Drug duo synergy may help cystic fibrosis patients clear lung mucus, animal tests suggest

Two existing types of drugs synergize to improve the clearing of mucus from the lungs of animals with cystic fibrosis, a Stanford Medicine research team has found. The findings are published in the June 2026 issue of the Journal of Clinical Investigation. If replicated in humans, the discovery may provide a way to reduce chronic lung infections in people with cystic fibrosis.

Methacholine

Formoterol

"I really hope this discovery can help CF patients," said lead author Nam Soo Joo, Ph.D., a senior research scientist at Stanford Medicine. "If these drugs improve mucociliary clearance in people as much as they do in our animal models, we expect this to help remove pathogens from the lungs and reduce patients' airway infections."

The study's senior author is Carlos Milla, MD, a professor of pediatrics at Stanford Medicine and a pulmonologist who treats children with CF at Stanford Medicine Children's Health.

The research team showed that the drug combination—a beta adrenergic agonist, formoterol, and a low-dose cholinergic agonist, methacholine—was safe and well-tolerated in a small group of people, including individuals with CF and healthy volunteers. The drugs are already approved by the U.S. Food and Drug Administration for other uses, and the scientists are now planning a trial of the combination's effectiveness in CF patients.

The finding could be especially beneficial for the 10% to 20% of CF patients who do not respond to targeted medications for cystic fibrosis known as CFTR (cystic fibrosis transmembrane conductance regulator) modulators, Joo noted.

The synergistic medications may also help people with other respiratory conditions, such as chronic obstructive pulmonary disease or bronchiectasis, a chronic lung disease characterized by severe airway scarring, he added.

Cystic fibrosis is a relatively common genetic disease, affecting 1 in every 3,000 to 4,000 babies born in the United States. Patients have mutations in the cystic fibrosis transmembrane conductance regulator gene. In healthy people, the CFTR gene encodes protein channels that let chloride and bicarbonate ions cross cell membranes. But in CF patients, the channels malfunction, causing the lungs and digestive system to produce thick mucus. This sticky mucus harbors bacteria and makes CF patients vulnerable to chronic lung infections.

Drugs called CFTR modulators that restore the chloride channels' function have improved the lives of many CF patients by allowing their bodies to manufacture normal mucus. But up to 20% of patients' gene mutations are incompatible with CFTR modulator drugs, meaning the medications don't help.

That's why Joo's team was excited to find a different approach to the mucus problem.

A fortuitous finding

The researchers' discovery was an accident. They were studying whether various drugs could speed mucociliary clearance, in which the cilia, hairlike projections that line the passages into the lungs, beat in a coordinated way to move mucus and bits of foreign matter, such as bacteria or dust, out of the airways. The process keeps the lungs healthy.

During drug tests on tissue in a dish, the researchers used a combination of a beta adrenergic agonist and a cholinergic agonist to check that the tissues were viable. (Each of the two medication categories includes several drugs; at first, the researchers were not using drugs approved for use in people.) To the scientists' surprise, the drug combination—intended only as an experimental control—sped up mucociliary clearance.

Joo discussed this unexpected observation with study co-author Jeffrey Wine, Ph.D., an emeritus professor of psychology and of human biology.

"Jeff said, 'Do you think this may work in CF?'" Joo recalled. "I said, 'Well, probably not.'"

The combination seemed unpromising because people with CF are already known to have an abnormal response to beta adrenergic agonists. Meanwhile, cholinergic agonists administered alone cause people's airways to constrict in an asthma-like manner, which presents a safety concern.

A counterintuitive result

Even though they suspected the drug combination would fail, Joo's team tested it, first in airway tissue samples from a ferret model of CF, then in tissue and live animals including ferrets, rats, sheep, and pigs with pharmacologically induced or genetic CF.

In the new study, the researchers used formoterol and methacholine, which are a beta adrenergic agonist and a cholinergic agonist, respectively. The scientists chose these specific drugs because they are already approved by the FDA for use as inhaled medications.

Each drug caused a small increase in mucociliary clearance when given alone, but together their effects were far more pronounced. For instance, in rats with CF, the drug combination increased the animals' mucociliary clearance velocity to about 80% of that seen in healthy rats.

Follow-up experiments on tracheal tissue showed that the drugs given together increase fluid secretion, inhibit absorption of fluid, and raise the pH of the secreted fluid. These changes make the mucus less viscous and more mobile.

Furthermore, the researchers showed that when the drug combination was given to ferrets with CF that were also receiving a CFTR modulator drug, the animals could clear mucus more easily than when they received only the CFTR modulator, suggesting that the drug combination may benefit all CF patients.

In a small safety test in humans, as expected, methacholine caused airway constriction when given alone. But the two drugs in combination did not.

The results are exciting both for their implications for cystic fibrosis and for patients with other lung conditions, Joo said.

"Patients with other respiratory disorders like chronic obstructive pulmonary disease or bronchiectasis also have mucociliary clearance impairment, but compared with CF, it's mild," he said. "If we use this drug in other airway diseases, it may improve those patients as well, but we still require large-scale clinical trials to know the optimal combination and concentrations of these drugs."

https://en.wikipedia.org/wiki/Methacholine

https://en.wikipedia.org/wiki/Formoterol

Drug duo synergy may help cystic fibrosis patients clear lung mucus, animal tests suggest

Salt Substitutes Help Prevent High Blood Pressure

Replacing regular salt with a salt substitute can reduce high blood pressure in older adults, a new study has found.

Older adults who use a salt substitute are 40% less likely to develop high blood pressure compared to those who use regular salt, according to findings published Feb. 12 in the Journal of the American College of Cardiology.

“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said lead researcher Dr. Yangfeng Wu, executive director of the Peking University Clinical Research Institute in Beijing.

“It's crucial to recognize the impact of our dietary choices on heart health and increase the public’s awareness of lower-sodium options," he added in a journal news release.

High blood pressure is the leading risk factor for heart disease and heart-related death, according to the World Health Organization. It affects more than 1.4 billion adults worldwide and results in 10.8 million deaths each year.

For this study, researchers evaluated how sodium reduction might help the blood pressure of seniors residing in care facilities in China.

The study involved more than 600 participants, age 55 and older, from 48 care facilities. All patients had blood pressure under 104/90 mmHG, and were not on any blood pressure medications.

Half of the care facilities replaced salt with a salt substitute in residents’ meals, while the other half kept using regular salt, researchers said.

After two years, the incidence of high blood pressure was more than double at the facilities that kept using salt – 24.3 cases per 100 people-years versus 11.7 cases per 100 people-years at the facilities using salt substitute.

People-years take into account both the number of people in a study and the amount of time each person spends in the study.

What’s more, the salt substitutes did not cause dangerously low blood pressure, which also commonly affects older adults.

“Our results showcase an exciting breakthrough in maintaining blood pressure that offers a way for people to safeguard their health and minimize the potential for cardiovascular risks, all while being able to enjoy the perks of adding delicious flavor to their favorite meals,” Wu said.

In an accompanying editorial, nephrologist Dr. Rik Olde Engberink said the study offers an alternative to simply asking patients to cut back on salt intake – a strategy that has failed to gain wide support among the public.

In this trial, “the salt substitute was given to the kitchen staff, and the facilities were not allowed to provide externally sourced food more than once per week,” Olde Engberink, who practices at Amsterdam University Medical Center in The Netherlands, said in a news release.

“This approach potentially has a greater impact on blood pressure outcomes, and for this reason, salt substitutes should be adopted early in the food chain by the food industry so that the sodium-potassium ratio of processed foods will improve,” he added.

 https://www.jacc.org/doi/10.1016/j.jacc.2023.12.013

Salt Substitutes Help Prevent High Blood Pressure - Drugs.com MedNews

Drug Used to Treat Rheumatoid Arthritis May Also Help Prevent It

A clinical trial  showed that the  drug abatacept (Orencia) – which is already used to treat diagnosed rheumatoid arthritis – also can prevent people from progressing to the painful inflammatory disease.

Abatacept eases symptoms and prevents joint damage in rheumatoid arthritis patients by dampening the immune system, researchers said.

About 1.3 million Americans live with rheumatoid arthritis, which occurs when the body’s immune system starts attacking tissues in the joints, causing inflammation, pain and swelling.

Day’s clinical trial showed that abatacept also is effective in preventing the onset of rheumatoid arthritis.

About 6% of patients treated with abatacept developed arthritis compared to 29% given a placebo following a year of treatment, according to clinical trial results published Feb. 13 in The Lancet.

“This is the largest rheumatoid arthritis prevention trial to date and the first to show that a therapy licensed for use in treating established rheumatoid arthritis is also effective in preventing the onset of disease in people at risk,” researcher Andrew Cope, head of the King’s College London Center for Rheumatic Diseases, said in a news release.

“These initial results could be good news for people at risk of arthritis, as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue,” he continued.

For the clinical trial, researchers recruited 213 patients older than 18 at high risk of rheumatoid arthritis. They all had early symptoms like joint pain, but no swelling that would lead to a formal diagnosis.

Rheumatoid arthritis most often begins in middle age, but also can affect much younger adults, researchers said.

“Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time,” Day said.

Half of the participants were treated with abatacept and the other half with a placebo every week for a year. The drug is given by weekly injections at home or in a hospital via an IV drip.

After a year of treatment, the drug was stopped and patients were monitored to see how many would develop rheumatoid arthritis.

After the full two years, 25% of abatacept patients had progressed to rheumatoid arthritis compared with 37% of those on a placebo.

“The results clearly show that during the treatment period almost all individuals receiving the biologic drug showed no symptoms or signs of RA compared with the control population,” Ravinder Maini, an emeritus professor of rheumatology at Imperial College London who was not involved in the research, said of the clinical trial.

Drug Used to Treat Rheumatoid Arthritis May Also Help Prevent It 

Botanical drug is shown to help patients with head and neck cancers

In continuation of my update on Curcumin

In a UCLA-led phase I clinical trial, a new plant-based drug called APG-157 showed signs of helping patients fight oral and oropharyngeal cancers. These cancers are located in the head and the neck.

APG-157  (a botanical drug containing multiple polyphenols, including curcumin see above structure), is made up of multiple compounds produced by plants, including curcumin. UCLA Jonsson Comprehensive Cancer Center researchers found that treatment with this botanical drug resulted in high concentrations of curcumin and its byproducts circulating in the blood and absorbed by tumor tissues within three hours after being taken orally.

APG-157 reduced the concentration of cytokines—proteins involved in inflammation—in the saliva when administered to cancer patients. The therapy also reduced the relative abundance of Bacteroides species, a group of gram-negative bacteria. Gram negative refers to a group of dangerous bacteria that have an outer layer which hides them from the immune system. The relative abundance of gram-negative bacteria compared to the presence of other types of bacteria is correlated with oral cancer.

APG-157 also resulted in the expression of genes that are associated with attracting immune system T cells to the tumor area. This therapy could have a beneficial effect when used in combination with immunotherapy drugs that help immune system T cells recognize and kill tumors.

The treatment did not have any adverse effects on the study's participants.

Cancers of the head and neck account for 4% of all cancers. About 650,000 new cases are reported each year around the world. People with advanced head and neck cancers have a low survival rate and current treatment options such as surgery, radiation and chemotherapy can have adverse effects. Therefore, more effective and less toxic therapies are needed to help improve the quality of life and outcome for those with these cancers.

APG-157 is a botanical drug developed under the FDA's Botanical Drug Guidance, which includes requirements for production of plant-based therapies that are marketed as prescription medications. The drug is made up of botanical compounds including curcumin from the Curcuma longa plant, which is commonly referred to as turmeric and is a member of the ginger family.

Curcumin is one of the medicinally active or therapeutic molecules that has been tested as a possible treatment to help fight multiple cancers because it is an antioxidant that reduces swelling and inflammation. However, there is poor absorption into the bloodstream when curcumin is taken orally. In this study, UCLA researchers found that when APG-157 is taken through oral mucosal absorption, patients have high levels of curcumin circulating in their blood and absorbed by cancer tissues.

UCLA researchers conducted the study of APG-157 comparing 12 people who had oral and oropharyngeal cancer with a control group of 13 people who did not have cancer. The reason both the people with cancer and without cancer were part of the study was to show that the drug was not toxic to either people with cancer or those without cancer.

The medication was given each hour for three hours and was delivered as a lozenge that slowly dissolved in the mouth. Blood and saliva samples were collected beforehand—each of the three hours the medication was administered—and 24 hours after the last dosage. The medication was given to 12 people (some who had cancer and some who did not) and a placebo was given to 13 people. Blood and electrocardiogram tests did not show increased toxicity in the people who took the active medication in comparison with the people who took the placebo, regardless of whether they had cancer or not.

For the cancer patients who took the medication, there was a decrease in Bacteroides and an increase in T cells in the tumor tissue as compared to cancer patients who took the placebo. Neither the subjects nor the investigators knew whether the drug or a placebo was given when reviewing the blood and saliva test results of the blinded study.

APG-157 is a botanical drug that has low toxicity. It works effectively to reduce inflammation that contributes to the growth of cancer cells. It also attracts T cells to the tumor micro-environment. When used in combination with immunotherapy drugs, APG-157 might have the ability to make the immune system more effective in attacking head and neck cancers. With potential to inhibit the growth of Bacteroides species, APG-157 could also improve cancer therapy through oral microbial changes.

https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32644

Could Diabetes Drug Metformin Help Keep People Slim?

New research suggests a first-line drug for treating type 2 diabetes   'metformin'  may help people with pre-diabetes maintain long-term weight loss.

People who lost weight while taking metformin maintained a loss of about 6% of their body weight for six to 15 years. People who lost weight through lifestyle changes -- eating healthily and exercising regularly -- managed to keep off just under 4% of their initial body weight for the same period, the study found.

Metformin doesn't seem to be particularly helpful for shedding pounds in the first place, though. In fact, an earlier phase of the study found that people were much more likely to lose 5% or more of their body weight through lifestyle changes -- healthy eating and exercising -- than by using metformin.

"Although lifestyle changes were superior for inducing weight loss early on, metformin was better for long-term weight maintenance," said senior study author Dr. Kishore Gadde. He's a professor in heart disease prevention at the Pennington Biomedical Research Center in Baton Rouge, La.

Not everyone is convinced that metformin can keep you slim, however. After reviewing the findings, Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York City, said, "This study was very well done, but it doesn't show metformin is effective for everyone. The ones on metformin who did lose weight only regained a little less weight."

He added that metformin isn't well-tolerated by a lot of people. It can cause digestive problems, such as nausea and diarrhoea.

An  effective intervention for losing weight and maintaining that loss is clearly needed. Nearly three-quarters of the American population is overweight or obese -- a major risk factor for type 2 diabetes, according to the U.S. Centers for Disease Control and Prevention.

Losing a significant amount of weight more than 5% of your body weight  seems to help prevent pre-diabetes from turning into type 2 diabetes, and can help delay the progression of type 2 diabetes.

The latest study was a continuation of the three-year diabetes prevention clinical trial that compared three different groups of people with pre-diabetes to see what type of intervention would help prevent type 2 diabetes from developing. One group was given metformin, another was coached on intensive lifestyle changes, and the third group was given a placebo.

This study found that lifestyle changes led to the greatest initial weight loss, followed by the metformin group, according to Gadde.

From the original study group -- more than 3,000 people -- just over 1,000 lost more than 5% of their body weight.

The researchers followed this group for as long as 15 years to see who maintained their weight loss.

People taking metformin had the greatest weight loss from years six to 15, according to the study. The study also found that being older and losing a greater amount of weight in the first year were consistent predictors of lasting weight loss, the study authors said.

Gadde said it's not exactly clear why the metformin group was better at maintaining weight loss. "Metformin does reduce food intake a little bit, but it's not a dramatic effect. And, from what we know, it doesn't significantly alter energy expenditure."

He said other recent research suggests that metformin may alter the body's microbiome (the healthy bacteria in your gut). It also seems that metformin may have some effects on muscle function. But Gadde said, more research is necessary to know for sure.

Could Diabetes Drug Metformin Help Keep People Slim?

Statins Help the Heart, No Matter What Your Age

Cholesterol-lowering statins are already known to help cut heart risks for seniors and the middle-aged. Now, research confirms the meds can also help people aged 75 and older.

"Statin therapy has been shown to prevent cardiovascular disease in a wide range of people, but there has been uncertainty about its efficacy and safety among older people," said lead investigator Anthony Keech. He's a professor of medicine, cardiology and epidemiology at the University of Sydney in Australia.

He and colleagues at the University of Oxford in England analyzed the findings of 28 large clinical trials of statins. The trials involved nearly 187,000 people in six age groups: younger than 55; 55 to 60; 60 to 65; 65 to 70; 70 to 75; and older than 75.

"Our study summarized all the available evidence from major trials to help clarify this issue. We found that there were significant reductions in major vascular events in each of the six age groups considered, including patients [who were] aged over 75 at the start of treatment," Keech said in an Oxford news release.

Major vascular events included heart attack, stroke and procedures to clear clogged arteries.

"Statin therapy appears to be just as effective in people aged over 75 years as it is in younger people," study co-investigator Jordan Fulcher said in the news release. Fulcher is a cardiovascular research fellow at the University of Sydney.

"We have definitive evidence that statins benefit older people who have suffered a heart attack or stroke. Fewer healthy older people were represented in these trials, so more information in this group of people would help confirm the same benefits that we see in our overall trials population," he said.

Fulcher noted that a new randomized trial in Australia is exploring whether statins prolong disability-free survival in a healthy population.

The risk of heart attacks and strokes rises sharply with age, yet statins are not used as widely in older people as they should be, study co-investigator Colin Baigent said in the news release. He's director of Oxford's Medical Research Council Population Health Research Unit.

"Since the risk of heart attack and stroke increases with age, the potential benefits are likely to be even greater for older people," he said.

"Therefore, there is a need to ensure that patients at risk of cardiovascular disease due to their age are offered statin therapy where there is good reason to believe that it will be beneficial," Baigent said.

Anyone with concerns about whether statin therapy is right for them should discuss it with their health care provider, he added.