Latest news with #LDL
Business Wire
12 hours ago
- Health
- Business Wire
PRD Therapeutics Announces Initiation of First-in-Human Study for PRD001
TOKYO--(BUSINESS WIRE)--PRD Therapeutics, Inc., a clinical stage company focused on the development of novel lipid metabolism regulators targeting homozygous familial hypercholesterolemia (HoFH) and metabolic dysfunction associated fatty liver disease (MASH/MASLD), today announced that the company recently initiated dosing in a First-in-Human (FIH) clinical trial of PRD001, a first-in-class SOAT2 (formerly known as ACAT2) selective inhibitor. 'We are excited to initiate dosing in this clinical trial of PRD001. Many clinical trials have been conducted on SOAT1/2 dual or SOAT1 selective inhibitors, but this is the first clinical trial of an SOAT2 selective inhibitor' said Kanji Hosoda, Ph.D., CEO and co-founder of PRD Therapeutics. 'Several results with SOAT1 or 2 knockout mice have been published, suggesting that knocking out or inhibiting only SOAT2 is crucial to demonstrate safety and efficacy. PRD001 is the world's first and only SOAT2-selective inhibitor and is expected to exhibit safety and efficacy in humans as well. Our preclinical animal models (LDL-R KO mice; HoFH model, and high-fat diets induced MASH model mice) have shown that PRD001 lowers blood and liver lipids and suppresses the progression of fatty liver and atherosclerosis with no adverse events. PRD001 has the potential to be the first-in-class effective and safe oral therapy for HoFH patients suffering from no or extremely low LDL receptor activity.' This FIH Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics, and the signs of early efficacy (LDL-C lowing effect, and liver fat quantitative value using MRI-PDFF) of PRD001 in adult healthy volunteers. More information can be found at NCT07034183. About PRD001 PRD001 is a first-in-class, orally available small molecule SOAT2-selective inhibitor. It uniquely controls three key pathways of lipid metabolism; cholesterol synthesis in the liver, cholesterol absorption in the small intestine, and uptake of blood LDL-C with a single drug, leading to a potent reduction in a blood LDL-C level independent of the LDL receptor. This research and development is supported by Japan Agency for Medical Research and Development (AMED) under Strengthening Program for Pharmaceutical Startup Ecosystem (Project title: " Development of First-in-class oral lipid metabolism regulator PRD001 and POC obtained for lipid metabolism disorder ").
India Today
20-06-2025
- Health
- India Today
It's not what you eat, but how: The cooking mistakes raising India's cholesterol
India is a land of turmeric, garlic, whole grains, and lentils -- ingredients celebrated globally for their health benefits, especially heart paradoxically, the country also faces a growing burden of lifestyle diseases, including high cholesterol, even among those who don't eat processed junk what's going wrong? Doctors say the problem lies not in what we eat, but how we prepare and consume a paradox based more on the way we prepare and what we mix, not the ingredients,' says Dr. Vivudh Pratap Singh, Senior Consultant, Interventional Cardiology at Fortis Escorts Heart Institute, New Delhi, adding that Indian kitchens are rich in heart-healthy ingredients, but the issue is generally with "overcooking, excessive ghee, refined carbs, deep-frying, and poor portion control.'HEALTHY FOODS, UNHEALTHY HABITSAccording to Vandana Verma, Head of Dietetics at Sir Gangaram Hospital, India's food culture is nutritionally rich with millets, lentils, spices, and vegetables forming the base of many meals. But that potential is often lost due to cooking practices that damage their nutritional profile. Doctors say the problem lies not in what we eat, but how we prepare and consume it. () advertisement'Even nutrient-rich ingredients lose their benefits when paired with harmful cooking and eating practices. Deep frying, reusing oils, and using full-fat dairy and refined carbohydrates turn wholesome foods into cholesterol-raising meals," she highlights several problematic habits:Reused oils that form trans fatsExcessive frying of snacks and meatsPortion overload with carbs and fatsHidden sugars in chutneys, sauces, and sweetsSaturated fat overload from malai, ghee, and vanaspatiThese habits, combined with inactivity and late-night eating, create a perfect storm for rising cholesterol AND THE HIDDEN MARKERSCholesterol isn't inherently bad. It's a waxy substance that helps build cells and travels through the bloodstream as LDL (Low-Density Lipoprotein) and HDL (High-Density Lipoprotein).LDL is the "bad" kind that deposits cholesterol in artery is the "good" kind that removes cholesterol from the bloodstream. Cholesterol isn't inherently bad. It's a waxy substance that helps build cellsand hormones. () 'LDL puts cholesterol down, detrimental to the heart. HDL gets rid of it, beneficial to the heart,' Dr. Singh explains. 'Maintaining LDL levels low and HDL levels high is key.'advertisementBut doctors are now looking beyond just LDL and HDL. Dr. Singh points out four other important markers that reveal a more complete picture of cardiovascular risk:Non-HDL cholesterolApolipoprotein B (ApoB)Lipoprotein(a) or Lp(a), especially in those with a family history of early heart diseaseSmall, dense LDL particles, which are more likely to penetrate artery walls'These hidden markers often explain why some people with 'normal' LDL still face cardiovascular issues,' he CURES ARE REAL, IF YOU USE THEM RIGHTExperts agree that the Indian kitchen is still one of the best places to begin managing cholesterol, provided it's approached the right Singh recommends a daily mix of oats, fruits, five servings of vegetables, 30g of mixed nuts and green tea.'Together, this combination can naturally reduce LDL by up to 20–25%,' he Verma echoes this view, listing natural cholesterol-lowering foods:advertisementSoluble fibre from oats, apples, and flaxseedsPlant sterols from nuts and seedsOmega-3 fatty acids from walnuts, flaxseeds, and oily fishGarlic and green tea, known for their heart-supporting compoundsWhole grains and soy products, which support lipid control Experts agree that the Indian kitchen is still one of the best places to begin managing cholesterol, provided it's approached the right way. () She adds, 'Our heritage holds the answer. The goal is not to eliminate fat but to make smarter choices, grill instead of deep fry, control portions, use less oil, and avoid refined sugars and carbs.'Ultimately, managing cholesterol is not about trendy superfoods or extreme about rediscovering and respecting the logic behind traditional ingredients and cooking methods.'Our diet has the potential to safeguard the heart. The solution lies in reframing how we cook and consume, not what we prepare,' Dr. Singh concludes.
Irish Examiner
07-06-2025
- Politics
- Irish Examiner
Full committee of Limerick football league 'stood down' by FAI
The FAI have suspended the entire Limerick District League committee while they launch an independent investigation into governance concerns. In an unprecedented move, the association said it would be inappropriate for the league to proceed with their upcoming AGM. It says that they and the Munster FA 'will be able to support the delivery of football under the jurisdiction of the LDL while the investigation takes place.' Governance in Limerick amateur football has been a talking point in recent years. Following contact by a cohort of LDL clubs, the FAI issued a list of 11 recommendations in 2021, including the introduction of term limits, rule book overhaul and the auditing of 2020's financial accounts. It is understood that the FAI's recent involvement stemmed from a complaint lodged protected by confidentiality. Multiple issues were raised when an FAI delegation met with the LDL in December but a standoff ensued until this latest nuclear development materialised on Thursday. 'The concerns raised vary in their nature,' wrote FAI President Paul Cooke in correspondence to the committee. 'Some relate to the processes, policies and practices of the League - both from the perspective of constitutional/administrative matters and also around the delivery of football - whilst others relate to the culture within the League and allegations of derogatory behaviour and inappropriate conduct from people involved at Committee level.' Reference was made to the state agency responsible for exchequer funding. 'Sport Ireland is aware of the concerns that have been raised and expects them to be addressed appropriately.' The letter added: 'Whilst this investigation is being established, we request that all League committee members step away from their committee duties with immediate effect (and this includes any other position that a committee member may hold under the jurisdiction of the FAI). Committee members, many of whom double their duties with the Limerick Schoolchildren's League which won the girls Gaynor Cup at University Limerick on Friday, have until Monday morning to provide written agreement with this directive.
Medscape
28-05-2025
- Business
- Medscape
No, KETO-CTA Study Did Not Upend Causal Evidence on ASCVD
Few argue that eating too many carbohydrates is a key cause of the obesity crisis. The ideal solution would be to moderate carbohydrate intake to the amounts consumed by Sicilians. But some people have gone to the extreme of eliminating nearly all carbs. One result of eating only fat and protein is ketosis. Another may be a rise in atherogenic lipid particles, such as low-density lipoprotein cholesterol (LDL-C). Lean-Mass Hyperresponders Authors of the observational KETO-CTA study purport to show that a subgroup of people on keto diets who sustain serious increases in lipids may be protected from progression of atherosclerosis. This, despite nearly a half-century of evidence that higher LDL-C levels lead to coronary artery disease. They deemed this subgroup lean-mass hyperresponders(LMHRs). The idea stems from the observation that there may be heterogeneity in the LDL-C response to a keto diet. A meta-analysis (by some of the KETO-CTA authors) included 41 trials involving low-carbohydrate diets and found that rises in LDL-C turned largely on baseline BMI. Specifically, for trials including patients with a mean baseline BMI < 25, LDL-C increased by 41 mg/dL; for trials with a mean BMI of 25-35, LDL-C did not change; and for trials with a mean BMI ≥ 35, LDL-C decreased by 7 mg/dL. The association of baseline BMI with LDL-C was much stronger than the effect of dietary saturated fat. In the LMHR group, the rise in LDL-C can be striking, sometimes well north of 300 mg/dL. The obvious question is whether (or how much) this raises atherosclerotic risk. The best way to study this question would be long-term trials where people are randomly assigned and are adherent to specific diets. It would take years to sort out the effects because atherosclerosis is slowly progressive. Another way, perhaps the only realistic way, is to use surrogate markers of atherosclerosis, which now include imaging of the vessel itself. The KETO-CTA Study The KETO-CTA study, published in JACC: Advances , garnered lots of attention on social media. First, I will tell you the topline findings and then the critical appraisal. The authors aimed to study the association between plaque progression and its predicting factors in participants with an LMHR pattern. Plaque progression was measured on coronary CT imaging performed at baseline and repeated at 1 year. Images were blindly read, and software was required to quantify plaque characteristics. The authors recruited 100 individuals with the LMHR phenotype who had been on a ketogenic diet for at least 2 years to participate in the single-arm observational study. To qualify, they had to have a low BMI and a keto-induced LDL-C ≥ 190 mg/dL, HDL-C ≥ 60 mg/dL, triglycerides ≤ 80 mg/dL, and evidence of being metabolically healthy (normal CRP and A1c). The keto-induced criteria required that individuals had an LDL-C < 160 mg/dL before adopting the diet. They don't say how many individuals they screened to find these participants. Those included in the study had striking numbers. Despite an average BMI of 22, they had mean LDL-C levels of 254 mg/dL, HDL-C of 89 mg/dL, and triglycerides of 67 mg/dL. The average age was 55 years and most were men. They could not be on lipid-lowering therapy, which is remarkable for patients with very high LDL-C. Adherence to the keto diet was high and confirmed by beta-hydroxy-butyrate levels. Results Over the year, there were no substantial changes in ApoB or BMI, which you would expect because participants were on a stable keto diet. The presentation of the results was peculiar. The authors preregistered the study and declared the primary endpoint as the change in noncalcified plaque volume. But they did not formally present this endpoint. Instead, they gave the median change in percent atheroma volume, which was 0.8%. The primary endpoint was presented in a figure in which a horizontal line represented each individual. No quantification was given, but visual inspection of the graph revealed that most individuals sustained an increase in noncalcified plaque volume. The lack of clear presentation of the primary endpoint caused a stir online. This led the first author to present it in on X. The numerical pooled change in noncalcified plaque burden was an increase of 18.8 mm3. In the manuscript, they emphasized the correlations and lack of correlations. Neither the change in ApoB throughout the study nor the ApoB at the beginning of the study was associated with the change in noncalcified plaque volume. There was also no correlation between LDL-C and change in noncalcified plaque volume. The main finding was that the baseline coronary artery calcium score was positively associated with change in noncalcified plaque volume as was baseline plaque. They list four differences between the LMHR subgroup and people with elevated lipids from other metabolic risk factors: Difference 1: Their LDL-C and ApoB elevations are dynamic and result only from the metabolic response to carb restriction. Their LDL-C and ApoB elevations are dynamic and result only from the metabolic response to carb restriction. Difference 2: They are normal weight and metabolically healthy (ie, they don't have obesity, diabetes or insulin resistance). They are normal weight and metabolically healthy (ie, they don't have obesity, diabetes or insulin resistance). Difference 3: Their high LDL-C and ApoB are part of a lipid triad that includes high HDL-C and low triglycerides, representing a metabolic signature of a distinct physiologic state. Their high LDL-C and ApoB are part of a lipid triad that includes high HDL-C and low triglycerides, representing a metabolic signature of a distinct physiologic state. Difference 4: The degree of this phenotype appears inversely related to BMI ('leanness'), consistent with the idea that it is a metabolic response to carbohydrate restriction that is accentuated in leaner, more metabolically healthy persons. The authors go on to make highly provocative conclusions, such as: Conclusion 1: The LMHR population constitutes a unique and important natural experiment evaluating the lipid heart hypothesis in an unprecedented manner. The LMHR population constitutes a unique and important natural experiment evaluating the lipid heart hypothesis in an unprecedented manner. Conclusion 2: The data are consistent with the notion that elevated ApoB, even at extreme levels, does not drive atherosclerosis in a dose-dependent manner in this population of metabolically healthy individuals. The data are consistent with the notion that elevated ApoB, even at extreme levels, does not drive atherosclerosis in a dose-dependent manner in this population of metabolically healthy individuals. Conclusion 3: These insights can facilitate personalized treatment and risk-mitigation strategies based on modern, cost-effective cardiac imaging. For instance, LMHRs with CAC = 0 at baseline (n = 57) constitute a low-risk group for plaque progression, despite high LDL-C. These insights can facilitate personalized treatment and risk-mitigation strategies based on modern, cost-effective cardiac imaging. For instance, LMHRs with CAC = 0 at baseline (n = 57) constitute a low-risk group for plaque progression, despite high LDL-C. Conclusion 4: Because of the strong correlation of baseline coronary calcium with progression of noncalcified plaque, they coin the phrase plaque begets plaque. 6 Reasons the Keto-CTA Conclusions Are Problematic You don't have to be an expert in lipids, atherosclerosis, or imaging to oppose these conclusions. The study has limitations, but the main problem is the authors' outsized claims. I will outline six reasons why their conclusions are problematic: First, the primary endpoint of change in noncalcified plaque volume went up. The increase of 18.8 mm3 was 2.5 times higher than they predicted in their study protocol. If you believe that this endpoint is a great surrogate, the results are ominous. Second, imaging tests are almost always terrible surrogates. To assess risk, you need to measure cardiovascular events. Small, uncontrolled studies are fine, but you cannot claim clinical importance just because you weaved a nice story about high LDL-C in LMHRs being different from high LDL-C in other patients. Third, we have about 70 years of data supporting LDL-C being causal for atherosclerosis. Nearly every Bradford Hill criterion for causation is met for LDL-C and atherosclerosis. To claim an exception, you need more rigorous evidence than KETO-CTA. Fourth, assuming you believe the plaque images are precise, reproducible, and clinically relevant, KETO-CTA suffers from a lack of control. All they had to do is recruit a group of people eating another type of diet (eg Mediterranean diet) and make a comparison. Fifth, the authors don't tell us how many people they screened to find these 100 LMHRs. I get the sense they are a highly selected bunch. Sixth, the question of heart health from a specific diet will be difficult to sort out. Nutritional studies always are. A randomized trial in a prison might work, but cardiac event rates in young people, even with keto-induced-high LDL-C, will be infrequent. What's more, the LMHR group surely do other things that affect heart disease, like exercise, not smoking, etc. One final comment on the authors' messaging. It's been egregious and antiscientific. Their rhetoric and spin outdo some of the most hyped late-breaking trials. This was a small, noncontrolled observational study wherein the primary endpoint went the wrong way. It's nowhere near close to upending decades of causal evidence on the role of LDL-C and atherosclerosis. The journal editors and peer reviewers failed to modulate the outsized conclusions. I don't know what the solution is for this type of behavior, but I oppose it in the strongest terms.
NBC News
07-05-2025
- Health
- NBC News
New cholesterol drug lowers LDL when statins aren't enough, study finds
A new medication that combines an already approved drug with a new unapproved one has been shown to cut the level of LDL, or 'bad' cholestero l, when statins aren't helping enough. In the Phase 3 trial, Cleveland Clinic researchers found that the combination of the new drug, obicetrapib, with an established medication, ezetimibe, reduced low-density lipoprotein (LDL) cholesterol levels by 48.6% after about three months' use — producing more effective results than either drug alone. Ezetimibe is a cholesterol-lowering drug that is often prescribed with statins to reduce LDL even more. The research was presented Wednesday during a late-breaking science session at the annual meeting of the European Atherosclerosis Society in Glasgow, Scotland, and simultaneously published in The Lancet. In the multicenter clinical trial, the lead researcher, Dr. Ashish Sarraju, a preventive cardiologist at the Cleveland Clinic, and his colleagues enrolled 407 patients with a median age of 68 with LDL cholesterol levels greater than 70 mg/dL even though they had taken medication to lower it. The participants were randomly assigned to four groups: a group for a pill that combined obicetrapib with ezetimibe, a group for each of the drugs separately and a placebo group. All participants continued on the medications they were taking before they started the trial, along with the medications being studied. The reason: Some people have to take a number of prescriptions to get LDL down to desired levels. 'We need to give patients and their doctors all the options we can to try to get LDL under control if they are at risk for, or already have, cardiovascular disease,' Sarraju said. 'In higher-risk patients, you want to get LDL down as quickly as possible and keep it there as long as possible.' High-risk patients either had had strokes or heart attacks or were likely to in the future. For that reason, the researchers enrolled patients in the trial who, despite already being on statins or even high-intensity statins, still had LDL levels that were too high. The hope is that lowering LDL levels will reduce the risk of adverse cardiovascular events such as strokes and heart attacks. According to the American Heart Association, the optimal total cholesterol level for an adult is about 150 mg/dL, with LDL levels at or below 100 mg/dL ('dL' is short for 'deciliter,' or a tenth of a liter). For high-risk patients, Sarraju recommends an LDL no higher than 70 mg/dL. The trial was funded by the maker of obcetrapib, Netherlands-based NewAmsterdam Pharma. It expects to have conversations with the Food and Drug Administration about approval for the new combo drug 'over the course of the year,' a spokesperson said. A multitude of modifiable factors can result in high LDL, such as a diet high in saturated fats, processed foods and fried foods; being overweight; smoking; and older age. Dr. Robert Rosenson, director of lipids and metabolism for the Mount Sinai Health System in New York City, said other drugs in the same class have failed to reduce heart attacks or stroke, 'but I am cautiously hopeful.' The drugmaker is currently running an additional trial to determine if the combo drug not only lowers cholesterol but also protects against adverse heart events. While lifestyle changes can help bring down LDL, levels remain stubbornly high for some people. Only 20% of patients at high risk of heart disease are able to manage their LDL, said Dr. Corey Bradley, a cardiologist at the Columbia University Vagelos College of Physicians and Surgeons. Heart disease is the leading cause of death for adults in the United States. 'High LDL is one of the leading risk factors for heart disease, and we have such a poor handle on controlling that risk,' Bradley said. 'Many people have such a high LDL they will require multiple agents to control it.'
