In a milestone year, gene therapy finds a place in medicine

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In a milestone year, gene therapy finds a place in medicine

2017-12-29 11:09 Last Updated At：18:11

After decades of hope and high promise, this was the year scientists really showed they could doctor DNA to successfully treat diseases. Gene therapies to treat cancer and even pull off the biblical-sounding feat of helping the blind to see were approved by U.S. regulators, establishing gene manipulation as a new mode of medicine.

Almost 20 years ago, a teen's death in a gene experiment put a chill on what had been a field full of outsized expectations. Now, a series of jaw-dropping successes have renewed hopes that some one-time fixes of DNA, the chemical code that governs life, might turn out to be cures.

"I am totally willing to use the 'C' word," said the National Institutes of Health's director, Dr. Francis Collins.

Gene therapy aims to treat the root cause of a problem by deleting, adding or altering DNA, rather than just treating symptoms that result from the genetic flaw.

The advent of gene editing — a more precise and long-lasting way to do gene therapy — may expand the number and types of diseases that can be treated. In November, California scientists tried editing a gene inside someone's body for the first time, using a tool called zinc finger nucleases for a man with a metabolic disease. It's like a cut-and-paste operation to place a new gene in a specific spot. Tests of another editing tool called CRISPR, to genetically alter human cells in the lab, may start next year.

"There are a few times in our lives when science astonishes us. This is one of those times," Dr. Matthew Porteus, a Stanford University gene editing expert, told a Senate panel discussing this technology last month.

It's a common path for trail-blazing science — success initially seems within reach, setbacks send researchers back to the lab, new understandings emerge over years, and studies ultimately reveal what is safe and effective.

Here is a look at what's been achieved and what lies ahead.

A STRING OF FIRSTS

The year started with no gene therapies sold in the U.S. and only a couple elsewhere. Then the Food and Drug Administration approved the first CAR-T cell therapies, which alter a patient's own blood cells to turn them into specialized cancer killers. They're only for certain types of leukemia and lymphoma now, but more are in the works for other blood cancers.

Last week, the FDA approved Luxturna, the first gene therapy for an inherited disease, a form of blindness. People with it can't make a protein needed by the retina, tissue at the back of the eye that converts light into signals to the brain, enabling sight. The therapy injects a modified virus containing a corrective gene into the retina so the cells can make the protein.

Children who received the treatment told what it was like to gain vision.

"Oh yikes, colors. Colors are super fun," said 13-year-old Caroline Carper of Little Rock, Arkansas. "And the sunshine is blinding."

Gene therapies also showed some promise against a variety of diseases including hemophilia, a blood clotting problem; "bubble boy" disease, where a flawed immune system leaves patients vulnerable to fatal infections, and sickle cell disease, a serious and painful blood disorder common among black people.

It's not all good news, though. The therapies don't work for everyone. They're shockingly expensive. And no one knows how long some results will last, though scientists say the aim is a one-time repair that gets at the root cause.

"The whole promise ... is to cure diseases. It's based on the rationale of fixing the problem," not just improving treatment, said Dr. Carl June, a University of Pennsylvania scientist who pioneered CAR-T therapy.

A NEW FRONTIER: GENE EDITING

In mid-November, Brian Madeux, a 44-year-old Phoenix man with a metabolic disease called Hunter syndrome, had just become the first person to try an experimental gene editing treatment.

"I believe in science," he texted The Associated Press after doctors sent viruses containing a corrective gene and an editing tool through an IV into his body. The hope is that the gene and the editing tool would enter some of his liver cells and insert the instructions needed to start making an enzyme he lacks.

It's not known yet if it worked. Sangamo Therapeutics is testing its therapy in several studies, and independent monitors will help decide when results are released.

"It's a pretty exciting milestone," Collins said, because it shows a way to treat more diseases than ones that can be addressed now by altering blood cells in the lab or injecting genes into the eye.

"You can imagine having a scalable approach to thousands of genetic diseases," he said.

WHAT'S NEXT

Top of Collins' list: muscular dystrophy and sickle cell.

There's been so much progress that the NIH has modified an oversight panel that just a few years ago reviewed every gene therapy experiment in the U.S. Most are considered safe enough to go ahead without the Recombinant DNA Advisory Committee's review. The panel hasn't even met for a year.

When the panel was formed decades ago, "there was a lot of concern that a graduate student could take some of this home and create a monster in his basement," said one panel member, Boston scientist Dr. Howard Kaufman.

Those fears have eased, he said.

"There's no monsters that have materialized from this."

Tabloid publisher says he pledged to be Trump campaign's 'eyes and ears' during 2016 race

2024-04-24 09:25 Last Updated At：09:30

NEW YORK (AP) — A veteran tabloid publisher testified Tuesday that he pledged to be Donald Trump 's “eyes and ears" during his 2016 presidential campaign, recounting how he promised the then-candidate that he would help suppress harmful stories and even arranged to purchase the silence of a doorman.

The testimony from David Pecker was designed to bolster the prosecution's premise of a decades-long friendship between Trump and the former publisher of the National Enquirer that culminated in an agreement to give the candidate's lawyer a heads-up on negative tips and stories so they could be quashed.

The effort was a way to illegally influence the election, prosecutors have alleged in striving to elevate the gravity of the history-making first trial of a former American president and the first of four criminal cases against Trump to reach a jury. The presumptive Republican presidential nominee in this year's race faces 34 felony counts of falsifying business records in connection with hush money payments meant to stifle embarrassing stories from surfacing in the final days of the 2016 campaign.

With Trump sitting just feet away in the courtroom, Pecker, the first witness, detailed his behind-the-scenes role in Trump's rise from political novice to the Republican nomination and the White House. He explained how he and the National Enquirer parlayed rumor-mongering into splashy tabloid stories that smeared Trump's opponents and, just as crucially, leveraged his connections to suppress seamy stories about Trump, including a porn actor's claim of an extramarital sexual encounter years earlier.

Pecker traced the origins of their relationship to a 1980s meeting at Trump's Mar-a-Lago estate in Palm Beach, Florida, and said the friendship bloomed alongside the success of the real estate developer's TV show “The Apprentice" and the program's subsequent celebrity version.

Their ties were solidified during a pivotal August 2015 meeting at Trump Tower involving Trump, his lawyer and personal fixer Michael Cohen, and another aide, Hope Hicks, in which Pecker was asked what he and the publications he led could do for the campaign.

Pecker said he volunteered to publish positive stories about Trump and negative stories about his opponents. But that wasn't all, he said, telling jurors how he told Trump: “I will be your eyes and ears.”

“I said that anything I hear in the marketplace, if I hear anything negative about yourself, or if I hear anything about women selling stories, I would notify Michael Cohen," so that the rights could be purchased and the stories could be killed.

“So that they would not get published, you mean?” asked prosecutor Joshua Steinglass.

“So that they would not get published, yes” Pecker replied.

To illustrate their point, prosecutors displayed a screenshot of various flattering headlines the National Enquirer published about Trump, including “Donald Dominates!’ and “World Exclusive: The Donald Trump Nobody Knows.” The jury was also shown disparaging and outlandish stories about Trump's opponents, including surgeon Ben Carson and Republican Sen. Marco Rubio.

Pecker painted Cohen as a shadow editor of the National Enquirer’s pro-Trump coverage, directing the tabloid to go after whichever Republican candidate was gaining momentum.

“I would receive a call from Michael Cohen, and he would direct me and direct Dylan Howard on which candidate and which direction we should go,” Pecker said, referring to the tabloid's then-editor.

Pecker said he underscored to Howard that the agreement with the Trump operation was “highly, highly confidential.” He said he wanted the tabloid’s bureau chiefs to be on the lookout for any stories involving Trump and said he wanted them to verify the stories before alerting Cohen.

“I did not want anyone else to know about this agreement I had and what I wanted to do,” the ex-publisher added.

Cohen pleaded guilty in 2018 to federal charges related to his role in the hush money payments. He was once a confidant of Trump's, but their relationship deteriorated in spectacular fashion. Cohen is expected to be a star government witness, and he routinely posts profane broadsides against Trump on social media.

Trump's lawyers are expected to make attacks on Cohen's credibility a foundation of their defense, but in opening with Pecker, prosecutors hoped to focus attention on a witness with a less volatile backstory. Besides maintaining that Trump is innocent, Trump lawyer Todd Blanche told jurors that Cohen cannot be trusted and has “an obsession with getting Trump.”

Pecker's testimony Tuesday followed a hearing earlier in the day in which prosecutors urged Judge Juan M. Merchan to hold Trump in contempt and fine him $1,000 for each of 10 social media posts that they say violated an earlier gag order barring attacks on witnesses, jurors and others involved in the case.

Merchan did not immediately rule, but he seemed skeptical of defense arguments that Trump was merely responding in his posts to others' attacks and had been trying to comply with the order.

Prosecutors allege that Trump sought to illegally influence the 2016 race through a practice known in the tabloid industry as “catch-and-kill” — catching a potentially damaging story by buying the rights to it and then killing it through agreements that prevent the paid person from telling the story to anyone else.

In this case, that included a $130,000 payment to porn actor Stormy Daniels to silence her claims of an extramarital sexual encounter that Trump denies. Prosecutors also described other arrangements, including one that paid a former Playboy model $150,000 to suppress claims of a nearly yearlong affair with the married Trump, which Trump also denies.

In another instance, Pecker recounted a $30,000 payment from the National Enquirer to a Trump Tower doorman for the rights to a rumor that Trump had fathered a child with an employee at Trump World Tower. The tabloid concluded the story was not true, and the woman and Trump have denied the allegations.

As Pecker described receiving the tip in court, Trump shook his head.

Pecker said upon hearing the rumor, he immediately called Cohen, who said it was “absolutely not true” but that he would look into whether the people involved had indeed worked for Trump’s company.

“I made the decision to buy the story because of the potential embarrassment it had to the campaign and Mr. Trump,” Pecker said.

When he told Cohen, Pecker said he thanked him, "And he said that the boss would be very pleased.”

Asked by the prosecutor who he understood the boss to be, Pecker replied: “Donald Trump.”

Explaining why he decided to have the National Enquirer foot the bill, Pecker recalled telling Cohen: “This can be a very big story. I believe it's important that it be removed from the marketplace.”

If he published the story, Pecker said it would be “probably the biggest sale of the National Enquirer since the death of Elvis Presley.”

Jurors viewed an internal Enquirer email and invoice describing the payments to the doorman to kill his story. One document describes the funds coming from the publication’s “corporate” account. An invoice references an “immediate” $30,000 bank transfer payment for “‘Trump’ non-published story.”

Trump's 34 felony counts arise from reimbursements that prosecutors say Trump's company made to Cohen for hush money payments and that were falsely recorded as legal expenses.

The charges are punishable by up to four years in prison, though it’s unclear whether Merchan would seek to put him behind bars. A conviction would not preclude Trump from becoming president again, but because it is a state case, he would not be able to pardon himself if found guilty. He has repeatedly denied any wrongdoing.

Testimony resumes on Thursday.

Tucker reported from Washington. Associated Press writer Jill Colvin in New York contributed to this report.

Follow the AP's coverage of former President Donald Trump at https://apnews.com/hub/donald-trump.

In a milestone year, gene therapy finds a place in medicine

TECH

In a milestone year, gene therapy finds a place in medicine

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