The virus responsible for PML (progressive multifocal leukoencephalopathy), a rare brain disease that typically affects AIDS patients and other individuals with compromised immune systems, has been found to be reactivated in multiple-sclerosis patients being treated with natalizumab (Tysabri). The findings, led by scientists at Beth Israel Deaconess Medical Center (BIDMC), appear in The New England Journal of Medicine (NEJM).

“This virus - the JC virus, named for the initials of a patient - is found in about 90 percent of the population,” explains Igor Koralnik, MD, the study’s senior author and director of the Human Immunodeficiency Virus/Neurology Center at BIDMC. “But in healthy individuals the virus lies dormant in the kidneys and causes no problems.” Urine samples of healthy individuals may, therefore, show evidence of the benign virus.

But, according to Koralnik, who is also Associate Professor of Neurology at Harvard Medical School and a world leader in the study of PML, among AIDS patients and other patients with compromised immune systems, the JC virus can reactivate and travel to the brain, leading to the development of PML, a destructive brain disorder that may cause numerous neurological symptoms, including dementia, blindness, paralysis, and seizures. There is no cure for PML and more than half of all PML patients die within a year of diagnosis.

Four years ago, PML was diagnosed in two patients who were participating in a clinical trial testing natalizumab, a new drug for the treatment of multiple sclerosis (MS). An autoimmune disease caused by the migration of the immune system’s T lymphocytes to the brain, MS results in relapsing and remitting neurologic dysfunction when the T lymphocytes attack the myelin, the insulating sheath that covers the nerves.

“This was the first time we had seen PML develop in patients with multiple sclerosis,” notes Koralnik. Because natalizumab, or Tysabri, prevents lymphocytes from crossing the blood-vessel wall, some doctors theorized that it was also providing an opportunity for the dormant PML virus to take hold. “The drug appeared to be something of a double-edged sword,” notes Koralnik. “Not only was it keeping dangerous cells from entering the brain, it was also keeping out the protective virus-fighting lymphocytes, thereby leaving patients vulnerable to this dangerous infection.

“If impaired immune surveillance due to natalizumab treatment was responsible for the development of PML, we wanted to find out where in the body the JC virus reactivation was taking place,” he adds, explaining that the scientists also wanted to determine whether the reactivated JC virus had the benign molecular composition commonly found in the urine of healthy individuals - or if it had acquired changes typically found only in the brains of patients with PML.

To answer these questions, the scientists enrolled 19 multiple sclerosis patients for a clinical study as they began treatment with natalizumab. They then followed them at intervals of three, six, 12 and 18 months, post-treatment.

Their results showed that measurements of the JC virus in patients’ urine increased from 19 percent (before beginning treatment) to 63 percent after 12 months of using natalizumab. Six months later - 18 months after beginning treatment - blood samples further revealed that the virus had additionally entered the blood cells of 60 percent of these patients. (At 12 months of treatment, only one patient had the virus in their blood.)

“These JC virus measures were higher than viral measures found in patients infected with the HIV virus, and similar to measures seen in patients with full-blown PML,” explains Koralnik.

The researchers then proceeded to evaluate patients’ immune responses against the JC virus, since these immune blood cells play a crucial role in the containment of PML.

“What we saw surprised us,” he adds. “Between six and 12 months after beginning the natalizumab treatment, there was a significant drop in the magnitude of patients’ immune responses against the virus. Since natalizumab was only supposed to prevent migration of lymphocytes out of the bloodstream - but not directly alter their potency - this finding was quite unexpected.”

Finally, he adds, the scientists made another startling discovery: Further analysis showed that among many of the MS patients using natalizumab, the JC virus that was detected in their urine or blood samples had already acquired the signature changes associated with the virus’s ability to reach the brain and cause PML.

“This pilot study shows for the first time that natalizumab not only prevents the migration of protective T lymphocytes, but it also directly affects the cells’ potency against the JC virus,” says Koralnik. “It further tells us that reactivation and transformation of the virus may first occur in the kidney and that once the activated virus spills into the blood it can easily spread to the brain.”

Because none of the 19 patients tested developed any symptoms or brain lesions suggestive of PML during the course of the study, the authors do not suggest any change in the management of multiple sclerosis.

“As of July 24, 2009, there was a worldwide total of 13 natalizumab-treated MS patients who had developed PML,” he adds. “We hope that the results of our study will stimulate further research, and that monitoring the appearance of the virus in the blood and urine may allow for early identification of natalizumab-treated patients at risk of developing PML.”

This study was supported, in part, by grants from the National Institutes of Health.

Coauthors include BIDMC investigators Yiping Chen, MD, PhD (first author), Evelyn Bord, Troy Tompkins, Janice Miller, Chen Tan, MD, R. Philip Kinkel, MD, Marion Stein, MD, and Long Ngo, PhD; and Raphael Viscidi, MD, of Johns Hopkins University School of Medicine.

Source:
Bonnie Prescott

Beth Israel Deaconess Medical Center

View drug information on Tysabri.

The following summarizes selected women’s health-related blog entries.

• “National and State ACLU File Suit To End Ab-Only Funding in Mississippi,” Jodi Jacobson, RH Reality Check: The American Civil Liberties Union on Monday “asked a federal court in Mississippi to end government funding of religion in the state’s abstinence-only-until-marriage program,” Jacobson writes. According to the lawsuit, religious themes were used in the state Department of Human Services’ annual teen abstinence summit in 2008 and 2009. Kristy Bennett, staff attorney with ACLU of Mississippi, noted that studies have shown that abstinence-only sex education programs are ineffective at preventing teen pregnancy or the spread of sexually transmitted infections. Bennett also said, “‘Given the high rates of teen pregnancy and HIV infection in Mississippi, the failings of this year’s summit are inexcusable.’” According to Jacobson, Congress since 1996 has appropriated more than $1.5 billion “for programs that focus solely on promoting abstinence and censoring information that young people need to make healthy and responsible decisions about sexuality.” She concludes that “studies show that curricula that stress waiting to have sex while providing information about effective contraceptive use can significantly delay the initiation of sex, reduce the frequency of sex and the number of sexual partners and increase condom or contraceptive use among sexually active teens” (Jacobson, RH Reality Check, 9/9).
  
• “Religious Progressives Raise Concerns About Abortion in Health Care Reform,” Dan Gilgoff, U.S. News & World Report’s “God & Country”: Left-leaning religious advocates who support health care reform are pressuring Democrats to revise Rep. Lois Capps’ (D-Calif.) amendment on abortion coverage under the House health reform bill (HR 3200). One idea the advocates are floating is to create a second public health insurance plan that excludes abortion coverage, Gilgoff reports. Another suggestion is to offer abortion coverage as a supplemental insurance rider. Chris Korzen, executive director of Catholics United, said that the Capps amendment “‘addresses the vast majority of concerns [of] the moderate pro-life community’” with regard to provider “conscience” protections and abortion coverage. However, the “‘question of how to handle abortion coverage in the public option has proven more difficult to answer,’” Korzen said. According to Gilgoff, progressive religious groups are concerned “that without revising abortion provisions in the public option, the debate over abortion can bring down the whole health care reform effort.” He adds, “Progressive faith groups have been an important part of the Democratic coalition pushing for health care reform, making a moral case for the effort in the face of opposition from conservative religious activities and lending organizing muscle” (Gilgoff, “God & Country,” U.S. News & World Report, 9/9).
  
• “Reproductive Health in the Baucus Plan,” Dana Goldstein, American Prospect’s “Tapped”: Goldstein asks, “After health reform, who will decide what medical services insurance companies must cover ” The House bill (HR 3200) and Senate Health, Education, Labor and Pensions Committee’s bill would establish a committee of experts to make recommendations to the HHS secretary. Senate Finance Committee Chair Max Baucus’ (D-Mont.) plan “articulates broad areas of coverage that must be included, such as preventive care, primary care, hospital stays and maternity care,” Goldstien says. However, she writes, “Baucus would allow insurance companies themselves to define what services each of those areas include, without government interference.” Reproductive health advocates are “cautiously optimistic” about Baucus’ proposal, Goldstein reports. Adam Sonfield of the Guttmacher Institute said, “‘Services like contraception, [sexually transmitted infection] testing and treatment, and Pap tests can and certainly would fit into many of the other categories,’” such as preventive care. Abortion coverage “would likely remain unchanged” under Baucus’ plan because there is no public option, and most insurance companies already choose to cover the procedure, Goldstein writes (Goldstein, “Tapped,” American Prospect, 9/10).
  
• “Obama Isn’t Budging on Abortion in Health Care Reform” Dan Gilgoff, U.S. News & World Report’s “God & Country”: “President Obama devoted a single line of his speech” Wednesday to the growing debate about abortion coverage under health reform legislation, Gilgoff writes. The president’s assurance that federal dollars will not fund abortion “sounds like an endorsement of the House health care bill’s approach to abortion coverage,” according to Gilgoff. He adds, “It’s worth noting that Obama didn’t acknowledge the growing concern of religious progressives about Americans in the public health insurance plan being forced to fund abortions with their premiums. On abortion — and for the moment — the White House isn’t budging at all” (Gilgoff, “God & Country,” U.S. News & World Report, 9/10).
  
• “Sexism, Collusion and the Price of Eggs,” Kerry Howley, Double X’s “XX Factor”: A recent Double X article on state laws prohibiting compensation for egg donors “woke me up” and “got me thinking about the issue,” Howley writes. The “pieces spoke of blanket bans on cash for ova in scientific research,” Howley writes, adding, “By contrast, compensation for ova used by prospective mothers is generally seen as a carnivalesque open market free-for-all.” She continues that industry and reproductive groups cap such compensation “under the assumption that ova donors … should be motivated by nurturing, womanly, fuzzy fellow-feeling,” even though “no one expects a man to give up his sperm out of some heartwarming love of humanity.” Infertility clinics “are rarely challenged, and very often applauded, by left-wing consumer advocates and right-wing social conservatives trying to shield women from the true price of their ova,” Howley adds (Howley, “XX Factor,” Double X, 9/10).
  
• “Increasing Access to Abortion Through Advanced Practice Clinicians: An Advocacy Agenda,” Tracy Weitz, RH Reality Check: Weitz posts an article she recently published in the journal Contraception that examines the declining availability of abortion services and promotes a strategy to “ameliorate this problem” by increasing the number of physician assistants, nurse practitioners and certified nurse midwives. The article said it is “time to acknowledge” that such health care professionals “are capable and qualified to provide abortion care services, but the current efforts to provide this care are thwarted by both the politics of health care and the politics of abortion.” The article calls for advanced practice clinicians, reproductive health advocates, physicians and attorneys to “join together to promote the provision of abortion by APCs, thereby protecting both women’s access to abortion care and practitioners’ rights to provide essential care for their patients” (Weitz, RH Reality Check, 9/10).
  
• “Throwing Women Overboard — Again,” Martha Burk, Huffington Post blogs: In a “short — but not too sweet — message to the president,” Burk chides President Obama for appeasing Republicans by stating in Wednesday’s speech that no public funds would be used to cover abortion under his health reform plan. Burk reminds Obama, “Women put you in office, and stuck with you when the crazies were beating you up with ‘death panel’ and ’socialized medicine.’” She continues, “We still support you but like millions of women who were watching, we wonder why you have to always use our most intimate health issues as a bargaining chip to give away, when you’re not going to get anything back.” According to Burk, “You let us down once again by not calling for repeal of the restrictions on our reproductive health care that are already in place in House Appropriations Committee Chair David Obey (D-Wis.). “[W]e must work hard right now to preserve President Obama’s (and now Dave Obey’s) evidence-based pregnancy prevention funding through the full Senate vote and continue the alliance with … Obey to maintain the initiative through the conference committee reconciliation,” Newman writes. Newman then lists five lessons for advocates to learn about Obey and concludes, “We must work with Dave Obey now because when it comes to sex education, our opponents will stop at nothing” (Newman, Huffington Post blogs, 9/10).

Reprinted with kind permission from http://www.nationalpartnership.org. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.

© 2009 The Advisory Board Company. All rights reserved.

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The U.N.’s World Food Programme (WFP) made an international appeal Thursday for $5.2 million to help feed more than half a million people in Malawi through the end of next year, Agence France-Presse reports. Anne Callanan, the WFP’s country director, said although the country’s maize yield of 3.3 million tons means that there is a surplus, it “does not automatically and directly trickle down to vulnerable groups such the chronically-ill and orphans.” As a result, WFP is requesting donations to provide food for “targeted beneficiaries,” she said. “The vulnerable beneficiaries — numbering some 535,000 — include AIDS sufferers, patients receiving treatment for tuberculosis and malnourished children,” AFP writes.

This year, Malawi “produced a record maize harvest, credited to heavy investment in subsidised fertiliser and other farm inputs. However food security is still a pressing issue to poverty-stricken Malawians, who account for around 45 percent of the 13 million citizens,” the news service reports (9/10).

This information was reprinted from globalhealth.kff.org with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Global Health Policy Report, search the archives and sign up for email delivery at globalhealth.kff.org.

© Henry J. Kaiser Family Foundation. All rights reserved.