Scientists Find Clue to Dangerous Side Effect of MS Drug

Scientists may have discovered part of the reason why Tysabri, a drug used to treat multiple sclerosis, may lead to the development of a rare but potentially deadly brain disease in some patients. The drug seems to rouse the typically dormant JC virus from its slumber, allowing it to cross into the brain. Although this finding may lead to a way of predicting who is at risk for the brain infection -- called progressive multifocal leukoencephalopathy (PML) -- at this point, the implications are still unclear. "We don't know what this means until we find out over time whether or not people actually do get PML," said Patricia O'Looney, vice president of biomedical research at the National Multiple Sclerosis Society in New York City. "But it certainly is exploring a key question." The study authors also warned against coming to premature conclusions. "We don't advocate a change in management [of the disease] at this point because the clinical relevance of these findings is still unknown," said Dr. Igor J. Koralnik, senior author of a paper appearing in the Sept. 10 issue of the New England Journal of Medicine. "But it should spur further research." Natalizumab (Tysabri) first received U.S. Food and Drug Administration approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed the rare but deadly viral infection. According to the study authors, as of July 24, 2009, 13 patients with multiple sclerosis taking Tysabri are known to have developed PML, along with one patient with Crohn's disease (Tysabri was approved to treat Crohn's in early 2008). The JC virus is present yet dormant in about 90 percent of people. It can reactivate in people with AIDS or otherwise compromised immune systems. "We don't have a very good handle right now on how to determine who's at higher risk for PML," O'Looney stated. "There's no way to monitor patients and no way to predict who will be susceptible. It's important to find some marker or indication of the presence of these viruses either in the urine or the blood." In this latest study, 19 patients with relapsing-remitting multiple sclerosis who were taking Tysabri underwent lab work at three, six, 12 and 18 months after starting treatment. After 12 months, measurements of JC virus in the urine rose from 19 percent (about normal) of samples to 63 percent at 12 months. At this time, only one patient showed JC virus in their blood. By 18 months, the virus had infiltrated plasma samples in 20 percent of patients and blood cells in 60 percent of patients. And the virus type in question here had undergone a rearrangement that made it more adept at crossing into the brain. "The changes are usually only found in the brains of patients with PML [and] we think the virus acquired the [changes] during Tysabri treatment," Koranik said. Immune system responses associated with higher levels of JC virus dropped after six and 12 months of treatment. "This was unexpected," said Koralnik, who is director of the HIV/Neurology Center at Beth Israel Deaconess Medical Center in Boston. "It dampened the immune response as measured in blood samples and that was associated with the appearance of the virus in the urine." None of the patients developed PML or any indication that they might develop the infection. "The next question is: does that mean that all those who have virus in the blood or rearrangement in the urine will develop PML?" Koralnik said. "This is something that obviously we can't answer with this pilot study. The epidemiology indicates that the development of PML is still a rare event in Tysabri-treated patients, but we hope that if we follow the appearance of the virus in the blood or urine and follow changes [in the actual virus], in the future we will be able to detect better those at risk of developing PML while in treatment." Two other papers in the same issue of the journal described case studies of patients with multiple sclerosis who developed PML after using Tysabri. One was a 52-year-old man who became critically ill but eventually recovered. The second was a 35-year-old man, who also recovered. The authors of this paper stressed that the risk of PML in patients being treated with Tysabri is still low, about one in 1,000 and possibly even lower. Until there is a good way to predict who is at risk for PML, experts urged doctors to be alert for early signs of this brain infection. "Patients and physicians still need to have tight vigilance for any new symptoms that can occur while a patient is on Tysabri," O'Looney said.

Take the Load Off Your Child's Back

A backpack can be a great help to school children, but it needs to fit properly to avoid a lifetime of hurt, health-care professionals say. "If too heavy or worn incorrectly, backpacks can strain muscles and joints and cause serious back pain," Paula Kramer, who chairs the occupational therapy department at the University of the Sciences in Philadelphia, warned in a news release from the university. Backpack-related injuries resulted in 7,300 emergency room visits in 2006, according to the U.S. Consumer Product Safety Commission. Kramer offered tips for buying and using backpacks: The backpack size should correlate with the child's size and age -- smaller, younger children should have smaller backpacks. Look for reflective material on the backpack to improve visibility and padded shoulder straps for added comfort. Consider buying a backpack that can be wheeled or a triangular sling-style bag, which is worn over one shoulder and across the body, which better balances the load. When loading the backpack, put heaviest items closest to the back. This helps distribute weight more evenly. When loaded, the backpack should weigh less than 10 to 15 percent of the child's body weight. Adjust shoulder straps so the backpack fits snugly against the back. The child should always use both should straps and clip the waist belt, if the backpack has one, for added support and even weight distribution.

Medicare drug benefit gets good marks

The Medicare drug benefit may have caused confusion when it was launched in 2006, but the program has since "exceeded expectations" in getting seniors coverage and trimming their medication costs, according to a new report. A study by the non-profit research organization RAND found that by 2008, nearly 90 percent of Medicare beneficiaries had drug coverage that was at least as generous as the standard benefit required of insurers participating in the program. On average, the drug benefit -- known as Medicare Part D -- cut seniors' annual out-of-pocket costs by 16 percent, while increasing the number of prescriptions by 7 percent. "In the beginning there was a lot of concern about Medicare Part D, but we found convincing evidence that it has exceeded expectations and generally has been successful," lead researcher Dr. Geoffrey F. Joyce, a senior economist at RAND in Santa Monica, California, said in a written statement. "Most seniors now have prescription drug coverage that allows them to buy drugs at a reasonable cost," he added. What's more, the study found, much of the medication savings has been concentrated among lower-income beneficiaries. "It appears that Medicare Part D has been particularly successful in lowering costs for the poor and the disabled," Joyce said, "which is an important finding since initially there was concern these groups would be particularly vulnerable under a privately administered benefit." There is, however, still room for improvement, the RAND researchers report in the American Journal of Managed Care. For one, they write, there remains a "substantial core of seniors" -- mostly low-income individuals -- who "need to be educated that enrolling in Part D is in their own interest." The researchers also point to the issue of the so-called "doughnut hole" gap in Part D coverage. This refers to a temporary break in coverage that seniors face once their drug spending hits its specified annual limit; at this point, beneficiaries must cover their own prescription costs until they spend enough to be eligible for "catastrophic" coverage. According to one study, Joyce's team notes, 3 million Part D enrollees hit that coverage gap in 2007, and 20 percent either stopped taking their medication, cut back on doses or switched to a different drug. Still, the RAND study suggests that the private insurance plans participating in Part D are offering coverage that is comparable to at least some private and public plans not involved in the Medicare program. Joyce's team compared the 10 largest plans participating in Part D with seven non-participating public and private plans often cited as offering low-cost or generous drug coverage. They found that the Part D plans and most non-participating plans were similar as far as out-of-pocket costs and the medications each plan covered. The average out-of-pocket medication costs to seniors in 9 of the 10 Part D plans ranged from about $1,000 to $1,400. This was comparable, the researchers note, to several of the private and public plans not participating in Part D, including coverage offered by the Veterans Administration. The researchers call on the government to "continue to monitor the competitiveness of the Part D market to ensure it meets the diverse needs of Medicare beneficiaries."

Researchers Make Insulin-Producing Cells From Adult Skin Cells

Using skin cells from people with type 1 diabetes, researchers were able to produce cells that made insulin in response to changing blood sugar levels, though not as efficiently as normal insulin-producing cells do. The major immediate implication from this experiment is that scientists now have a preliminary lab model of human type 1 diabetes cells, and the hope is that an animal model of the disease could be developed from this research. Down the road, this finding could lead to a way to replace the islet cells that were destroyed when the disease first developed. "This is a big deal," said Susan Solomon, CEO of the New York Stem Cell Foundation, which provided some of the funding for the study. "Tackling the basic biology of type 1 diabetes, which is a very complex disease, is a critical step. With these cells, we can see in a dish what's happening to the immune system, and if you don't understand the immune response, you get nowhere with type 1 diabetes." "This is very preliminary data, but now we could potentially look at the interaction between immune system cells and insulin-producing cells to find the root cause or trigger, which we think might vary from patient to patient," explained Meri Firpo, an assistant professor at the Stem Cell Institute at the University of Minnesota. Results of the study will be published in this week's online edition of the Proceedings of the National Academy of Sciences. Type 1 diabetes is believed to be an autoimmune disease that destroys the insulin-producing islet (beta) cells in the pancreas. Because the body no longer produces its own insulin, people with type 1 diabetes must replace that lost insulin through injections or an insulin pump. Researchers suspect that people who develop the disease have a genetic susceptibility to the disease and that an environmental factor, such as a virus, somehow triggers the disease. In the current study, researchers from the Howard Hughes Medical Institute at the Harvard Stem Cell Institute and the Naomi Berrie Diabetes Center at Columbia University, obtained skin samples from two white males who had type 1 diabetes. One was diagnosed at 3 years of age, while the other was first diagnosed when he was 21. Normal skin cells are already specialized cells. Their job is to protect the body with a covering of skin, explained Firpo. To transform these cells into embryonic-like stem cells, essentially getting them back to the beginning when they weren't already specialized, researcher Doug Melton and his colleagues used three inserted genes to reprogram the cells, creating what's known as an induced pluripotent stem cell (iPS). In this case, the cells were then turned into insulin-producing cells. Along with helping to provide a model of type 1 diabetes, this technology might also one day be used to create islet cells for transplant from a person's own skin cells. That way, there would be no need for immunosuppressive medications. However, because the current technique uses genetic manipulation to change the cell, Firpo said long-term safety issues would have to be addressed. Mouse cells that have been similarly manipulated have developed benign tumors, she said. So, using such cells for transplant is definitely not "a near-term thing," she stressed. The practical implications from this study "are primarily research-related," said Julia Greenstein, director of beta cell replacement for the Juvenile Diabetes Research Foundation (JDRF) in New York City. She said that this study helps further at least two areas of research that JDRF is focusing on: developing a self-source for islet-cell transplants and blocking the immune response. Another area of research that JDRF is actively pursuing is the possible encapsulation of islet cells before transplantation so that they could hide from the immune system. "Our hope is that understanding all of these things will come together -- that once we've figured out how to make the cell source that we'll also have figured out how to block the immune response, but there's a lot of basic science one has to do to get there," said Greenstein. The good news, she added, is that "there's an incredible amount of exciting research that has the capacity to impact the disease in the long-term going on."

Wheat Consumption May Contribute to Diabetes

An abnormal immune response to wheat proteins may contribute to type 1 diabetes, Canadian researchers say. Their study of 42 people with type 1 diabetes found that nearly half had immune system T-cells that overreacted to wheat. The researchers also identified genes associated with this abnormal immune response. "The immune system has to find the perfect balance to defend the body against foreign invaders without hurting itself or overreacting to the environment, and this can be particularly challenging in the gut, where there is an abundance of food and bacteria," study author Dr. Fraser Scott, a senior scientist at the Ottawa Hospital Research Institute and professor of medicine at the University of Ottawa, said in a hospital news release. "Our research suggests that people with certain genes may be more likely to develop an overreaction to wheat and possibly other foods in the gut, and this may tip the balance with the immune system and make the body more likely to develop other immune problems, such as type 1 diabetes," he explained. The study appears in the August issue of Diabetes. "These observations add to the accumulating evidence that the gut is an active player in the diabetes disease process," Dr. Mikael Knip of Finland wrote in an accompanying editorial.

Protein May Identify Deadlier Breast Cancer

A protein linked to more aggressive and advanced breast cancer tumors has been identified by German researchers. The investigators analyzed 229 breast tissue samples from patients with cancer and compared them with healthy breast tissue. The study found that patients whose tumors had elevated levels of GLI1 (glioma-associated oncogene homolog 1) protein tended to have a more advanced stage of cancer, had an increased number of cancerous lymph nodes and a greater chance of death. GLI1 could be a useful measurement for determining cancer prognosis, according to the study published this week in the journal BMC Cancer. "GLI1, a mediator of the so-called 'hedgehog' signaling pathway, has previously been implicated in the development of different human tumor entities," said lead study author Edgar Dahl of RWTH Aachen's University Hospital in Germany, in a news release from the journal's publisher. "We've found a positive, significant association between overexpression of GLI1 and unfavorable overall survival outcome in human breast cancer," Dahl added. Overexpression of GLI1 has also been implicated in esophageal cancer, the researchers noted. "Taken together, these results support a role of GLI1 as a new prognostic biomarker in breast cancer," Dahl said. "Future studies will determine whether GLI1 can be successfully included into multimarker panels for early cancer detection or molecular sub-typing of breast cancer. This could support personalized breast cancer medicine."

Who should not take carisoprodol?

• Do not take carisoprodol if you have acute intermittent porphyria.
• Before taking carisoprodol, tell your doctor if you have kidney or liver disease. You may need a lower dose or special monitoring during your therapy.
• It is not known whether carisoprodol will harm an unborn baby. Do not take carisoprodol without first talking to your doctor if you are pregnant.
• It is also not known whether carisoprodol passes into breast milk. Do not take carisoprodol without first talking to your doctor if you are breast-feeding a baby.
• Carisoprodol is not approved for use in children younger than 12 years of age.