Health
Mutated DNA Restored to Normal in Gene Therapy Advance
Researchers have corrected a disease-causing gene mutation with a single infusion carrying a treatment that precisely targeted the errant gene.
This was the first time a mutated gene has been restored to normal.
The small study of nine patients announced Monday by the company Beam Therapeutics of Cambridge, Mass., involved fixing a spelling error involving the four base sequences — G, A, C and T — in DNA. The effect was to change an incorrect DNA letter to the right one. The result was a normal gene that functioned as it should, potentially halting liver and lung damage of patients with a rare disorder.
“This is the beginning of a new era of medicine,” said Dr. Kiran Musunuru, a gene therapy researcher at the University of Pennsylvania’s Perelman School of Medicine.
He added that the method offers the hope of treating other genetic diseases precisely by fixing mutations — an alternative to current gene therapies, which either add new genes to compensate for mutated ones, or slicing DNA to silence genes.
Dr. Musunuru is a co-founder and equity holder of Verve Therapeutics, a gene therapy company, and receives funding from Beam Therapeutics for research, but not for this study.
Dr. Richard P. Lifton, president of Rockefeller University and head of its Laboratory of Human Genetics and Genomics, said the sort of gene editing Beam did, rewriting genes with an infusion, “is a holy grail” that “has the promise for being a one-and-done kind of therapy.”
Dr. Lifton is a director of Roche Pharmaceuticals and its subsidiary Genentech.
Despite the study’s small size, he said the results are “a very impressive advance and very promising.”
The study involved patients who have alpha-1 antitrypsin deficiency, or AATD, a genetic disease that affects an estimated 100,000 Americans, mostly of European ancestry. That makes it as common as sickle cell in this country. It is progressive and incurable.
The alpha-1 antitrypsin protein is made in the liver and normally goes to the lungs and protects them from inflammation from inhaled irritants like smoke or dust. But in people with the disease, a single change in a DNA letter in the gene results in a misshapen and nonfunctional protein. The result is often emphysema or chronic obstructive pulmonary disease in unprotected lungs.
But many of the aberrant alpha-1 antitrypsin proteins never get to the lungs and instead build up in patients’ livers, often causing cirrhosis.
The gene editing was simple for patients. They sat in a chair for a couple of hours while lipid nanoparticles, like those used in Covid vaccines, were infused into their blood. The nanoparticles did not hold vaccines, though. Instead, they encased a microscopic gene editor. The lipid casing protected the editor on a journey to the liver.
When the nanoparticles reached the liver, the lipid layer peeled off, releasing the editor — a disabled CRISPR molecule that acted like a GPS for the genome and an enzyme to fix the mutation. The CRISPR molecule crawled along the patient’s DNA until it found the one incorrect letter that needed to be repaired among the three billion DNA letters in the genome. Then the editing enzyme replaced that letter with the correct one.
The study divided the patients into three groups and tested three different doses of the gene editor. Those who got the highest dose made enough normal alpha-1 antitrypsin to be in a range where no more damage should occur. There were no serious side effects, said John Evans, Beam’s chief executive officer.
Beam will now be offering the higher dose to the patients who got the lower doses in the company’s study. Beam will also study the treatment in more patients, and test an even higher dose of its gene editor.
“And then we immediately have to think about how we can get this approved,” Mr. Evans said.
Dr. Noel McElvaney, a professor at the Royal College of Surgeons in Ireland and an investigator in the Beam study, said there’s a real need for an effective treatment to halt the damage done by the mutated gene. He said he sees patients in their 30s and 40s with severe emphysema and “really bad liver disease.” And, he said, “by the time we see them there is already a significant amount of damage.”
For those suffering the worst effects of AATD, he said, the new gene therapy is “a major major breakthrough.”
“The big pro” of the new treatment, he said, is that “it theoretically cures the liver and lung disease in one go.”
Dr. McElvaney added, though, that “like all genetic interventions, we have to follow up for a long time to make sure it’s as good as we think it is.”
But patients now have renewed hope, said Dr. Andrew Wilson, scientific director of the Alpha-1 Foundation, an advocacy group.
“We have been dreaming of gene therapy as a treatment for this disease,” he said.
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Health
Alzheimer’s prevention breakthrough found in decades-old seizure drug
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A drug that has long been used to treat seizures has shown promise as a potential means of Alzheimer’s prevention, a new study suggests.
The anti-seizure medication, levetiracetam, was first approved by the FDA in November 1999 under the brand name Keppra as a therapy for partial-onset seizures in adults. The approval has since expanded to include children and other types of seizures.
Northwestern University researchers recently found that levetiracetam prevented the formation of toxic amyloid beta peptides, which are small protein fragments in the brain that are commonly seen in Alzheimer’s patients.
The medication was found to prevent the formation of amyloid-beta 42 in both animal models and cultured human neurons, according to the study findings, which were published in Science Translational Medicine.
The effect was also seen in post-mortem human brain tissue obtained from individuals with Down syndrome, who are at high risk for Alzheimer’s disease.
The medication was found to prevent the formation of amyloid-beta 42 in both animal models and cultured human neurons. (iStock)
“While many of the Alzheimer’s drugs currently on the market, such as lecanemab and donanemab, are approved to clear existing amyloid plaques, we’ve identified this mechanism that prevents the production of the amyloid‑beta 42 peptides and amyloid plaques,” said corresponding author Jeffrey Savas, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine, in a press release.
“Our new results uncovered new biology while also opening doors for new drug targets.”
HIDDEN BRAIN CONDITION MAY QUADRUPLE DEMENTIA RISK IN OLDER ADULTS, STUDY SUGGESTS
The brain is better able to avoid the pathway that produces toxic amyloid‑beta 42 proteins in younger years, but the aging process gradually weakens that ability, Savas noted.
“This is not a statement of disease; this is just a part of aging. But in brains developing Alzheimer’s, too many neurons go astray, and that’s when you get amyloid-beta 42 production,” he said.
The effect was also seen in post-mortem human brain tissue obtained from individuals with Down syndrome, who are at high risk for Alzheimer’s disease. (iStock)
That then leads to tau (“tangles”) — abnormal clumps of protein inside brain neurons — which can kill brain cells, trigger neuroinflammation and lead to dementia.
In order for levetiracetam to function as an Alzheimer’s blocker, high-risk patients would have to start taking it “very, very early,” Savas said — up to 20 years before elevated amyloid-beta 42 levels would be detected.
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“You couldn’t take this when you already have dementia, because the brain has already undergone a number of irreversible changes and a lot of cell death,” the researcher noted.
The researchers also did a deep dive into previous human clinical data to determine whether Alzheimer’s patients who were taking the anti-seizure drug had slower cognitive decline. They reported that the patients in that category had a “significant delay” in the span from cognitive decline to death compared to those not taking the drug.
“This analysis supports the positive effect of levetiracetam to slow the progression of Alzheimer’s pathology,” the researcher said. (iStock)
“Although the magnitude of change was small (on the scale of a few years), this analysis supports the positive effect of levetiracetam to slow the progression of Alzheimer’s pathology,” Savas said.
Looking ahead, the research team aims to find people who have genetic forms of Alzheimer’s to participate in testing, Savas said.
Limitations and caveats
The study had several limitations, including that it relied on animal models and cultured cells, with no human trials conducted.
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Because the study was observational in nature, it can’t prove that the medication caused the prevention of the toxic brain proteins, the researchers acknowledged.
Savas noted that levetiracetam “is not perfect,” cautioning that it breaks down in the body very quickly.
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The team is currently working to create a “better version” that would last longer in the body and “better target the mechanism that prevents the production of the plaques.”
“You couldn’t take this when you already have dementia, because the brain has already undergone a number of irreversible changes and a lot of cell death.”
The medication’s common documented side effects include drowsiness, weakness, dizziness, irritability, headache, loss of appetite and nasal congestion.
It has also been linked to potential mood and behavior changes, including anxiety, depression, agitation and aggression, according to the prescribing information. In rare cases, it could lead to severe allergic reactions, skin reactions, blood disorders and suicidal ideation.
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Funding for the study was provided by the National Institutes of Health and the Cure Alzheimer’s Fund.
Fox News Digital reached out to the drug manufacturer and the researchers for comment.
Health
Seniors over 80 who eat specific diet may be less likely to reach 100 years old
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Older adults who avoid meat in their golden years may be less likely to reach age 100 than their meat-eating counterparts, new research suggests.
Researchers tracked more than 5,000 adults aged 80 or older who were enrolled in the Chinese Longitudinal Healthy Longevity Survey.
Between 1998 and 2018, data showed that those who did not eat meat were less likely to reach their 100th birthday than those who consumed animal products regularly.
The findings seem to contradict previous studies that have linked vegetarianism and plant-based diets to lower risks of heart disease, stroke, diabetes and obesity.
Most evidence supporting the benefits of plant-based diets comes from studies tracking younger populations, the researchers noted.
The findings contrast with previous research praising plant-based diets for their positive influence on heart health. (iStock)
The study, published in The American Journal of Clinical Nutrition, points to losses in muscle mass and bone density with age, shifts that can increase the risk of malnutrition and frailty in the “oldest old.”
As people enter their 80s and 90s, the nutritional priority often shifts from preventing long-term chronic diseases to maintaining day-to-day physical function, experts say.
HOW MUCH RED MEAT IS TOO MUCH? EXPERTS WEIGH IN ON FOOD PYRAMID UPDATES
“The headline ‘vegetarians over 80 less likely to reach 100’ sounds surprising, because it contrasts with decades of data linking plant‑forward diets to lower chronic disease risk earlier in life,” Erin Palinski-Wade, a New Jersey-based registered dietitian, told Fox News Digital.
“However, once you see that this research is limited to adults over the age of 80 who are also underweight — and that this link disappears with the consumption of eggs, dairy and fish — the results are less surprising.”
While diets earlier in life tend to emphasize avoiding long-term disease, older age necessitates nutrients and weight maintenance, experts say. (iStock)
In those over 80, restricting animal proteins may be less likely to promote longevity, according to Palinski-Wade, who was not involved in the study.
Eliminating all animal protein — particularly in a population that may already experience diminished hunger cues — can make it more difficult to meet adequate protein needs, potentially increasing the risk of nutrient deficiencies, the nutritionist said.
ALZHEIMER’S SYMPTOMS COULD BE PREDICTED YEARS IN ADVANCE THROUGH ONE SIMPLE TEST
In addition to a higher tendency to be underweight, older populations also face a greater risk of bone fractures due to lower calcium and protein intake.
Potential limitations
The lower rate of vegetarians reaching 100 was only observed in participants identified as underweight, the researchers noted. No such association was found in people who maintained a healthy weight.
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Because being underweight is already linked to greater frailty and mortality risk, the researchers noted that body weight may partly explain the findings, making it difficult to determine whether diet itself played a direct role.
Those incorporating animal-sourced products other than meat were just as likely to live to 100. (iStock)
Additionally, the shortened lifespans were not found in people who continued to eat non-meat animal products, such as fish, dairy and eggs.
Older adults with these more flexible diets were just as likely to live to 100 as those eating meat, as these foods may provide the nutrients necessary for maintaining muscle and bone health, the researchers noted.
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“This is an observational study, so it can only show associations, and does not prove that avoiding meat directly reduces the odds of reaching 100,” Palinski-Wade added.
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The researchers suggested that including small amounts of animal-sourced foods could help older seniors maintain essential nutrients and avoid the muscle loss often seen in those who stick strictly to plants.
Eliminating all animal protein — particularly in a population that may already experience diminished hunger cues — can make it more difficult to meet adequate protein needs, potentially increasing the risk of nutrient deficiencies. (iStock)
Palinski-Wade offered some guidance for those looking to optimize nutrition later in life.
“For adults in their 80s and beyond, especially anyone losing weight or muscle, the priority should be maintaining a healthy weight and meeting protein and micronutrient needs — even if that means adding or increasing fish, eggs, dairy or well‑planned, fortified plant proteins and supplements.”
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Strict vegan or very low‑protein patterns at that age should be carefully monitored by a dietitian or clinician, with attention to B12, vitamin D, calcium and total protein, according to Palinski-Wade.
“Younger and healthier adults can still confidently use plant‑forward or vegetarian patterns to lower long‑term chronic disease risk,” she added.
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