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Combination gene therapy treats age-related diseases

first_img Genome editing with precision Related Optimized gene-editing system halts hearing loss in mice with hereditary deafness Breakthrough research shows that stem cell genes can be edited in living systems Editing genes at the source Importantly, the injected genes remained separate from the animals’ native genomes, did not modify their DNA, and could not be passed to future generations or between living animals.“Achieving these results in nontransgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease,” said Church, who is also a professor of genetics at HMS and professor of health sciences and technology at Harvard and MIT. “This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself.”Church, Davidsohn, and co-author Daniel Oliver are co-founders of Rejuvenate Bio, a biotechnology company that is pursuing gene-therapy treatments for dogs. Each holds equity in Rejuvenate Bio.“The finding that targeting one or two key genes has therapeutic effects in multiple diseases makes enormous sense from the perspective of pathophysiology, but this is not how drugs are normally developed. This ability to tackle several age-related diseases at once using gene therapy offers a potential path to make aging a more manageable and less debilitating process,” said Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as professor of bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences.Additional authors of the paper include Wyss Institute members Andya Vernet and Amanda Graveline; former Wyss Institute members Oliver, Matthew Pezone, and Shimyn Slomovic; Sukanya Punthambaker from the Wyss Institute and HMS; and Xiaoming Sun, Joseph Bonventre, and Ronglih Liao from Brigham and Women’s Hospital.The research was supported by the National Institutes of Health and the Merkin Family Foundation.center_img The Daily Gazette Sign up for daily emails to get the latest Harvard news. As people age, they tend to develop diseases such as heart failure, kidney failure, diabetes, and obesity, and the presence of any one disease increases the risk of developing others. Traditional drug treatments, however, each target one condition. That means patients often have to take multiple medications, increasing both the risk of negative side effects and the likelihood of forgetting one.New research from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) suggests that it may be possible someday to tend to multiple ailments with one treatment.In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases, suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan. The research is reported in PNAS.“The results we saw were stunning and suggest that holistically addressing aging via gene therapy could be more effective than the piecemeal approach that currently exists,” said first author Noah Davidsohn, a former research scientist at the Wyss Institute and HMS who is now chief technology officer of Rejuvenate Bio. “Everyone wants to stay as healthy as possible for as long as possible, and this study is a first step toward reducing the suffering caused by debilitating diseases.”The study was conducted in the lab of Wyss core faculty member George Church as part of Davidsohn’s postdoctoral research into the genetics of aging. Davidsohn, Church, and their co-authors homed in on three genes that had been shown to confer increased health and lifespan benefits in mice that were genetically engineered to overexpress them: FGF21, sTGFβR2, and αKlotho. They hypothesized that providing extra copies of those genes to nonengineered mice via gene therapy would similarly combat age-related diseases and bring health benefits.The team created separate gene therapy constructs for each gene using the AAV8 serotype as a delivery vehicle, and injected them into mouse models of obesity, Type 2 diabetes, heart failure, and renal failure both individually and in combination with the other genes to see whether there was a positive synergistic effect.FGF21 caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFβR2 reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFβR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFβR2 could successfully treat all four age-related conditions, therefore improving health and survival. Administering all three genes together resulted in slightly worse outcomes, likely from an adverse interaction between FGF21 and αKlotho, which remains to be studied. Prime editing system offers wide range of versatility in human cells, correcting disease-causing genetic variations Single letter speaks volumeslast_img read more

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4,000 COVID-19 tests on hand in Broome County

first_imgGarnar says the county requested 6,000 tests and is looking to find more. He says he’d “sell his soul” to get more tests. 12 News will have more coverage of this story in its 5, 5:30 and 6 p.m. newscasts. (WBNG) — Broome County Executive Jason Garnar announced the county now has 4,000 COVID-19 tests available. The county executive says there should be a large expansion of testing coming. A map detailing where cases are located in the county can be found by clicking here. Broome County April 6 coronavirus update There are 72 positive cases of the virus in the county. 13 people have been hospitalized and 45 are at home. Nine people have recovered. According to county officials, 3,000 tests cost about $16,000. 18 people are in precautionary quarantine and 133 are in mandatory quarantine. Coronavirus numbers Garnar says a fifth person in Broome County has passed away from the coronavirus. The victim was a male in their 80s. 21 cases are pending. Testinglast_img read more

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Commission launches infringement action against 17 states over IORP II

first_imgThe European Commission has opened infringement cases against 17 EU countries in relation to the transposition of IORP II, the new EU pension fund directive.The infringement proceedings relate to “non-communication cases”, meaning a member state has failed to communicate measures that fully incorporate into national law the provisions of an EU directive by the transposition deadline.IPE understands that it is fairly routine for the Commission to initiate such proceedings.According to its website, so far this year the Commission has made decisions relating to 217 active infringement cases for “non-communication” of transposition measures across all policy areas. A policy official at one national pension fund association told IPE she was more surprised by the speed at which the Commission had acted in the case of the IORP II directive.In January the Commission had said it would “carefully examine” how each member state had implemented the directive. The deadline for incorporating IORP II into national law was 13 January.The infringement proceedings were launched in late March, with the dispatch of a “letter of formal notice” requesting further information. The countries are supposed to send a detailed reply within a specified period, usually two months.According to the European Commission, as at the beginning of this month, 11 member states had achieved “full transposition status”.Of the 17 against which infringement procedures have been launched, five had communicated “partial” transposition measures: Bulgaria, Czech Republic, Germany, Latvia and the Netherlands.A further 12 had not communicated any transposition measures: Cyprus, France, Greece, Ireland, Luxembourg, Malta, Poland, Portugal, Romania, Spain, and Sweden. Although Germany’s law to transpose IORP II came into force on the transposition deadline day IPE understands that a regulation was still outstanding as of a couple of weeks ago.In France, meanwhile, the “loi Pacte”, the legislation paving the way for transposition of IORP II, was definitively adopted in parliament last week. It was already clear last year that the country would not meet the IORP II transposition deadline, with a lawyer telling IPE at the time that the risk of a fine seemed limited if transposition was in effect during 2019.In Sweden, the implementation of IORP II has been scheduled to take effect in July.Further reading IORP II: How the EU directive has reshaped the pensions industry IORP II, the European Union’s sweeping reform of pension fund legislation, came into force on 13 January. Here’s how different member states have adapted their national rulebooks. Ireland misses 80% of target dates in pension reform plans The Irish government had failed to deliver on 80% of the deadlines it set out in its pensions roadmap for reform as of the end of January, according to the IAPF. This included a number of changes linked to implementing IORP II.Dutch cross-border questionsIPE’s Dutch sister publication Pensioen Pro asked Commission staff for more information about the infringement case against the Netherlands, but they declined to provide details, citing confidentiality.Hans van Meerten, pensions lawyer and professor of European pensions law at Utrecht University, said he suspected that the infringement procedure was focused on the additional conditions the Dutch government had set for cross-border bulk transfers.Last September, the government amended legislation implementing the directive to introduce higher thresholds for the approval of schemes switching jurisdiction, after it emerged that one scheme’s funding level rose by 11 percentage points since its move from the Netherlands to Belgium.Pieter Omtzigt, MP for the Christian Democrats, received broad support in parliament when he argued that the funding improvement was the result of “supervisory arbitrage”.Cross-border transfers must now be approved by at least two-thirds of a scheme’s membership.Wouter Koolmees, the Dutch minister for social affairs, has insisted that the additional condition is not at odds with European legislation.However, Van Meerten and Erik Lutjens, pensions lawyer and professor of European pensions law at Amsterdam’s Free University, have both suggested that the change was illegal.last_img read more

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USC men’s tennis team tackles the Sherwood Collegiate Cup

first_imgLooking to shake off a rough start to the new year, the defending NCAA champion USC men’s tennis team will try to divide and conquer at the Sherwood Collegiate Cup this weekend. From today through Jan. 19, the Trojans will partake in singles and doubles individual tournaments in Westlake Village, Calif., along with competitors from Baylor, Stanford and UCLA.The USC men’s tennis team collectively struggled in its first tournament of 2015, the Southern California United States Tennis Association Pro Futures Circuit event – senior Eric Johnson was the lone Trojan able to progress beyond the first round of singles competition, only to fall in the second round, and in doubles, the No. 1-ranked senior duo of Roberto Quiroz and Yannick Hanfmann was eliminated in the tournament quarterfinals.Following the USTA Pro Futures Circuit event, head coach Peter Smith cited a lack of match fitness from the holiday layover as a primary factor for his team’s woes.“It’s kind of like waking in the morning and not having your coffee,” Smith said. “That was their introduction to the new year. They woke up and went ‘Oh man. Alright, I do have to play at this level.’ To be honest, they were playing against some top competition, so it was the perfect way to start the new year.”After coming back and turning it up a notch in practice this week, Smith is confident that the defending champion Trojans will return to form at Sherwood during the weekend.“We’re playing much better,” Smith said. “They enjoyed Christmas, what can I say. They’ve gotten into the routine, they’ve gotten their workouts. [The USTA Pro Circuit] put a sense of urgency to their workouts this week, and everyone really played a lot better – a couple levels higher this week.”Of the 32 singles and 16 doubles entries, four individual Trojans and two USC tandems are seeded in the tournament. In singles, Hanfmann earned the No. 1 seed in the competition. Senior Jonny Wang enters as the No. 4 seed, followed by sophomore Nick Crystal at the No. 6 spot and rounded out with Quiroz in the No. 7 ranking. In doubles play, the pair of Hanfmann and Johnson take the No. 2 seed, with the duo of Quiroz and junior Max de Vroome set at the No. 4 spot.The remaining top eight seeds for singles pit Baylor’s Julian Lenz at No. 2, UCLA’s Mackenzie McDonald at No. 4, and Stanford’s Tom Fawcett and David Hsu at No. 5 and No. 8 respectively. UCLA’s team of McDonald and Martin Redlicki top the doubles bracket, while Baylor’s pair of Lenz and Felipe Rios take the No. 3 seed in team competition.“Every time you enter a tournament, you expect it to be as tough as any other,” sophomore Connor Farren said. “I think it’s going to be a great competition, and hopefully we can get better every match.”Last year in the Sherwood Collegiate Cup, then-junior Quiroz reached the singles quarterfinals and then-sophomore Vroome won the consolation tournament in singles play. Quiroz and then-freshman Farren battled their way to the semifinals of last year’s Sherwood doubles tournament.With a team of half underclassmen this year, Smith will use the Cup as a diagnostic for the level at which his players are competing.“A lot of the lineup has been established through the fall season, but it’s a fresh look to see how everyone is playing,” Smith said. “It’s really just to see where everybody’s at on the court.”The team’s freshmen will get their first taste of spring competition this weekend. Freshman Tanner Smith, set to make his regular season debut at Sherwood, feels the longtime powerhouse tennis program has primed him for collegiate competition.“Our seniors are great, they really know how to push us,” Smith said. “It’s just so exciting, being surrounded by so many good players. This [tournament] is going to be fun”Still in the opening stages of the spring season, the Trojans will hope to gain early momentum as they shake off the rust and pursue their sixth NCAA championship in seven years.“When you sign up to come to USC, whether you’re a player or a coach, the tradition here is good and the expectation is to do the best,” Smith said. “But to do that, you have to prepare your best.”last_img read more

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