Latest news with #LMNA
Medscape
a day ago
- Health
- Medscape
Testing for LMNA Mutations Called ‘Woefully Underutilized'
People with mutated copies of the LMNA gene are at high risk for cardiac laminopathies, including atrioventricular block and atrial or ventricular arrhythmias (VAs) leading to dilated cardiomyopathy. These autosomal dominant mutations have a high penetrance, meaning that a high percentage of persons with a pathogenic or likely pathogenic variant will develop health problems related to the gene. For those with cardiac manifestations, about 90% of carriers of LMNA mutations older than 30 years have a high risk for sudden death from arrhythmia — even patients with minimal left ventricular dilation and mild systolic impairment — well before the onset of heart failure. A long-term follow-up study from 122 consecutive carriers of LMNA mutations with cardiac conditions showed that most had experienced arrhythmia, heart block, embolic events, or heart failure within 7 years of diagnosis. Could some outcomes, such as sudden cardiac death, be averted with a more precise view of LMNA mutations? New research published in JAMA Cardiology shows pinpointing the type and location of the LMNA mutation may guide clinicians toward earlier treatment approaches to improve prognosis for these high-risk patients. These interventions might include earlier placement of implantable cardioverter-defibrillator (ICD) devices and family testing to detect the mutation before the onset of symptoms. 'Genetic testing for dilated cardiomyopathy is woefully underutilized,' said the paper's senior author, Neal Lakdawala, MD, an associate professor of medicine at Harvard Medical School and a cardiologist in the Heart and Vascular Center at Brigham and Women's Hospital, in Boston. In fact, claims data showed that fewer than 2% of patients with dilated cardiomyopathy undergo genetic testing. 'Prior research has established the prognostic power of a genetic diagnosis,' Lakdawala told Medscape Medical News . 'We took it one step further within a specific genetic etiology, to show that the type of gene variant and the location of a gene variant also matter.' The retrospective cohort study examined international registry data from 718 patients (mean age, 41.3 ± 14.3 years) with pathogenic or likely pathogenic variants of LMNA . The participants in the study had no prior history of malignant VA. The primary outcome was time to malignant VA, defined as sudden cardiac death, placement of an ICD, or other manifestations of hemodynamically unstable VA. The secondary outcome, advanced heart failure, was defined as nonsudden cardiac death, implantation of a left ventricular assist device, or heart transplant. Reflecting the high risk associated with LMNA mutations, Lakdawala said, nearly one third of the study participants experienced sudden cardiac death, hemodynamically unstable VA, or an ICD procedure during the 4.2-year follow-up period. In addition, 15% developed advanced heart failure, defined as the implantation of a left ventricular assist device, heart transplant, or nonsudden cardiac death. These outcomes occurred despite many patients having a baseline left ventricular ejection fraction (EF) in the normal range (mean EF was 56%, well above guideline-recommended thresholds of 35%-45% for ICD placement, the researchers reported). Looking deeper into the genes, Lakdawala and his colleagues found participants who had truncating LMNA variants — an abbreviated version of the protein — had worse arrhythmic outcomes, regardless of the position of this genetic mutation on the DNA sequence. On the other hand, those who exhibited missense variants of the LMNA gene — an altered amino acid on the DNA sequence — had a lower risk for harmful arrhythmias and better overall outcomes. Taken together, the location and nature of the gene variants could lead to specific predictions of cardiac risk, according to the researchers. A man with an EF of 50% and a truncating LMNA gene variant, for example, would have a 12% risk for VA within 5 years, but a 7.2% risk if a missense variant were present. For a woman with EF 50%, this risk would be 7.5% for a truncating variant vs 4.5% for a missense variant, if no other risk factors were present. Why Genetic Testing Is Key In an editorial accompanying the journal article, Sharlene M. Day, MD, a cardiomyopathy specialist and presidential professor at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, wrote 'the data from this study can also inform risk stratification even in healthy populations with incidental or secondary findings.' Integrating genetic findings into cardiomyopathy management should be 'a priority for all practicing cardiologists,' she wrote. 'The knowledge gap appears to be narrowing with respect to the importance of genetic testing in patients with cardiomyopathies,' Day told Medscape Medical News . 'But there's still opportunity to improve recommendations and referrals by cardiologists for genetic counseling and testing.' Testing typically consists of a broad panel identifying multiple gene variants, including LMNA , she said. If a gene variant is found in an individual patient, cascade testing of family members for that variant is often recommended. 'The current research study nicely highlights the impact of identifying not only the specific gene involved but the type of variation within that gene in terms of risk stratifying patients for adverse outcomes,' she said. Impact on Future Cardiology Guidelines Future clinical practice guidelines should emphasize the value of a genetic diagnosis for risk stratification in patients with dilated cardiomyopathy, especially for predicting sudden death and heart failure, Lakdawala said. The most recent guidelines on heart failure from the American College of Cardiology and the American Heart Association list a class 2A recommendation for placement of an ICD in patients with high-risk genes for dilated cardiomyopathy and an EF of 45% or lower, adding that primary preventive ICD may be considered for those with higher EF. The 2023 European Cardiomyopathy Guideline recommends placement of ICDs in patients with LMNA variants and an EF above 35% (class 2A if risk factors are present and class 2B if no risk factors are present). 'For updated guidelines, I think the most immediate impact would be to refine the LMNA risk score for ventricular arrhythmias to include the type and location of the LMNA variant,' Day told Medscape Medical News . 'Genetic testing has clinical ramifications that will help cardiologists take better care of their patients,' Lakdawala added. 'The take-home message is that they should order these tests!' Lakdawala reported receiving personal fees from Alexion, Bayer, Bristol Myers Squibb, Cytokinetics, Lexeo Therapeutics, Nuevocor, Pfizer, and Tenaya Therapeutics and grants from Bristol Myers Squibb and Pfizer. Day reported serving as chair of the steering committee for Lexicon Pharmaceuticals, on the data monitoring committee for Cytokinetics, and receiving grants from Bristol Myers Squibb.
BBC News
23-06-2025
- Entertainment
- BBC News
Youngest MBE winner takes on 'poo plod' for accessible toilets
The youngest person to receive an MBE has dressed as a toilet for a five-mile "poo plod" to raise money for accessible facilities at her Chillory-Watson, from Dorset, is walking and wheeling from her school in Branksome to Bournemouth Pier, and back, accompanied by her mother, Lucy, who is dressed as an inflatable emoji hopes to raise at least £9,000 for washing and drying facilities at the school, which will allow disabled students to go to the toilet 11-year-old, who has LMNA congenital muscular dystrophy - a progressive muscle-wasting condition, said it would enable them to "feel more independent". Carmela, originally from Wiltshire, was diagnosed with the condition in 2017, aged three, and has since taken on 25 fundraising and awareness campaigns, often dressed in superhero on her MBE in the King's Birthday honours, she said: "I can't find the words, honestly, I was thrilled."I love helping charities, I love fundraising for them and I will just do anything to help and give everyone hope for the future and for the charities."Carmela said she hoped her latest challenge would draw attention to a cause that meant a lot to her personally, and expressed the importance of remote controlled toilet facilities that allowed people with physical disabilities to use toilets on their own."Other people, and myself, like to be independent in the toilet," she said, adding it would "give them a sense of dignity".Teachers, pupils and parents from the school, all dressed in various toilet-themed outfits, set off on the walk with Carmela and her mother at 09:00 BST. You can follow BBC Dorset on Facebook, X (Twitter), or Instagram.
Miami Herald
18-06-2025
- Health
- Miami Herald
Telomir Pharmaceuticals Prevents Cellular Aging in Patient-Derived Cells from Children with Progeria - an Ultra-Rare Genetic Disorder that Causes Rapid Aging
Study used cell lines obtained from the Progeria Research Foundation to evaluate Telomir-1's effects on key drivers of accelerated aging MIAMI, FLORIDA / ACCESS Newswire / June 18, 2025 / Telomir Pharmaceuticals, Inc. (NASDAQ:TELO), a preclinical-stage biotechnology company focused on reversing biological aging and age-related diseases, today announced compelling new preclinical data showing that its lead candidate, Telomir-1, prevented cellular aging in human progeria cell lines obtained from the Progeria Research Foundation. Progeria, or Hutchinson-Gilford Progeria Syndrome (HGPS), is an ultra-rare pediatric disorder caused by a mutation in the LMNA gene. This mutation results in the production of an abnormal protein called progerin, which drives rapid biological aging in children. There are an estimated 400-500 known cases worldwide, including fewer than 30 children currently living with the disease in the United States. Symptoms typically begin within the first two years of life and include growth failure, joint stiffness, loss of body fat and hair, and severe cardiovascular disease. Children with progeria have an average life expectancy of just 13 to 15 years, with most dying from heart attacks or strokes at a young age. The only FDA-approved therapy for progeria, Zokinvy® (lonafarnib), is a farnesyltransferase inhibitor that has been shown to extend lifespan by an average of 4.3 years. However, Zokinvy does not reverse the underlying disease pathology or halt cardiovascular deterioration, which remains the leading cause of death. No approved therapy restores normal cell function or reverses the biological hallmarks of accelerated aging in progeria, highlighting a significant and urgent unmet medical need. Telomir-1 is designed to regulate intracellular metal ions, reduce oxidative stress, restore mitochondrial function, extend telomere length, reverse muscle loss, and reset age-associated DNA methylation patterns - all of which are critical biological pathways implicated in progeria and broader age-related diseases. In this study, conducted by Smart Assays, Telomir-1 was tested in cells taken directly from a child with HGPS. These cells were obtained from The Progeria Research Foundation ( The study evaluated cell viability, reactive oxygen species (ROS), and intracellular calcium signaling - a marker of mitochondrial dysfunction - under both normal and stress-induced conditions. Key findings include: Improved cell viability: Telomir-1 increased survival in a dose-dependent manner, both under basal conditions and even under stress conditions induced by copper and iron-two metal ions known to accelerate aging by generating oxidative damage and destabilizing DNA and of oxidative stress: Progeria cells exhibited abnormally high levels of reactive oxygen species (ROS), a hallmark of cellular aging. Telomir-1 normalized these levels, both under basal conditions and even when ROS was further elevated by toxic metal of mitochondrial function: Iron-induced calcium overload - a signal of mitochondrial damage and a known feature of HGPS - was significantly reduced with Telomir-1, indicating restored mitochondrial regulation and improved cellular energy balance. These results demonstrate that Telomir-1 directly addresses the core cellular dysfunctions driving disease features in progeria - not only protecting cells from damage but restoring critical biological functions. The fact that these results were observed in actual patient-derived human cells offers strong early validation of Telomir-1's therapeutic potential. "These results provide the strongest evidence to date that Telomir-1 is not only protective but also restorative at the molecular and cellular level," said Dr. Angel, Chief Scientific Advisor of Telomir. "What's especially promising is that the improvements we observed directly target the mechanisms known to drive disease progression in progeria - oxidative stress, metal toxicity, and mitochondrial instability. This level of functional rescue in actual patient-derived cells is highly encouraging as we move toward clinical translation. These studies come as further validation of the very promising results obtained previously in both nematode and zebrafish models of adult progeria." "These findings deepen our conviction that Telomir-1 can be a first-in-class therapeutic platform for rare aging syndromes and broader age-related diseases," said Erez Aminov, CEO of Telomir. "By demonstrating the ability to reverse cellular damage in human progeria cells, Telomir-1 represents a potential breakthrough for children who currently have no real options beyond modestly delaying the inevitable. This work also lays the foundation for broader applications in neurodegeneration, metabolic dysfunction, and systemic aging. The new data also build on previously reported studies in zebrafish and C. elegans nematodes harboring the wrn gene mutation (a model of adult progeria, or Werner syndrome), where Telomir-1 significantly extended lifespan, restored telomere length, reversed muscle degeneration, and normalized molecular age markers. Telomir is currently finalizing IND-enabling studies for Telomir-1 and plans to engage with the U.S. Food and Drug Administration (FDA) to explore regulatory pathways, including the potential for orphan drug designation. The company is evaluating multiple rare disease indications for initial clinical development. Cautionary Note Regarding Forward-Looking Statements This press release, statements of Telomir's management or advisors related thereto, and the statements contained in the news story linked in this release contain "forward-looking statements," which are statements other than historical facts made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These risks and uncertainties include, but are not limited to, the potential use of the data from our studies, our ability to develop and commercialize Telomir-1 for specific indications, and the safety of Telomir-1. Any forward-looking statements in this press release are based on Telomir's current expectations, estimates and projections only as of the date of this release. These and other risks concerning Telomir's programs and operations are described in additional detail in its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, which are on file with the SEC and available at Telomir explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact Information Helga Moya info@ 396-6723 SOURCE: Telomir Pharmaceuticals, Inc
