A new form of gene therapy for boys with the life-threatening condition known as “bubble boy” disease appears to be both effective and safe, according to a collaborative research team Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and other institutions conducting an international clinical trial.Early data suggest that the therapy may help patients avoid the late-developing leukemia seen in a quarter of those with the disease in pioneering gene therapy trials in Europe more than a decade ago.Eight of nine boys recruited to date into the trial are alive between 12 and 38 months after treatment, with none of the infections associated with the disease, more formally known as X-linked severe combined immunodeficiency syndrome (SCID-X1), the research team reported Thursday in the New England Journal of Medicine (NEJM).Gene therapy alone generated functioning immune systems in seven of the eight. Genetic studies of the boys’ new T-cells, which are critical components of the body’s immune system, reveal that the viral vector used to deliver the gene therapy did not lead to an expansion of cells with vector insertions near known cancer-causing genes, raising cautious hopes about the vector’s long-term safety. One child died of an overwhelming infection present at the time gene therapy began. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.The investigators will continue to monitor the patients for any signs of treatment-related leukemia for 15 years. In the prior European trials — which were the first to demonstrate gene therapy’s potential to cure a disease — leukemia appeared two to five years after treatment. This outcome was one of several events that together slowed clinical progress in gene therapy for many years.The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on genes, called oncogenes, which could lead to leukemia.“Our goal was to take the molecular data from the prior trial and use it to produce a vector that would remain effective and at the same time reduce the risk of leukemia,” said David A. Williams, HMS Leland Fikes Professor of Pediatrics, chair of the hematology/oncology division at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, director of clinical and translational research at Boston Children’s Hospital, principal investigator for the gene therapy trial’s U.S. sites, and corresponding senior author of the NEJM paper.“The efficacy data from our study is clear: The vector does work to correct the disease. And by a surrogate endpoint, we have improved the treatment’s safety, although it’s too early to say that we’ve completely eliminated the long-term risk of leukemia,” he said.After a single round of treatment, six of the seven boys for whom the gene therapy was successful had achieved the trial’s primary efficacy endpoints: a T-cell count greater than 300 cells per microliter of blood and T-cell proliferation in response to stimulation with phytohemagglutinin (a test used to measure T-cells’ ability to react to pathogens).The seventh boy received a second round of gene therapy and remains healthy despite relatively low T-cell counts. The eighth surviving patient was successfully treated with a conventional hematopoietic (blood-forming) stem cell transplant after gene therapy failed to stimulate T-cell production.“Only a minority of babies with SCID-X1 have the optimal donor for standard transplant, a brother or sister who is tissue-type matched,” said co-lead author Sung-Yun Pai, assistant professor of pediatrics at HMS and a pediatric hematologist/oncologist at Dana-Farber/Boston Children’s. “For the rest, gene therapy is a therapeutic option that avoids the need to find an alternative donor and avoids complications of allogeneic transplant such as graft-versus-host-disease.”The core question of the trial was whether the new self-inactivating viral vector could safely and successfully shuttle a gene called the IL-2 receptor gamma (IL2RG) subunit into the patients’ hematopoietic stem cells. In boys born with SCID-X1, mutations render the IL2RG gene inactive, robbing the children of the ability to produce a functional immune system.In addition to Dana-Farber/Boston Children’s, Necker Children’s Hospital in Paris, Great Ormond Street Hospital in London, Cincinnati Children’s Hospital Medical Center, and UCLA Mattel Children’s Hospital UCLA are participating in the international clinical trial.“This trial represents the best in collaborative efforts from a number of the leading gene therapy centers worldwide that allowed us to accomplish its goals in a relatively short period of time,” Williams said. “The success of the trial was also critically dependent on funding from the National Institutes of Health.”Adapted from a Dana-Farber/Boston Children’s Cancer and Blood Disorders Center news release.
RelatedPosts Tyson Fury to Anthony Joshua: Don’t risk fighting Usyk Anthony Joshua, Okolie plot world title double Anthony Joshua wants Tyson Fury, Wilder fight Deontay Wilder will sack his trainer Mark Breland after being left angered that he had thrown the towel in in a knockout defeat to Tyson Fury. Wilder’s corner threw in the towel in the seventh round of the Las Vegas showpiece and it was viewed as a sensible call after the Alabama fighter had been dropped twice earlier in the fight. But Wilder, and head trainer Jay Deas, spoke after the defeat that they did not agree with the move and the heavyweight is now ready to shake-up his team as a consequence. Wilder has revealed he will activate his rematch clause option for a trilogy fight and he will go into that fight with a new trainer. Speaking to Yahoo, Wilder said: “I am upset with Mark for the simple fact that we’ve talked about this many times and it’s not emotional. “It is not an emotional thing, it’s a principle thing. We’ve talked about this situation many, many years before this even happened. “I said as a warrior, as a champion, as a leader, as a ruler, I want to go out on my shield. “If I’m talking about going in and killing a man, I respect the same way. “I abide by the same principal of receiving. “So I told my team to never, ever, no matter what it may look like, to never throw the towel in with me because I’m a special kind. “I still had five rounds left. “No matter what it looked like, I was still in the fight.” Former US fighter Andre Ward was among those defending Breland’s call to end the fight early. Ward tweeted: “I respect Mark Breland. “We need more trainers like him in the sport of boxing. “I stand with you Coach.” Wilder produced a disappointing display as he was roundly beaten by Fury and he has since blamed the referee and his own ringwalk costume for his lacklustre display. The American wore a black and red armoured body suit with a matching mask and crown, weighing a total of 40lbs, as he made his way to the squared circle for his second bout with Fury at the MGM Grand in Las Vegas on Saturday. While there had been some talk of a unification bout for Fury with Anthony Joshua, it appears the focus will now be a third installment of Wilder-Fury. “The rematch is definitely going to happen,” Wilder added to The Athletic. “We’re going to get it on. I want to get right back to it.” Fury, as the winner of the second bout, would be entitled to a 60/40 percentage split of all the money on the line for the fight, plus the earnings from PPV and ticket sales.Tags: Anthony JoshuaDeontay WilderJay DeasMark BrelandTyson Fury
Facebook Twitter Google+ Allegations that men’s basketball associate head coach Bernie Fine molested a former team ball boy have sparked surprised reactions on and around the Syracuse University campus. ‘Wow,’ said Clarice Muron-Bendaoud, an undeclared sophomore in the College of Arts and Sciences. ‘Everybody was so worked up about Penn State; nobody imagined it would happen here.’ The Syracuse police began investigating an allegation against Fine on Thursday. Fine is accused of molesting Bobby Davis, now 39, for more than 12 years starting in 1984. Athletic Director Daryl Gross put Fine on administrative leave Thursday night upon a request from Chancellor Nancy Cantor, according to a statement from Kevin Quinn, senior vice president for public affairs for the university. Zach Ehler, a freshman accounting major, said this is just one of many stories that will emerge in the wake of the Penn State sex abuse scandal. ‘A lot more stories are going to come out after Sandusky,’ Ehler said. ‘We’re just the first school it’s happening to.’AdvertisementThis is placeholder text Davis reported the abuse to Syracuse police in 2003 but was told the statute of limitations had run out, according to an article published by ESPN. SU launched its own investigation in 2005 after an unidentified male reported inappropriate conduct by an associate men’s basketball coach to the Syracuse Police Department, according to the statement from Quinn. The university will fully cooperate with the police, the statement said. Some students are skeptical of the situation, placing the responsibility on head coach Jim Boeheim. ‘I’m not surprised,’ said Andreas Nicolos, an undeclared freshman in the David B. Falk College of Sport and Human Dynamics. ‘I was telling my friend they shouldn’t have named the court after Boeheim. You never know what will happen after he’s gone.’ Nicolos mentioned that Dennis Duval, Syracuse police chief at the time of the investigation, was a former SU men’s basketball player under Boeheim. He said that fact definitely makes matters worse, and it isn’t looking good for the credibility of the defense. Upon immediately hearing the news, a group of men at Starbucks on Marshall Street carried varying opinions on the allegations surrounding Fine. Shpend Behrami, a Syracuse resident and Morrisville State College graduate, said Boeheim should not be in the limelight or receive harsh criticism. ‘These are just allegations — that’s not proof,’ Behrami said. ‘The heat shouldn’t be on Boeheim if the school knew. They should be focused on the assistant coach. And where were the kid’s parents if this was going on for so long?’ Dalmat Istogu, another at the table, agreed that Boeheim should not be blamed in this situation. ‘His job is to coach and anything that happens outside of coaching is not his responsibility,’ said Istogu, a senior accounting major. ‘Other people have jobs to investigate that.’ Whether or not the allegations are true, the simple fact that this news is breaking at SU to begin with is unfortunate, said Elizabeth Boyke, a junior musical theater major. ‘I really love our school and for that misuse of trust to exist, it’s just horrible,’ Boyke said. ‘Hopefully justice is seen for people who were doing wrong.’ Aaron Duprey, a sophomore economics major, said this development could be devastating for the program and the university as a whole. ‘But if someone knew something and didn’t do anything, then it’s a problem,’ Duprey said. Zach Settembre, a former SU basketball student manager and senior public relations major, said the allegations against Fine are simply unexpected. ‘Bernie Fine was first class with me, and I have absolutely never seen anything to suggest any of that,’ Settembre said. ‘He’s a staple of Syracuse basketball and that is totally out of left field, so he’s always been first class to me, he’s helped me a lot as a young coach.’ [email protected] —Asst. Sports Editor Mark Cooper contributed reporting to this article. Published on November 17, 2011 at 12:00 pm Comments