Daily Diagnosis: Panel Says Gene Therapy Trial May Not Have Led To Participant's Death

[김나래]

A Sampling of Today’s Health & Medical News

Tuesday, September 18, 2007

• LEADING THE NEWS • PATHOLOGY AND LABORATORY MEDICINE • MEDICAL RESEARCH • GENERAL HEALTH NEWS • INFECTIOUS DISEASE • MEDICAL/LEGAL ISSUES • PATIENT SAFETY • HEALTHCARE POLICY • PUBLIC HEALTH •

Leading the News

NIH panel says gene therapy trial may not have led to participant's death.
In continuing coverage from previous briefings, the Washington Post (9/18, A4, Weiss) reports that autopsy results from Jolee Mohr, the "Illinois woman who died mysteriously in July after getting an experimental gene treatment, show no evidence that she was killed directly by the genetically altered viruses she was given, a committee of experts was told yesterday." The National Institutes of Health (NIH) Recombinant DNA Advisory Committee has been investigating the case, and concluded that "further tests will have to be done to see if the treatment somehow contributed to her death, perhaps by leaving her vulnerable to a runaway fungal infection." Meanwhile, the FDA has halted the experiment, "and the case is being watched closely by leaders of other gene therapy experiments, dozens of which are using similar viruses." According to the autopsy performed on Mohr, her death was largely the result of "a massive infection caused by Histoplasma capsulatum, a fungus common in the Mississippi and Ohio River valleys."
      The AP (9/18, Bridges) adds that the autopsy also found a "nearly eight-pound pool of blood in her abdomen [that] had crowded out her kidneys and was pressing on her lungs." Though the cause of this bleeding is undetermined, doctors speculate that it "likely hastened her death." And, "The autopsy also found signs of fungal infection in her liver, lungs, bone marrow and elsewhere." These autopsy results confirmed what the drug trial company, Targeted Genetics, had previously stated -- that "Mohr might have died of the fungal infection." As a result of the findings, "[p]anelists questioned whether Mohr should have received that shot, since she appeared already to have been complaining of sickness, including fatigue."
      According to the Seattle Times (9/18, Gonzalez), the NIH panel's chair, Howard Federoff, said that the group will "'reserve judgment' until all data is gathered, possibly by the group's next meeting in December." And, "Despite nearly eight weeks of study since the Illinois woman died July 24, scientists are still not in agreement on the immediate cause of death." The Times continues, "Mohr's death underscores the question of whether gene therapy, a biotechnology frontier in which no therapy has yet been approved, should be tried in patients with nonterminal conditions."
      The New York Times (9/18, A22, Pollack) notes, "Ms. Mohr was also taking regular injections of Humira (adalimumab), a drug similar to Enbrel (etanercept) that has also been linked to infections, including histoplasmosis." In addition, she was taking "two other immune-suppressing drugs." However, the Times continues, "If Ms. Mohr's death is eventually tied to the gene therapy, it could set back a field that has already had its share of failures and black eyes, including the death in 1999 of a teenager, Jesse Gelsinger, in a gene therapy test at the University of Pennsylvania." Currently, the virus injected into Mohr's knee, which "has widely been considered safe,...is being used in 35 other trials." Although "some panel members said the role of the gene therapy in Ms. Mohr's death might never be definitively determined," others questioned the ethics of the study, and "said [that] Ms. Mohr might not have been given enough time to consider whether to enroll in the trial," and may have been under the belief that "she would benefit from the trial, even though its main purpose was to gather information" because she was enrolled in it by her rheumatologist.
      In Wired's Wired Science blog, Brandon Keim (9/17) examined this ethical dillema, and asked, "While running a trial to determine whether a treatment is safe, how do you explain that treatment's hypothetical mechanism without giving patients the impression that it might work?" He added that according to bioethicist Robyn Shapiro, who spoke at the panel's meeting, studies must be presented "in a way that doesn't imply that the logic driving the hypothesis is fact." However, Keim added that "in Jolee Mohr's trial, there was an even bigger problem. The timing of injections was based on clinical symptoms," with the second of two shots being administered "within a flexible period of time, depending on the state of the arthritic joint. That, naturally, made the study look like it was supposed to treat the disease, when that was not actually its purpose."
      NPR (9/17) also covered this story.

From the ASCP

Deadline Extended For ASCP Fellow Award Nominations
Do you know someone who deserves to be honored with an ASCP Award? The ASCP presents four different and unique awards to pathologists each fall during the ASCP Annual Meeting. The deadline date to send nominations for 2008 awards has been extended to September 30, 2007. Nominate someone today!

Pathology and Laboratory Medicine

Scientist develops new test to detect chemical-related DNA damage.
In its Health Highlights section, HealthDay (9/18) reports, "An American scientist has developed a new DNA test that may help determine if a person's health has been harmed by exposure to chemicals," according to the BBC News. The new test uses a technique "called msds1, [and] can read specific patterns of DNA changes triggered by exposure to chemicals." DNA samples are extracted from healthy people "and exposed to specific chemicals to see which genes are affected." These results can then be "compared to a claimant's DNA, BBC News reported." Results from these test have "been used in more than 20 civil court cases in California, including one involving a man who was exposed to more than eight chemicals and developed gall bladder cancer."

Cold therapy may be used to treat cardiac arrhythmia, cardiologist suggests.
The UPI (9/18) reports, "Cryoablation, a new form of catheter-delivered therapy for cardiac arrhythmias, uses extreme cold to treat irregular heart beats," according to cardiologist Dr. Walter F. Kerwin, of Cedars-Sinai Medical Center in Los Angeles. The treatment "involves a long thin tube that is inserted through a blood vessel in the groin, wrist or arm and threaded to the heart using intense cold to destroy very small, carefully selected areas of heart tissue that are causing the irregular rhythm." Kerwin notes that the technique "is especially suited for treating certain patients with high-risk arrhythmias" in cases where medications do not work or have poorly-tolerated side effects.

Surgeons conduct successful removal of gallbladder through vagina.
HealthDay (9/18, Reinberg) reports, "French surgeons report removing a gallbladder through a woman's vagina, joining a handful of surgeons around the world who are trying the novel technique." So far, two similar operations have occurred at Columbia University and the University of California, San Diego, and the procedure was also used to successfully remove an appendix. The latest surgery, reported in the September issue of the Archives of Surgery, involved a team at University Louis Pasteur in Strasbourg, who "made a small incision in the back of the vagina," and then used "specially designed instruments inserted through [that] opening" to remove the gallbladder of a 30-year-old patient.
      MedPage Today (9/18, Bankhead) adds, "The procedure required three hours to perform, and no bleeding or bile leakage occurred during the procedure." Additionally, "The patient had no postoperative pain or scars and could have left the hospital the evening of the surgery, but the team elected to keep her hospitalized overnight for observation." When examined 10 days later, "the patient had resumed all normal activities," and "reported no discharge or bleeding and no discomfort at the perineal access site."

Medical Research

HIV drugs may also treat cancer, study suggests.
The New York Times (9/18, F9, Bakalar) reports, "A drug widely used to treat HIV infection may also be effective in fighting cancer," according to a study in the journal Clinical Cancer Research. Researchers conducted "laboratory and animal tests of six protease inhibitors," and found that three of them slowed "growth in a variety of cancer cell types, in dosages that have been tolerated in patients with HIV." Of the three, Viracept (nelfinavir) showed the most promise on "60 cell lines that had been derived from nine types of tumors," including breast cancers "that are resistant to currently used cancer drugs." Due to the results, "researchers are using nelfinavir in a Phase 1 trial" that will recruit "45 people who have tumors" and "have not responded to treatment" in an effort to determine "how large a dose [of nelfinavir] can be safely administered" in cancer patients.
      Study suggests HIV patients may be able to accept some organ transplants.   The UPI (9/18) reports that "a U.S. review said new approaches have led to good outcomes for HIV-positive patients" who undergo organ transplants. According to the study, published in the journal Transplantation, "blanket exclusion of HIV-infected patients can no longer be justified based on the early results demonstrating the safety and efficacy of transplantation in this group of patients." Researchers added that studies "show promising results for kidney and liver transplants," with "one study of liver transplantation in HIV-positive patients" indicating a "three-year survival rate...[of] 73 percent -- similar to that of HIV-negative patients."

Scientists announce discovery of gene responsible for blood formation.
The UPI (9/18) reports, "U.S. cancer geneticists have discovered [that] all blood cell production in human adults depends on a gene that, if lost, results in early bone marrow failure," according to findings in the journal Cell Stem Cell. Researchers built "a mouse model to track the function of" a gene known as Mixed Lineage Leukemia, which "acts in bone marrow stem cells and controls key aspects of their growth to generate all the mature blood cells. If disrupted, it cannot work properly," potentially resulting in leukemia. Resarchers added that the discovery could pave the way for new techniques to target the gene.

Potential method to identify stem cells discovered, researchers indicate.
The UPI (9/18) reports, "Australian scientists have found a way of identifying probable stem cells in the lining of women's wombs," according to a report in the journal Human Reproduction. Researchers identified two markers, CD146 and PDGF-RB, which they were able to use to isolate mesenchymal stem-like cells (MSC) from endometrial tissue using a high speed cell sorting machine." They found that these MSC cells "were able to produce clones to form colonies of new cells at a rate that was 15 times greater than produced by the other endometrial cells." And, the researchers added that "they found [that] MSC were able to differentiate into fat, bone, cartilage and smooth muscle cells in the culture dish."

Scientists investigate gene regulation of diseases.
The UPI (9/18) reports, "British scientists said complex diseases are more likely due to genetic variation in areas controlling gene activity [rather] than in areas specifying protein code," according to a study in the current issue of the journal Nature Genetics. A team examined "nearly 14,000 genes in 270 DNA samples, looking at 2.2 million DNA sequence variants to determine which affected gene activity." They discovered that the "activity of more than 1,300 genes was affected by DNA sequence changes in regions predicted to be involved in regulating gene activity, which often lie close to, but outside, the protein-coding regions."

General Health News

Reclast may help prevent repeat hip fractures, study suggests.
The Wall Street Journal (9/18, D6, Armstrong) reports, "A variation of a drug commonly given to cancer patients with bone damage appears to be an effective tool for preventing repeat hip fractures in elderly patients," according to a study published in the New England Journal of Medicine. Researchers followed "2,127 patients" with an average age of 74 "for nearly two years." They found that "[t]he rate of new fractures" in patients injected once per year with the drug Reclast (zoledronic acid) "was 8.6 percent, compared with 13.9 percent in the placebo group." Furthermore, "The risk of death was reduced by 28 percent in the Reclast group."
      The AP (9/18) adds, "Some experts called the drop in deaths 'striking' but said other drugs could have a similar effect." However, "No other osteoporosis drug study published in at least 15 years has shown such a pronounced reduction in deaths," according to lead study author Dr. Kenneth Lyles of Duke University Medical Center.
      USA Today (9/18, Rubin) notes, "An estimated 10 million Americans have osteoporosis...and each year more than 300,000 of them suffer a hip fracture, according to the National Osteoporosis Foundation." And, "Older adults who break a hip are more likely to die in the following year and 2.5 times more likely to suffer another osteoporosis-related fracture than people the same age," according to this study's authors.
      And, the Los Angeles Times (9/18, Maugh II) points out that "[s]ome critics have charged that the study's design bordered on the unethical because patients in the control group were given placebos." However, "Lyles and the writers of the editorial said that in general, few patients receive treatment to avert future fractures. In this study, they noted, fewer than 12 percent of patients received any other therapy from their physicians, possibly because the doctors are unaware of the benefits."

Infectious Disease

Research indicates first new TB drug in 30 years may cut recovery time by two months.
Bloomberg (9/18, Lauerman) reports, "Bayer AG's Avelox (moxifloxacin hcl), set to become the first new type of medicine for tuberculosis in 30 years, may shorten treatment time by two months and slow the development of deadly, drug-resistant strains," according to "research funded by the Gates Foundation and the U.S. government." This could potentially shorten treatment of the disease from six months to four. Bloomberg adds that this week, physicians "at an infectious disease meeting...in Chicago will hear results of a clinical trial," which "will be crucial to the drug's approval as early as 2011." Currently, Avelox is "used to treat pneumonia." If approved, "Bayer [has] agreed to make the drug available in poorer nations at 'affordable' prices." Currently, treating tuberculosis "costs about $8,162" per U.S. patient, according to CDC estimates. Shortening treatment to only four months, as Avelox may potentially do, "might cut the cost to $6,536."
      Chicago hosts American Society for Microbiology conference.   The AFP (9/17, Santini) reported, "Thousands of physicians and scientists began meeting" in Chicago "Monday to debate ways to fight bacteria resistant to drugs and the effects of global-warming on germs." Billed "as the world's biggest conference on disease-causing microbes," the American Society for Microbiology "is expected to draw some 12,000 physicians, researchers and healthcare professionals" who "will address the problem of drug-resistant microbes such as tuberculosis." The group "will also discuss the risks of a possible epidemic of a form of bird flu," the "results of clinical trials on the effectiveness of anti-retroviral therapies on cancers in people with HIV" and "the antibiotic effects of statin drugs, which reduce cholesterol."

Medical/Legal Issues

New York City, state file joint lawsuit against Merck for misrepresenting the dangers of Vioxx.
The New York Sun (9/18, Solomont) reports that New York Attorney General Cuomo (D) and Mayor Michael Bloomberg (I) filed a joint lawsuit yesterday in the state Supreme Court against Merck & Co. Inc., the maker of the painkiller Vioxx (rofecoxib), for "allegedly withholding information about cardiovascular risks associated with the drug." The civil suit accuses Merck "of deliberately misrepresenting Vioxx, which Merck removed from the market in 2004 after a study showed the drug doubled the risk of heart attack or stroke." The Sun notes, "In addition to civil penalties, the lawsuit seeks Medicaid restitution stemming from $100 million the state spent on Vioxx prescriptions between 1999 and 2004. The lawsuit is the first case to be filed under the state's False Claims Act (pdf)."
      The New York Times (9/18, B3, Kershaw), the Wall Street Journal (9/18, D7, Tesoriero), and the AP (9/18) also cover the story.

Patient Safety

Children's vaccine may be causing "superbugs," study suggests.
The AP (9/18, Marchione) reports, "A vaccine that has dramatically curbed pneumonia and other serious illnesses in children is also having an unfortunate effect: promoting new superbugs that cause ear infections," according to Dr. Michael Pichichero, a University of Rochester Medical Center microbiologist. Physicians reportedly have identified the first germ "that is resistant to all drugs approved to treat childhood ear infections." Thus far, "[n]ine toddlers in Rochester, N.Y., have had the bug and researchers say it may be turning up elsewhere, too." The AP continues, "Prevnar (Diphtheria CRM Protein) prevents seven strains responsible for most cases of pneumonia, meningitis and deadly bloodstream infections." However, "dozens more strep strains exist, and some have flourished and become impervious to antibiotics since the vaccine combats the more common strains." Drugmaker Wyeth "anticipated this and is testing a second-generation vaccine." However, that vaccine "is at least two years from reaching the market, and the new strains could become a public health problem in the meantime if they spread hard-to-treat infections through day care centers and schools."

Healthcare Policy

Agency report finds states differ widely in spending on healthcare.
The New York Times (9/18, A22, Pear) reports that according to a study appearing in the Web edition of the journal Health Affairs, a huge variation exists "in personal health spending among states, ranging from an average of nearly $6,700 a person in Massachusetts to less than $4,000 in Utah." The study "said that Massachusetts, Maine, New York, Alaska and Connecticut had the highest per capita spending on healthcare in 2004," while the "lowest-spending states were Utah, Arizona, Idaho, New Mexico and Nevada.  Per capita spending in Utah was 59 percent of that in Massachusetts." The lead author of the report, Anne B. Martin, an economist at the Centers for Medicare and Medicaid Services, "said [that] the reasons for the differences included the age and incomes of the population, the concentration of doctors in a state, the generosity of public programs, the extent of private health insurance coverage and the mix of services used by state residents."

Public Health

Study suggests one-third of men do not wash hands after using the restroom.
New York Daily News (9/18) reports, "More American adults are leaving public restrooms without washing their hands, and the worst offenders are men," according to a survey released by the American Society of Microbiology during a news conference. Investigators "who staked out public potties found that one-third of men didn't bother to wash after using the bathroom, compared with 12 percent of women." When this survey was conducted two years ago, "only one-quarter of men didn't wash, compared with 10 percent of women."
      According to Brian Sansoni, spokesman for the Soap and Detergent Association, "Guys need to step up to the sink," adds the AP (9/18, Marchione). The results of this survey were based on "observations last month of more than 6,000 people in four big cities." Furthermore, "a recent Harris Interactive survey found 92 percent of Americans said they always wash up after using the bathroom." People may be getting more lax about hand-washing, as this latest survey "found that only 77 percent actually do, when it comes to public restrooms," a "6 percent decline" from 2005.
      MedPage Today (9/18, Smith) notes, "The cleanest city in the survey was Chicago,...with 81 percent of people washing up, followed by New York at 79 percent, Atlanta at 75 percent, and San Francisco at 73 percent. And, "The worst place for men was also the best for women -- at Atlanta's Turner field, just 57 percent of men washed up, compared with 95 percent of women."
      Changes in food production may increase animal-to-human disease transmission, agency warns.   The UN News Centre (9/17) reported, "Global animal food production is undergoing a major transformation that could lead to a higher risk of disease transmission from animals to humans, and excessive concentration of animals in intensive production systems should be avoided," according to the United Nations Food and Agriculture Organization (FAO). In its policy brief entitled "Industrial Livestock Production and Global Health Risks," the FAO said that swine and "poultry production relies on a significant movement of live animals," and this "movement and the concentration of thousands of confined animals increase the likelihood of transfer of pathogens."
      The AFP (9/18) and the AP (9/18) also cover this story.