Mitochondrial complex I (NADH dehydrogenase)

TOKYO--( BUSINESS WIRE )--LUCA Science Inc., in collaboration with Osaka University and Washington University School of Medicine in St. Louis, announces the publication of a transformative study in Nature Metabolism demonstrating the potential of mitochondria transfer-based therapies to alleviate symptoms and reduce the morbidity and mortality in a Leigh Syndrome (LS) mouse model. LS is a severe and often fatal inherited mitochondrial disease for which no effective therapies currently exist. The study, titled "Mitochondria Transfer-Based Therapies Reduce the Morbidity and Mortality of Leigh Syndrome," was conducted by an international team of researchers led by principal investigator Dr. Jonathan Brestoff. The research offers compelling evidence that transplantation of healthy wild-type (WT) mitochondria can ameliorate the symptoms and extend the lifespan of Ndufs4–/– mice, a well-established model for studying mitochondrial disease in Leigh Syndrome. Leigh Syndrome is a devastating neurodegenerative mitochondrial disease caused by mutations in genes essential for mitochondrial metabolism, leading to severe metabolic dysfunction. It typically presents in infancy or early childhood with severe symptoms such as muscle weakness, developmental delays, breathing difficulties, and seizures, often leading to a shortened lifespan. This study breaks new ground by showing that wild-type bone marrow transplantation, or administration of isolated mitochondria, can restore mitochondrial function in multiple organs, improve neurological outcomes, enhance energy expenditure, and extend lifespan in LS-affected mice. “Patients with LS and their families are in need of new therapies, and I hope that our studies open the possibility of using mitochondria transplantation to treat LS and other mitochondrial diseases,” said Dr. Jonathan Brestoff, senior author and Assistant Professor of Pathology and Immunology at WashU School of Medicine in St. Louis. “We are excited to present these findings, which demonstrated a convincing preclinical proof-of-concept in the therapeutic potential of mitochondria transfer in treating inherited mitochondrial diseases,” said Dr. Rick C. Tsai, one of the co-authors and CEO at LUCA Science. “We have established a manufacturing process that enables the production of off-the-shelf MRC-Q, and we are ready to initiate GMP development activities to advance MRC-Q towards clinical development. The study’s key findings include: - Wildtype Bone Marrow Transplantation: WT bone marrow transplantation led to significant improvements in the morbidity and mortality of Ndufs4–/– mice, correlating with the release of extracellular mitochondria and transfer of healthy mitochondria to diseased cells across multiple organs. - Autologous Mitochondria Transfer: Administration of isolated WT mitochondria extended lifespan, improved neurological function, and enhanced energy expenditure in LS-affected mice. - Cross-Species Mitochondria Transfer: Remarkably, storable human M itochondria o R ganelle C omplex Q (MRC-Q) by LUCA Science Inc. administered to Ndufs4–/– mice also ameliorated the symptoms of LS, suggesting the broader applicability of MRC-Q as biopharmaceutical therapies. This publication marks a significant milestone in the field of mitochondrial medicine and underscores the potential of mitochondria transfer as a therapeutic strategy for treating complex mitochondrial disorders. LUCA Science remains committed to advancing this research with the ultimate goal of developing effective treatments for patients suffering from mitochondrial diseases. The full paper is available in the latest issue of Nature Metabolism TITLE: Mitochondria transfer-based therapies reduce the morbidity and mortality of Leigh syndrome DOI: 10.1038/s42255-024-01125-5 LINK: https://www.nature.com/articles/s42255-024-01125-5 About LUCA Science Inc. LUCA Science is a pioneering biotechnology company focused on developing innovative therapies based on mitochondrial biology. The company’s mission is to harness the power of mitochondria to treat a wide range of diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic conditions. With cutting-edge research and a commitment to improving patient outcomes, LUCA Science is leading the way in mitochondrial medicine.

The human body has sophisticated defenses against the deposition of calcium minerals that stiffen heart tissues, researchers at the University of Illinois Urbana-Champaign and collaborators at UCLA Health and the University of Texas at Austin found in a new study that provides the first detailed, step-by-step documentation of how calcification progresses. The human body has sophisticated defenses against the deposition of calcium minerals that stiffen heart tissues, researchers at the University of Illinois Urbana-Champaign and collaborators at UCLA Health and the University of Texas at Austin found in a new study that provides the first detailed, step-by-step documentation of how calcification progresses. "Heart disease is the leading killer annually -- about 18 million deaths per year -- and that number is growing. A large proportion is the result of calcification," said study leader Bruce Fouke, a U. of I. professor of earth science and environmental change and director of the Roy J. Carver Biotechnology Center at Illinois. "When the aortic valve calcifies, an ultra-invasive surgery to replace the valve is the only option currently. That heightens the urgency to get a handle on this process to more effectively move forward with drug development and testing." The aortic valve is the portal through which oxygenated blood gets pumped out of the heart to the body, opening and closing more than 3 billion times during the average lifespan. Calcium deposits can grow within the three tissue flaps that make up the valve, called leaflets, stiffening them and leaving them unable to open all the way. "With calcification in blood vessels, a stent can help, but you can't do that with the aortic valve. Every organ in the body can be in perfect condition, but if the aortic valve stops functioning, that's the end of that life," said Mayandi Sivaguru, the first author of the paper and the director of the Cytometry and Microscopy to Omics Facility in the Carver Biotechnology Center. Despite the prevalence and biological importance, little is known about how the calcium deposits form or grow. Fouke's group has pioneered the field of "GeoBioMed," a combination of geology, biology and medicine, and previously applied it to the study of kidney stones. In the new study, published in the journal Scientific Reports, Fouke's group at Illinois teamed up with colleagues at the UCLA School of Medicine and the Jackson School of Geoscience at Texas to study and document the steps of calcium deposit formation in aortic valves from human cadaver hearts. "We used more than 12 modalities of study, including optical microscopy, electron microscopy and spectroscopy, to investigate the nature and progression of mineralization and protein localization in the aortic valve for the first time. This multimodal analysis set us apart, uncovering a new line of evidence to better understand cardiovascular calcification," Sivaguru said. The starting point is healthy leaflet tissue. Then tiny spherules of calcium phosphate form in the smooth muscle layer of the leaflets. Crucially, the team found that the form of calcium phosphate in the mineral deposits is not the same type as found in bone, called apatite, as has been widely thought. Instead, the deposits consist predominately of amorphous calcium phosphate, which has the ability to morphologically shapeshift and atomically rearrange. As they grow, the spherules coalesce into layers that encrust and stiffen the collagen and smooth muscle fibers that give the leaflets their flexibility. These processes combine to form large nodules that rotate, touch each other and further stiffen the tissues. "Immediately, we saw that the reactions within the tissues of the valves were virtually identical to those we've studied in coral reefs, hot springs and many other natural environments that harbor life-water-mineral interactions," said Fouke, who is the Ralph E. Grim Professor at Illinois. "Our blood is saturated with calcium and phosphate. Calcification of collagen and growth of nodules is inevitable given our blood chemistry, biology and composition. "However, the silver lining to all of this is that we also found that our body has evolved these incredibly intricate and effective processes to fight mineralization. It can't stop it, but it can slow it down dramatically." The researchers found two defense mechanisms. As the tiny ACP spherules form and begin to coalesce, the heart tissues produce large amounts of the protein osteopontin. Osteopontin promotes apatite growth and calcification in bones and kidney stones, so the findings initially puzzled the researchers, Fouke said. But osteopontin has the opposite, inhibitory effect on ACP, slowing down collagen calcification and nodule aggregation. "That's why knowing it's ACP instead of apatite is so important. Enhancing the release of osteopontin could be an important new target to slow down calcification to a level that it won't be a threat or require surgical intervention," Fouke said. The body's second defense is the very collagen where the nodules form. The researchers found that as the nodules start growing, the collagen fibers stretch around and contain them, forming a water barrier that further slows nodule growth. In addition to investigating possible therapeutic applications of osteopontin to slow calcification, the researchers also hope their work opens new avenues of investigation into preventing initial growth and dissolving already-formed mineral deposits throughout the human body. In collaboration with Mayo Clinic, the team is now applying their multimodal GeoBioMed approach to studying calcification in human breast tumors, a hallmark of the disease. The Barbara and Ed Weil Foundation, the National Institutes of Health (grant OT2OD023848) and the UCLA Amara-Yad project supported this work.

PARIS--(BUSINESS WIRE)-- Regulatory News: GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced its participation at key medical and stakeholder meetings in the remainder of 2024. On June 4, three papers on LUMEVOQ®, the company’s gene therapy for Leber Hereditary Optic Neuropathy (LHON, will be presented at the 16th Meeting of the European Neuro-Ophthalmology Society (EUNOS), which is being held in Rotterdam, the Netherlands, from June 3 - 6, 2024. Presentation: “Efficacy and Safety of Lenadogene Nolparvovec Gene Therapy for Leber Hereditary Optic Neuropathy in the Real-Life Setting” Type: Poster Presenter: Catherine Vignal, MD, Quinze-Vingts National Eye Hospital, Paris, France Time: Poster Session 1, Tuesday, June 4, 2024, from 1:00 - 2:00 pm CEST Location: Poster Area – Poster P-099 Presentation: “Meta-Analysis of Treatment Outcomes for Patients With m.11778G>A MT-ND4 Leber Hereditary Optic Neuropathy” Type: Poster Presenter: Nancy J. Newman, MD, Emory University School of Medicine, Atlanta, USA Time: Poster Session 1, Tuesday, June 4, 2024, from 1:00 - 2:00 pm CEST Location: Poster Area – Poster P-101 Presentation: “Ocular Post-Mortem Analyses with Histopathological and Molecular Assessments in LHON Following AAV2 Gene Therapy” Type: Poster Presenter: Valerio Carelli, University of Bologna and IRCCS Istituto delle Scienze Neurologiche, Ospedale Bellaria, Italy Times: Poster Session 1, Tuesday, June 4, 2024, from 1:00 - 2:00 pm CEST Rapid Fire Poster Session, Tuesday, June 4, 2024, from 3:12 – 3:18 pm CEST Locations: Poster Area – Poster P-093 and Willem Burger Zaal – Presentation S03-13, respectively Papers on LUMEVOQ®, the Company’s gene therapy for Leber Hereditary Optic Neuropathy (LHON), are also planned to be presented at two other major medical conferences this year: the 2024 Annual Meeting of the American Academy of Ophthalmology (AAO) and the 27th Annual Congress of the European Association for Vision and Eye Research (EVER). The dates and times of the presentations will be confirmed later. On June 5, Magali Taiel, Chief Medical Officer of GenSight Biologics, will speak at the 2nd Multi-Stakeholders Meeting on Clinical Trials for Inherited Retinal Diseases organized by the ERN-EYE, a European Reference Network dedicated to rare eye diseases. Dr. Taiel will also be a speaker at the 2024 Mitochondrial Disease Conference in October, an event organized by the patient advocacy group Mitocon and endorsed by the EURO-NMD, a European Reference Network for rare neuromuscular diseases. About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, LUMEVOQ® (GS010; lenadogene nolparvovec), an investigational compound that has not been registered in any country at this stage, was developed for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. View source version on businesswire.com: Contacts GenSight Biologics Chief Financial Officer Ivan Tortet itortet@gensight-biologics.com LifeSci Advisors Investor Relations Guillaume van Renterghem gvanrenterghem@lifesciadvisors.com +41 (0)76 735 01 31 Source: GenSight Biologics View this news release online at: