bugs; 8) peroxide; 9) bacteria; 10) disinfect
Scientists Solve Puzzle of Black Death’s DNA
A draft sequence of the Yersinia pestis genome has been
reconstructed using DNA extracted from victims of the Black
Death. Source: Museum of London
Advancing science: the remains of plague victims in a 14th-century London cemetery. Source: Museum of London
After the Black Death reached London in 1348, about 2,400 people were buried in East Smithfield, near the Tower of London, in a cemetery that had been prepared for the plague’s arrival. From the teeth of four of those victims, researchers have now reconstructed the full DNA of a microbe that within five years decimated one-third to one-half of the population of Western Europe. The bacterium that causes plague, Yersinia pestis, is still highly virulent today but has different symptoms, leading some historians to doubt that it was the agent of the Black Death.
Those doubts were laid to rest last year by analysis of the bacterium’s DNA in plague victims from mass graves across Europe. With the full genome now in hand, the researchers hope to recreate the microbe itself so as to understand what made the Black Death outbreak so deadly. So far, the evidence points more toward the conditions of the time than to properties of the bacterium itself. The genome recovered from the East Smithfield victims is remarkably similar to that of the present-day bacterium, says the research team, led by Kirsten I. Bos of McMaster University in Ontario and Johannes Krause of the University of Tubingen in Germany.
This is the first time the genome of an ancient pathogen has been reconstructed, opening the way to tracking other ancient epidemics and how their microbes adapted to human hosts. The bacterium’s genome consists of a single chromosome, about 4.6 million DNA units long, and three small rings of DNA called plasmids. In the 660 years since the Black Death struck, only 97 of these December 2012). Dr. Krause and others reported the DNA sequence of one of the plasmids in August. The changes in the genome will be studied one by one to see how each affects the microbe’s virulence. The researchers hope eventually to modify a living plague bacterium so that its genome is identical to that of the agent of the Black Death. Such a microbe could be handled only in special secure facilities.
If the microbe’s genome is so little changed, the deadliness of the Black Death may reflect the condition of its medieval victims. The climate was cooling, heavy rains rotted out crops and caused frequent famines, and the Hundred Years’ War began in 1337. People were probably already suffering from malnutrition and other diseases when the plague arrived like the fourth horseman of the apocalypse.
Recovery of the medieval plague bacterium’s full genome is a technical tour de force. The DNA had been degraded into millions of small fragments that were overwhelmed in number by DNA from the human host and from the bacteria that consumed the body after death. Dr. Krause’s team fished out the plague DNA by using DNA from the modern bacterium, relying on the fact that DNA strands bind to DNA of complementary sequence. “This is a major technological step forward, a great advance for the entire field of DNA and pathogens,“ said Mark Achtman, an expert on ancient plague at University College Cork in Ireland. But Dr. Achtman disagreed with one issue in Dr. Krause’s findings, that of whether Yersinia pestis also caused the outbreak in the sixth century known as the Justinian plague. When the full genome of the medieval bacterium is compared with DNA recovered from other known human outbreaks, a tree of descent can be constructed. The Black Death genome lies so close to the root of the tree that the human pathogen probably did not exist much earlier or, if it did, has vanished without any descendants, Dr. Krause’s team says. This implies that the Justinian plague was caused by some other agent. Dr. Achtman said this conclusion was incorrect because the Krause team had omitted DNA from several human cases that place the root of the tree much further back in time. Dr. Krause said he had left these cases out because they seemed unreliable.
The modern plague bacterium changes its DNA units slowly, but it does quite often rearrange the order of its genes. Some experts believe gene order can affect pathogenicity. Dr. Krause had available only tiny fragments of DNA, so although he was able to reconstruct all the medieval bacterium’s genes he could not establish the exact order in which the genes were arranged, leaving open the possibility that the bacterium was inherently more pathogenic because its genome was differently organized. Paul Keim, an expert on infectious bacteria at Northern Arizona University, said that work by Dr. Achtman and Dr. Krause had shown that the Black Death “was really a series of epidemics coming out of China and sweeping across the susceptible ecological situation“ created by the culture of medieval Europe. The plague in each outbreak probably did not persist very long and was repeatedly re-established by new infections from East Asia, where the bacterium is still endemic in small rodents like marmots. “We don’t have a human ecological situation comparable today, plus it is really easy to break the transmission cycle with antibiotics and public health,“ Dr. Keim said. There are still small outbreaks, like one in Madagascar in the 1990s, but “a multiyear large human outbreak is inconceivable in this day,“ he said.
Besides the Justinian plague and the Black Death, a third great wave of plague swept out of China in 1894, causing an epidemic in San Francisco in 1900 and killing millions of people in India.
All the teeth used in the study will be returned to the skulls from which they were taken, now in a London museum whose archaeologists excavated the East Smithfield cemetery in the 1980s. Source: NYTimes, Fall 2011, by Nicholas Wade
Gene Therapy Helps Patients with Hemophilia B
Hemophilia B is less common than hemophilia A, a deficiency of clotting factor VIII. About 1 in 5 hemophilia patients has hemophilia B, while the other four have hemophilia A. Hemophilia is an inherited condition that affects men more frequently. Worldwide, about 1 in 5,000 men are born with hemophilia A and 1 in 25,000 men are born with hemophilia B each year. People with hemophilia bleed more following trauma than people without the disease, and those with severe disease may bleed spontaneously. Hemophilia B patients are unable to produce enough human clotting factor IX, also referred to as FIX, which is essential for normal blood clotting. Liver cells are the only cells in the body capable of producing a form of factor IX that is active in the clotting process.
According to an article published online in the New England Journal of Medicine (10 December 2011), an experimental gene therapy technique has been shown to boost the production of a vital blood clotting factor in six people with hemophilia B. As a result the therapy could give patients a long-term solution for preventing prolonged bleeding episodes and spontaneous bleeding.
“Hemophilia has long been one of the disorders thought most likely to be correctible with gene therapy, but previous approaches to deliver the gene have been disappointing. Results from this study represent a promising step toward making gene therapy a viable treatment option for hemophilia B,” said Susan B. Shurin, M.D., acting director of the NIH’s National Heart, Lung, and Blood Institute (NHLBI),. “If future studies support these findings, it would bring a significant improvement in the quality of life for those living with the disease.”
In preparation for the clinical trial, the FIX gene was packaged in a modified adeno-associated virus, AAV8, which targets liver cells. This potentially allowed the normal FIX gene to be delivered using intravenous infusion to the liver cells which should allow the patients to produce more FIX. The clinical trial then evaluated six people with severe hemophilia B who were producing clotting factor IX at less than 1% of normal levels before receiving the gene therapy. Prior to enrolling in the study, participants were receiving the standard treatment for severe hemophilia B of infusions of manufactured FIX several times a month.
Results showed that after receiving the FIX gene therapy, each study subject produced FIX at between 2 and 11% of normal levels. In the short-term follow-up period (six to 16 months), four of the six participants no longer required FIX infusions for routine bleeding. The other two participants required FIX infusions less frequently than before the study.
According to the authors, the unique feature of this approach is the use of AAV8 to deliver the gene to the appropriate cells, and if future studies show that immunologic or other factors do not limit its long-term effectiveness, people with hemophilia B could produce their own FIX and potentially avoid reliance upon FIX infusions. While more work is needed, these results are more promising than prior attempts at gene therapy for the hemophilias.
People with a Form of Muscular Dystrophy May Have Elevated Cancer Risk
Myotonic muscular dystrophy (MMD) is part of a group of inherited disorders and the most common form of muscular dystrophy in adults. There are two main types of MMD, type 1 and type 2, which are caused by mutations in two different genes. In both cases, the mutation is a result of greater than normal repetition of part of the gene along a segment of DNA. Repetition of parts of genes is common but, in these cases, the repeat length is so excessive that it disrupts normal gene function. Doctors who treat MMD patients occasionally observe the development of benign and malignant tumors. However, it has not been clear whether these cancers were part of the myotonic dystrophy syndrome or just a coincidence.
According to a study published online in the Journal of the American Medical Association (14 December 2100), adults with MMD may be at increased risk of developing cancer. The authors suggest that some of the genetic changes that lead to MMD may also be responsible for the observed increase in cancer risk, but more research is needed to confirm this hypothesis.
To determine if MMD patients were at higher risk of cancer than the general population, the authors identified 1,658 Scandinavian patients with MMD who were reported to the Swedish Inpatient Hospital Discharge Register from 1987 through 2004 or the Danish National Patient Discharge Registry between 1977 and 2008. The researchers then linked the patients to the corresponding cancer registry in Sweden and Denmark.
In the study, the investigators describe risks of all cancers combined and by cancer type. In addition, they analyzed risks according to age and gender. Results showed that the cancer risk of MMD patients was twice that of the general population, with the majority of the excess explained by cancers of the colon, brain, endometrium, and ovaries. The excess risk was similar in both the Swedish and Danish cohorts. The study also found that, after cancers of the genital organs were excluded, both females and males with MMD had the same excess risk of developing cancer.
A limitation of this work, according to the authors, was that they did not have information about known cancer risk factors, such as smoking. They also lacked information on which MMD type each patient had, so they were unable to determine if the increased cancer risk they observed in those with MMD was common to both or confined to a specific type.