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One-and-Done Heart Disease Prevention? Scientists Show It May Be Possible.

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One-and-Done Heart Disease Prevention? Scientists Show It May Be Possible.

In a small, preliminary study, an experimental gene-editing treatment dramatically lowered cholesterol levels, perhaps permanently, after just one infusion, scientists reported on Monday.

If confirmed in larger studies, researchers hope the findings may lead to a one-and-done way to prevent heart disease in large numbers of people. Most gene therapies target rare diseases, but cardiovascular disease kills nearly 800,000 Americans a year.

“We have these debates and new guidelines that we should be treating people earlier,” said Dr. John H. P. Alexander, a cardiologist at Duke University who was not involved with the study. “A curative therapy would change the game.”

The study, published in The New England Journal of Medicine, was an interim analysis of 35 patients in a trial that will involve as many as 85 participants. All have genetically high levels of LDL cholesterol — the bad kind — or heart disease.

In the 35 patients, a single infusion of the highest dose of the treatment reduced LDL cholesterol levels by as much as 62 percent. The change has been sustained in a subgroup whose members were treated 18 months ago.

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It will be followed by a larger study of 200 patients.

It is unusual for The New England Journal of Medicine to publish such a preliminary result. But “it looks like it works pretty well,” said Dr. Eric Rubin, the editor in chief. Moreover, he noted, the trial is an ambitious attempt to apply cutting-edge gene therapy to the leading cause of death in the United States.

Still, “we need much more safety data,” said Dr. J. Michael Gaziano, the director of preventive cardiology at the Boston V.A. health care system, who was not involved in the new study. The Food and Drug Administration requires that all patients in gene therapy studies be followed for 15 years.

Patients in the trial received an infusion containing a gene editing “machine,” or a tiny molecular factory wrapped in a cloak of fat. The fat-coated particles travel through the blood directly to the liver, where they are taken up by cells that remove the fatty wrapper.

The editing machine then crawls along the liver cell’s DNA until it finds its target, a gene called PCSK9. It stops there and erases one DNA letter in the gene, replacing it with another.

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That simple change disables the PCSK9 gene and prevents cells from making the PCSK9 protein. Without it, the liver pulls more LDL cholesterol out of the bloodstream, keeping the levels lower.

The study was led by Dr. Sekar Kathiresan, the chief executive at Verve Therapeutics, now a subsidiary of Eli Lilly. Dr. Kathiresan, a cardiologist, said he was motivated by personal history.

His grandmother, father, uncle and brother all had heart attacks. His brother died of cardiac arrest at age 42, just after returning from a run.

Gene therapies for rare diseases carry multimillion-dollar price tags. But Dr. Daniel Skovronsky, chief scientist at Eli Lilly, said that would not be the case if this treatment were eventually approved.

“That’s not what we’re going for here,” he said. “We’re going for a medicine that someday could be part of primary care.”

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High LDL levels are eminently treatable with an array of medicines, including the old standbys, daily statin pills. More recent advances include injected drugs that block the protein made by the PCSK9 gene, creating the same effect as gene editing.

But too many people cannot or will not take the drugs. Between one third and a half of patients stop taking cholesterol-lowering medications within a year of starting them, even people who have had heart attacks.

Kristy Faulkner, 45, who lives in Guilford, Conn., is among those who need treatment but are reluctant to take a powerful drug. Heart disease runs in her family, and she had a heart attack when she was 42.

“There’s some sort of internal denial, like I can’t be on these meds every day of my life,” she said.

“I understand the importance,” she added, “and I feel ashamed.”

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Her cardiologist, Dr. Erica Spatz, at Yale University, is hoping Ms. Faulkner’s insurance will pay for a PCSK9 inhibitor that only has to be administered every six months. Her medical history means there is “no margin for error,” Dr. Spatz said.

But a gene-editing treatment that is administered just once?

“This kind of therapeutic breakthrough could be a game changer for people like her,” Dr. Spatz said.

Alice Thomas, 64, of Lexington, N.C., would love to take cholesterol-lowering drugs but can’t get them. Her sole source of income is Social Security, and while statins are cheap, she was unable to tolerate them.

Her insurance did not approve the injectable drugs that might have helped. She has had two strokes, and a few months ago, her LDL cholesterol level was dangerously high at 190.

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“I didn’t have anything,” Ms. Thomas said. “Then I found out about this study.”

She received the infusion in Dr. Kathiresan’s trial on March 30. Two weeks later, her cholesterol level was 50.

“This is great,” she said. “One time and it’s over.”

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Oliver Tree, musician and Santa Cruz native, dies in helicopter crash

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Oliver Tree, musician and Santa Cruz native, dies in helicopter crash

Oliver Tree, a genre-defying singer-songwriter and Santa Cruz native, was one of six people killed when two helicopters collided Sunday morning in Brazil, according to the Associated Press. He was 32.

Tree, a quirky artist known for his highly theatrical music videos and crisp bowl cut, had been traveling through South America as a part of his world tour. CNN Brazil reported Argentinian YouTuber Gaspar Prim, also known as Gaspi, was among those killed in the crash.

The mid-air collision occurred in Rio de Janeiro, with one of the helicopters landing in the parking lot of a car dealership, the AP reports. Local authorities have launched an investigation into the cause of the crash.

Tree, born Oliver Tree Nickell, broke out in the electronic music world first performing as, simply, Tree. He released an e.p., “Demons,” in 2013, which included a cover of Radiohead’s “Karma Police” that caught the ear of Thom Yorke. He later attended CalArts north of Los Angeles, and signed to Atlantic Records for his major-label debut e.p. “Alien Boy” in 2018.

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To find his distinct look, he told the Santa Cruz Sentinel that “I was making a statement with it. Everybody’s trying to look so beautiful and sexy nowadays. It was my way of rebelling against that. So, I tried to make myself look as silly and ridiculous as possible.”

Tree was an instant hit on the festival circuit for his outlandish stage productions and outsider charisma, performing at Lollapalooza, Coachella and Outside Lands. He collaborated with Skrillex, David Guetta and Zeds Dead, and was fiercely protective of his meticulously weird visual identity and video concepts, telling Rolling Stone that “That’s kind of my signature. The people who do f- with me know me because of my videos..Music is my day job but my real dream is to be making feature films.

He released his major label debut LP, “Ugly Is Beautiful,” in 2020. His hit song “Life Goes On” and collaboration “Miss You” with German DJ Robin Schulz earned him international recognition and climbed onto the Billboard Hot 100. He released four full length albums as Oliver Tree, most recently April’s independent LP “Love You Madly Hate You Badly.”

Tree had performed in Buenos Aires on June 4.

From July to October, he had shows scheduled throughout Europe, Australia and China. This year, he performed at the Coachella Valley Music and Arts Festival this year as a special guest of electronic producer Subtronics. In one of his last social media posts, he made a point to spotlight an upcoming show on Aug. 9 in his hometown at the Quarry Amphitheater at UC Santa Cruz.

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“I can’t believe Oliver is gone,” Schulz posted on Instagram. “You were such a lovely soul and a one of a kind character. Working with you on ‘Miss You’ was an honor. My deepest condolences to his family, friends and everyone who loved him.”

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New MLK hospital program brings amputations to zero for at-risk diabetic patients

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New MLK hospital program brings amputations to zero for at-risk diabetic patients

More than three decades after a diagnosis of Type 2 diabetes, Michelle Caldwell says her disease is better controlled than ever.

She keeps regular appointments with her endocrinologist, primary care provider, dietician and pharmacist at MLK Community Medical Group, the outpatient arm of MLK Community Healthcare.

She picks up weekly produce deliveries in the South Los Angeles hospital’s cafeteria and attends its occasional cooking classes. She has learned to decode nutrition labels and developed a taste for salads and nuts.

Just one hurdle remains: the shoes.

Diabetes can damage foot nerves, making it easier for patients to miss small scratches and wounds that could lead to serious infections. Her care team was gently urging her to switch to supportive, closed-toe footwear.

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But Caldwell loves a sandal, and the podiatrist-approved options were crimping her style.

“It doesn’t have to be, like, fashion fashion,” she said with a laugh during a recent visit with primary care provider Dr. Edward Cardenas at his East Compton office. But were there any options that didn’t look like “Frankenstein feet”?

That down-to-the-toes level of care is a feature of a program that has transformed the way MLK Community Healthcare treats diabetes, a chronic condition that affects one in every six South Los Angeles residents and nearly a quarter of MLK’s outpatients.

Four years after MLK launched an intensive management program for the most at-risk patients, more than 80% of enrollees have seen blood sugar levels decline. More than 70% have brought their blood pressure under control.

And diabetic-related amputations — which are painful and life-altering procedure that were the hospital’s most common surgery for years — have plummeted to zero for program patients.

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No novel medications or treatments are behind these results, said Dr. Jorge Reyno, MLK’s senior vice president for population health.

Dr. Edward Cardenas examines a patient with diabetes.

(Christina House / Los Angeles Times)

Rather, a relatively modest one-time grant has allowed the hospital system — whose service area includes some of L.A.’s poorest and most disadvantaged neighborhoods — to provide the same level of care for its diabetic patients that people in wealthier areas would expect as standard.

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“What we’ve demonstrated here is that we can get best-in-class care — we can even beat national benchmarks for care — if there’s the appropriate commitment and investment. And that people’s health doesn’t have to be determined just by their zip code,” Reyno said. “Because what we’ve created here is not necessarily incredibly innovative. It’s just what needs to be available — and is available in other locations.”

Some 1.3 million people live in MLK’s South Los Angeles service area. More than 90% are Black or Latino, and nearly 70% are either uninsured or have health coverage through Medi-Cal, Medicare or both.

Medi-Cal’s low provider payment rates is one reason South L.A. has only one-third of the full-time physicians necessary to treat a population of its size — a 1,500-doctor shortage, according to MLK’s research.

For many locals, MLK’s emergency department is about the only place they can see a doctor, given the challenge they face securing a timely appointment with a physician who accepts their health coverage.

Roughly 123,000 patients arrived last year at the hospital’s emergency department, which was designed to treat 40,000 people annually. About 40% were seeking primary care.

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Emergency room physicians were diagnosing diabetes in severely ill people who did not know they had the disease and treating life-threatening complications for those whose disease had long gone unmanaged.

Patients arrived with gangrenous foot wounds that harried providers elsewhere brushed off as athlete’s foot. Rates of diabetic ketoacidosis, a life-threatening complication that occurs when insulin levels are so low that cells can no longer convert glucose into energy, were three times that of the rest of Los Angeles County.

For many, care arrived too late to prevent one of the disease’s most serious complications: amputation.

Nerve damage means a blister or pebble in the shoe can go unnoticed until it creates a serious wound. High blood sugar impairs immune function and narrows vessels that carry oxygen-rich blood, making it harder for skin to heal. Once serious infection sets in, amputating a foot or limb may be the only option to save a patient’s life. Across the U.S., diabetes complications are responsible for roughly 80% of all non-trauma related amputations, according to the Centers for Disease Control and Prevention.

Broaching amputation with a patient “is really tough,” Cardenas said. “You’re taking such a big part of them away. It’s identity, it’s confidence, it’s [the] ability to walk and do things for themselves. It’s a huge, huge thing.”

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It’s also costly. Diabetes cost $306.6 billion in U.S. direct medical spending in 2022, the most recent year for which numbers are available, and foot ulcer-related issues were responsible for about one-third of that, said Dr. David G. Armstrong, director of USC’s limb preservation program and the Southwestern Academic Limb Salvage Alliance.

Indirect costs are also steep. One study of post-surgery outcomes found that only about one-third of patients were able to return to work after the amputation surgery, despite an average age of 54.

“The economic ramifications aren’t just the fact that you’re not working. It’s also that people in your family are taking off of work to be able to help accommodate this, or having to provide extra resources that they previously weren’t having to, so it has sort of a multi-generational effect,” said Dr. Caitlin Hicks, a vascular surgeon and director of research at Johns Hopkins University’s Multidisciplinary Diabetic Foot and Wound Clinic.

In California, the households most likely to bear that cost are those that can least afford it.

Diabetic residents in MLK’s service area and other economically impoverished parts of California were more than 10 times more likely to have a toe, foot or leg amputated than diabetic people in more affluent areas, according to one 2014 UCLA study.

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“The finding that residents living in lower income areas bear a disproportionate share of disability and disfigurement from amputations is deeply disturbing in a society that espouses equality and outspends all other nations on health care for its more affluent citizens,” the paper’s authors wrote.

It was a problem MLK decided to do something about.

A health worker in a white lab coat talks with a patient.

Clinical Nutrition Manager Jackie Juarez, left, chats with Claudette Meeks, a member of the community and a hospital patient, following a cooking class at MLK Community Hospital.

(Christina House / Los Angeles Times)

The hospital secured a $2 million grant from the Good Hope Medical Foundation, a private foundation based in Pasadena, with additional funding from the Rose Hills Foundation and L.A. Care Health Plan.

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In October 2021, it began officially enrolling patients in its Diabetes Management Center of Excellence. Within this was an intensive-management program for a subset of high-risk patients, including those with Type 1 diabetes, gestational diabetes or hemoglobin A1C levels — an indicator of blood sugar — at 9.0% or more. (For people without diabetes, a level below 5.7% is considered normal.)

For the most part, the system already had the endocrinologists, nephrologists and primary care physicians it needed. The money let MLK build a network of dedicated support staff who could take care of diabetic patients outside the exam room.

Between visits, patients in the intensive-management program had access to a clinical care pharmacist who reviewed and coordinated medications; a diabetes educator who walked them through blood sugar monitoring, meal planning and other daily concerns; community health workers who could make home visits; and a nurse care manager who served as their primary advocate and point of contact.

Through the hospital’s Recipes for Health program, they could pick up weekly bundles of fresh produce and take bimonthly classes on diabetic-friendly recipes.

They were more likely to stick to their treatment plan, and had more time at doctor visits to discuss medical issues.

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A man holds a slice of cake on a plate.

Diabetes patient Jose Magallanes tries a cheesecake during a cooking class at MLK Community Hospital.

(Christina House / Los Angeles Times)

“We have multiple people reaching out and interacting with the patients in between physician visits,” said MLK endocrinologist Dr. Megan Jacobs. “They have someone reaching out to them [and] talking to them about the social aspects of things — how they have to take into account their diabetes when they go out to dinner and when they’re at a party.”

By year three, 66% of patients in the intensive-management program had lower blood sugar levels than they did at enrollment; by the fourth year, 81% did. In the third year 63% of patients had brought their blood pressure under control, rising to 71% the following year.

Four years after the program started, appointment compliance hit 84%, up from 50% at baseline. The hospital’s most severely diabetic patients were hospitalized for diabetes at less than half the rate of the area’s general population.

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Most significantly, amputations among the intensive-management group dropped to virtually zero.

Over the course of four years, only one of the 1,165 patients in the high-risk group required an amputation. The surgery took place less than a month after their enrollment, indicating they likely entered the program with a wound at critical levels.

Diabetic-related amputations and wound care are now MLK’s third-most common type of surgical procedures, after holding the top spot since the hospital’s 2015 opening.

“This is absolutely, positively spectacular,” USC’s Armstrong said of MLK’s results. “This is life affirming stuff.”

The primary grant ends next year. After that, the program’s future is uncertain.

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MLK is eligible to reapply to the Good Hope Medical Foundation, which has been “very happy” with the program’s outcomes, said Howard A. Kahn, the foundation’s chair.

The hospital is also talking to L.A. Care, the largest publicly operated health plan in the U.S., about a potential partnership, Reyno said. It could be a win for both sides.

“The benefit of cost savings usually goes to the state Medicaid plan or to the insurance carrier, who doesn’t have as high a cost to pay,” Reyno said. “If a program like this could be replicated in other safety net communities and have a wider impact, then certainly the return on investment would be even greater.”

Care providers also said they see improvements the data doesn’t capture.

“I hear [patients] say, ‘Oh, I walked to the park with my grandchildren,’ or ‘I was able to move around because I’ve lost the weight’ … maybe they had a sore on their foot that was kind of questionable, [and] ‘Now it’s healed because my sugars are under control,” said nurse care manager Monica Garcia. “Just seeing the benefits when they are compliant is the satisfaction.”

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Back at the clinic office in East Compton — the shoe issue set aside for now — Cardenas examined Caldwell’s feet and lower limbs.

The doctor was optimistic that Caldwell’s recent discomfort came from tight muscles, rather than nerve damage, and recommended a stretching and strengthening regimen.

“It shouldn’t be painful, just like a tug,” he said, demonstrating a standing calf stretch. “If you like, I can refer you to physical therapy as well.”

Having providers take the time to explain her disease, rather than just scribbling out prescriptions, has made a world of difference for Caldwell, she said.

“It’s an awesome experience. I’ve changed my eating habits, I’m learning to read labels more clearly,” she said. “Even at my age, you think you know, but you don’t know.”

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NorCal braces for dry, dangerous fire season as SoCal faces typical conditions

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NorCal braces for dry, dangerous fire season as SoCal faces typical conditions

Southern California’s top fire officials met behind closed doors in East Los Angeles Friday to discuss the outlook for this year’s peak fire season and how to coordinate the region’s world-class firefighters to keep communities safe.

At a press conference afterward, officials stressed that even though coastal Southern California is not expected to have an exceptionally dangerous fire season, they are doing everything they can to protect Californians. They urged residents to do the same.

“It is clear that wildfires are no longer solely a fire-service problem. They are an all-of-us problem,” said Orange County Fire Authority Interim Chief T.J. McGovern, standing in front of a suite of emergency response vehicles at L.A. County Fire Department’s headquarters. “They can only be mitigated by all of us working together.”

Coastal Southern California, which had the third-wettest season in record within the last 15 years, can expect a typical wildfire season, fire weather analysts predict. That’s in sharp contrast to Northern California, which saw a record-breaking March heat wave melt mountain snowpack early. Fire officials typically rely on the snowpack to keep vegetation green and moist into summer.

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“The interesting thing about last year is that it was the southern half of the state that was significantly drier,” said Cal Fire Director Joe Tyler at a wildfire season outlook briefing last month. This year, he said, “we’re seeing that critical condition really spreading across Northern California.”

Coastal Southern California must still endure a particularly dry June before reaching typical conditions July through September — and even “typical” conditions remain dangerous, which is why officials urged Southern Californians Friday to remain vigilant.

A series of fires mid-May served as a warning shot for the region. The Sandy fire in Ventura County destroyed one home and damaged two more structures. The Santa Rosa Island fire burned through a third of the second-largest Channel island.

Officials at Friday’s Southern California meeting urged homeowners to do what they can to harden their homes against wildfire — including covering vents with mesh to prevent embers from entering the home and using multi-paned tempered windows that are less likely to shatter in extreme heat.

They also asked homeowners to maintain defensible space around homes by clearing dead vegetation in their yards, making sure there is space between shrubs and trees and creating a 5-foot buffer around homes with nothing combustible, including plants.

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Homeowners should also make sure they’re signed up for evacuation alerts from their local fire department, the chiefs added, and should not hesitate to evacuate at the sight or smell of smoke — regardless of whether an official evacuation has been ordered.

As for their part, Southern California fire departments have been working to thin out hazardous vegetation surrounding communities and remain at the ready to respond to fires.

“We will show up. We show up every time, across every jurisdiction … That’s not a question,” said Los Angeles City Fire Department Chief Jaime Moore. However, without defensible space at individual homes, it is “very difficult for us to be able to combat those fires.”

The Los Angeles and Ventura county fire departments have been working to remove flammable vegetation surrounding communities in the Santa Monica Mountains with fire department crews, goats and prescribed fire. The U.S. Forest Service has been doing similar work in the San Gabriel Mountains.

The crews are working to create a network of vegetation-free pathways, called fuel breaks, that can slow fires and give firefighters strategic access to wildlands to combat blazes. They are also working to remove particularly flammable invasive grasses.

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“As we share our preparation to defend communities and build wildfire resilience, it’s a call to action,” Angeles National Forest Fire Chief Robert Garcia said. “It’s now a shift to individual homeowners and communities to start leveraging some of that work that your agencies are doing.”

While this kind of landscape-wide work has significantly increased in the state over the past five years, California is running out of money to complete such projects.

Meanwhile, the U.S. Forest Service saw a decrease in how much work it could complete after the Trump administration significantly reduced the size of the service’s workforce.

Neither the state’s funding woes nor the shrinking of the federal workforce are expected to impact firefighting ability.

“It is absolutely as strong as ever,” Tyler said last month of the federal and state government’s ability to respond to fires.

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