September 16, 2019

Stem Cell Study May Show Advance

The report, published online in the medical journal The Lancet, is the first to describe the effect on patients of a therapy involving human embryonic stem cells.

The paper comes two months after Geron Corporation, a stem cell industry pioneer, cast a pall over the field by abruptly halting the world’s first clinical trial based on embryonic stem cells — one aimed at treating spinal cord injury. Geron, which has not published results from the aborted trial, also said it would abandon the entire stem cell field.

The results reported Monday could help lift some of that pall. They come from the second clinical trial involving the stem cells, using a therapy developed by the company Advanced Cell Technology to treat macular degeneration, a leading cause of blindness.

“It’s a big step forward for regenerative medicine,” said Dr. Steven D. Schwartz, a retina specialist at the University of California, Los Angeles, who treated the two patients.

Both patients, who were legally blind, told researchers that they had gains in eyesight that were meaningful for them. One said she could see colors better and was able to thread a needle and sew on a button for the first time in years. The other said she was able to navigate a shopping mall by herself.

Still, it is hard to judge much from only two patients, especially when there was no control group given a placebo treatment.

Indeed, Dr. Schwartz said that the improvement in vision of the woman who could go to the mall might have been a placebo effect, though he thought the improvement in the other patient did result from the implanted cells.

Yet another reason to be cautious is that Advanced Cell Technology has had a reputation for publicizing its positive work, in part because it has often been on the brink of insolvency.

The company’s stock was up 6 percent to 15 cents a share Monday.

Advanced Cell’s desire for publicity — its scientists are co-authors of the paper — could be one reason that the paper was published after only two patients out of a planned 24 were treated.

“It’s extremely unusual and it is contrary to my usual behavior,” Dr. Schwartz said of the early publication. But he said there was huge interest in the results. “I think it’s important for the field to have something positive,” he said.

Human embryonic stem cells can theoretically be turned into any type of cell in the body. Researchers envision one day making replacement cells and tissues for damaged organs, treating a wide range of diseases.

But the field has been controversial because the creation of the stem cells usually entails the destruction of human embryos.

In this case, researchers at Advanced Cell Technology turned embryonic stem cells into retinal pigment epithelial cells. Those cells help support the light detectors in the eye. Deterioration of these retinal cells can lead to damage to the macula, the central part of the retina, and to loss of the straight-ahead vision necessary to recognize faces, watch television or read.

Some 50,000 of the cells were implanted last July under the retinas in one eye of each woman in surgeries that took about 30 minutes.

One woman, Sue Freeman, who is in her 70s, suffered from the dry form of age-related macular degeneration, one of the leading causes of severe vision loss in the elderly.

The other, who asked that her name not be used to protect her privacy, was a 51-year-old graphic designer in Los Angeles with Stargardt’s macular dystrophy, which tends to occur in younger people.

There are no approved drugs for either disease.

One safety concern in using embryonic stem cells is that if any of the cells get into the body, they could form tumors. The researchers reported that this did not happen in the first four months after the surgery and that there were no obvious safety problems.

The women were given low doses of drugs to suppress the body’s immune system and prevent them from rejecting the implanted cells, even though the eye is somewhat shielded from the immune system.

Before the treatment, the woman with Stargardt’s was able to see the motion of a hand being waved in front of her but could not read any letters on an eye chart.

Twelve weeks after the treatment, she was able to read five of the biggest letters on the eye chart with the treated eye, corresponding to 20/800 vision, according to the paper.

“I kind of did have a day when I woke up and said there really is a difference here,” the woman said in an interview in late October, about three months after the surgery. “I want my other eye done.”

Ms. Freeman, who lives in Laguna Beach, Calif., went from being able to read 21 letters on an eye chart before treatment to 28 letters six weeks after treatment, an improvement to 20/320 from 20/500 vision, according to the paper.

However, vision in her untreated eye also improved somewhat, and Dr. Schwartz said that after a while he could not detect any evidence in her eye of the implanted cells, possibly because she stopped taking the drug to suppress her immune system, owing to side effects.

That is why, he said, he thought the effect might have been a placebo effect.

The trial is now continuing and expanding beyond U.C.L.A., and using gradually higher doses of cells. A patient with Stargardt’s was implanted in London on Friday.

Article source: http://feeds.nytimes.com/click.phdo?i=91d8d90d3b8f0c92e276752163a62463

New Models of Hip and Knee Implants Not Better, Study Finds

The study, which draws on data from Australia’s orthopedic registry, covered implants introduced from 2003 to 2007 and was published this week. The findings are significant for patients in the United States because many of the new designs, like so-called metal-on-metal hips, are widely used here. Those implants, which have both a ball and cup made of metal, are expected to fail prematurely in tens of thousands of patients rather than lasting 15 years or more as artificial joints are supposed to do.

The Australian study showed that not a single new artificial hip or knee introduced over a recent five-year period was any more durable than older ones. In fact, 30 percent of them fared worse.

The Australian study concluded that both patients and taxpayer-financed health care programs were paying a high cost because surgeons were using newly designed implants, introduced with little test data, over existing designs that had track records.

“Not only has the introduction of this technology been potentially detrimental to patient care, but the current approach may be an important driver of increased health care costs,” the review concluded.

Dr. Stephen E. Graves, the director of the Australian registry and a co-author of the study, said he believed that surgeons, hospitals and regulators should closely look at the review’s results. In the case of the all-metal hips, some experts say they believe that replacing them may cost companies, insurers and taxpayers billions of dollars.

“There needs to be a careful re-evaluation of current deficiencies in regulation,” Dr. Graves said in a recent e-mail.

The Australian review is part of a special issue of a medical journal, The Journal of Bone and Joint Surgery, devoted to studies that examine the benefits and the limitations of orthopedic registries. While America does not have a registry, the Food and Drug Administration is financing efforts to see whether data from sources like overseas databases and registries run by hospitals here can be used to better monitor device performance.

Many experts argue that such efforts are essential because 700,000 Americans undergo hip or knee replacement every year, and that number is expected to increase sharply as the population ages.

In a registry, information about a patient is entered into a database when he or she receives an implant. Then, when that patient undergoes surgery again to replace that device, more data is added. By looking at large numbers of patients followed in a registry, researchers can tell whether certain device models are failing prematurely at significantly higher rates.

But researchers in England, which has a registry, pointed out in another article in the same medical journal that a product-related disaster had likely already occurred before it was detected in a such a database. As a result, some experts say they believe that there must be greater scrutiny of implants either before or after they go on the market to detect problems earlier.

Another review in the same issue found that the results of published studies that accompany the introduction of new implants could bear little resemblance to registry findings about a device’s success once it went into broader use.

That problem occurs, the review by Australian researchers found, because surgeons involved in the original published reports are often involved in its development and may have a financial stake in them. In addition, such reviews tend to be short term.

Some surgeons say they believe that one type of all-metal implant known as a resurfacing device is permitting some patients to remain more active. However, data indicates that such benefits are limited to one group of patients, namely larger, middle-aged men.

This month, bipartisan legislation was introduced in the Senate that could force manufacturers to track the performance of implants like artificial hips after they have been approved for sale. Proponents of the bill acknowledge that the measure faces an uphill fight.

Both device producers and their allies in Congress have maintained that any additional F.D.A. regulations would slow the development and marketing of innovative products that benefit patients. For his part, Dr. Graves, the Australian official, said he believed that such arguments were misleading.

“The purpose of regulation is not to impede innovation but to ensure safety and effectiveness of medical devices,” he stated. “This protects patients, but it also protects companies.”

Article source: http://feeds.nytimes.com/click.phdo?i=2ec292aa0b22873b3c2cd93f3be388af

Medtronic Giving Yale Grant to Review Bone Growth Data

Facing intensifying scrutiny over one of its bone growth products, Medtronic announced Wednesday that it was giving a $2.5 million grant to Yale to oversee a complete review of the study data that examined the product’s safety and effectiveness.

In June, a medical journal charged that researchers sponsored by Medtronic had generated misleading studies about the product, called Infuse, that overstated its benefits and asserted that it did not pose risks.

Infuse is a bioengineered material used primarily in spinal fusions, a procedure in which vertebrae are joined to reduce back pain. Industry analysts have speculated that sales of Infuse have dropped since the periodical, The Spine Journal, published its special issue on the product.

Experts said that Medtronic’s action was the first time that a medical device maker would turn over the underlying and detailed patient data from company-sponsored studies to independent experts so that they could review it and draw their own conclusions.

Typically, companies release only summaries of that information, a practice that can hamstring the ability of experts to examine it.

Infuse has been used in about a quarter of the estimated 432,000 spinal fusions performed in the United States each year.

When The Spine Journal special issue first appeared, the company announced that it would respond to the publication’s assertions by conducting a review of all Infuse-related study information.

Under the plan announced Friday, Yale will use the $2.5 million provided by Medtronic to assemble of panel of outside experts, who will then commission two academically recognized research organizations to review the company’s study data.

Dr. Harlan Krumholz, a cardiologist at Yale, who will oversee the effort, said that Medtronic’s decision was groundbreaking because it would allow independent researchers to assess the underlying data supporting a product’s safety and effectiveness.

“Published data is often missing critical information,” Dr. Krumholz said.

Dr. Eugene Carragee, editor of The Spine Journal, said he was pleased that Medtronic officials had decided to release the data.

The plan will give access to the study data to other researchers along with the groups Yale retains.

Dr. Carragee, a professor at Stanford, said that he remained concerned that little study data exists for one major use of Infuse, a type of spinal fusion, because a study of that application was halted early when patients suffered complications.

Still, he added Medtronic’s decision was “a big step in the right direction”.

Side effects associated with Infuse include infection, bone loss, unwanted bone growth and male sterility.

A stronger version of Infuse called Amplify, was recently rejected for approval by the Food and Drug because of concerns about possible cancer risks.

Along with the recent issue of The Spine Journal, the Justice Department is conducting a criminal investigation of Medtronic’s marketing of the product and a Senate committee is also conducting an inquiry.

Medtronic has not been accused of any wrongdoing, and researchers who conducted research on Infuse have defended their findings.

Article source: http://feeds.nytimes.com/click.phdo?i=f7b810f5e9af8de32eaa623e943d352e