Premature aging syndrome

New Trial to Study Progerinin Treatment for Ultra-Rare Condition BUSAN, KOREA; PEABODY, MA; and GERMANTOWN, MD / ACCESSWIRE / October 2, 2024 / The United States Food and Drug Administration (FDA) has authorized the start of patient enrollment for a Phase 2a clinical trial of Progerinin, an investigational drug being developed for the treatment of Progeria. Advancing the development of Progerinin could potentially provide an additional treatment for this fatal disease. PRG Science & Technology logo Hutchinson-Gilford Progeria Syndrome (“Progeria”) is an ultra-rare, genetic, “rapid-aging” condition affecting approximately 1 in 18 million people. Without treatment, children with Progeria die of heart disease at an average age of 14.5 years old. Progeria is caused by a random genetic mutation that produces an overabundance of the toxic protein, progerin. The accumulation of progerin occurs with aging in the general population, in the cardiovascular system and elsewhere in the body, such as the skin. In children and young adults with Progeria, the rate of progerin accumulation is highly accelerated, resulting in progressive cellular damage and atherosclerotic heart disease. Progerinin was developed by Korean-based biotech company PRG Science & Technology Co., Ltd. (PRG S&T) with research funding from The Progeria Research Foundation (PRF). The trial is a collaborative effort between PRG S&T, PRF, and trial site Boston Children’s Hospital, and will be managed by contract research organization Amarex. In the Phase 2a randomized open label trial, Progerinin will be administered in combination with the current standard-of-care, Zokinvy, to 10 patients with Progeria and Progeroid Laminopathies (PL) who are one year of age and older. Zokinvy has been shown to increase lifespan in a Progeria mouse model by 25%, and data published in the journal Cells in April 2023 indicated that Progerinin showed a potential increase in Progeria mouse lifespan by 50%. Zokinvy works by blocking the toxic, disease-causing protein, progerin, from developing and attacking normal cells, while Progerinin appears to reduce the level of progerin that accumulates in the body. Currently, Zokinvy is the only treatment for Progeria and PL approved by the FDA (in 2020), the European Medicines Agency (EMA, in 2022) and the Japanese Ministry of Health, Labor and Welfare (MHLW, in 2024). “Since its establishment, PRG S&T has focused on developing rare genetic disease treatments. This clinical trial demonstrates PRG S&T’s R&D capabilities to improve access to new drugs and expand treatment opportunities for children with progeria worldwide,” said Bumjoon Park, president of PRG S&T. “PRG S&T will focus on R&D and technological innovation to accelerate the development of treatments, including preparation for follow-up clinical trials, and lead to the development of new drugs.” “This new trial represents another step forward in our mission to treat and cure these amazing children and young adults with Progeria,” said PRF Executive Director Audrey Gordon, Esq. “Each Progeria clinical trial builds on learnings from our previous trials, so that we are continually making progress toward even better treatments and the cure. Most importantly, we are grateful for the courage and resilience of these children and young adults with Progeria and their families for participating in research programs and contributing to this important mission.” “Patients with Progeria and their families deserve more options,” said Dr. Kush Dhody, President, Amarex Clinical Research. “This is an especially devastating diagnosis given the shortened lifespan it causes. We’re honored to support a study that brings more hope to these patients.” About Progeria Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), and PL are ultra-rare, multisystemic, premature aging diseases that accelerate mortality in young patients. Progeria is caused by a genetic mutation in the LMNA (“lamin A”) gene, and results in a disease-causing abnormal protein called progerin. There are approximately 400-450 children and young adults worldwide with Progeria. Thanks to PRF-funded research, we now know that progerin is produced in all of us as we age, but at a much lower rate than in children with Progeria. Due to this discovery of the biological connection between Progeria, heart disease and aging, finding the cure for one of the rarest diseases on earth could provide keys for treating millions of adults with heart disease and stroke associated with the natural aging process, as well as help the entire aging population. About PRG Science & Technology Co., Ltd. PRG S&T is a research & development company specializing in the treatment of rare genetic diseases. PRG S&T has been developing therapeutics for rare genetic diseases (laminopathies, neurodegenerative diseases, neuro-oncology etc.) with small molecules, which are derived from target sites on aberrant Protein-Protein Interactions (PPI). All four pipelines currently in PRG S&T’s possession have been designated as orphan drugs by the US FDA. Progerinin, the investigational treatment for Progeria has been approved by the FDA to enter phase 2 clinical trials, and is about to enter Phase2 at Boston Children’s Hospital. The non-clinical study of PRG-N-01, the treatment for neurofibromatosis type2, has been completed. IND for Phase I/II of PRG-N-01 has been approved by the Korea FDA and has been administered to patients at Asan Medical Center (South Korea) in June 2024. If these two drugs, Progerinin and PRG-N-01, are developed successfully, they are expected to become first-in-class innovative new drugs. For more information, please visit . About The Progeria Research Foundation The Progeria Research Foundation (PRF) was established in 1999 by the family of Sam Berns, a child with Progeria. Within four years of its founding, the PRF Genetics Consortium discovered the Progeria gene, a collaboration led by Dr. Francis Collins, former Director of the National Institutes of Health (NIH). PRF has funded and co-coordinated all lonafarnib-associated clinical trials for Progeria and Progeroid Laminopathies, conducted at Boston Children’s Hospital, and supports scientists who conduct Progeria research worldwide. PRF’s International Patient Registry includes over 370 children with Progeria in 70 countries. PRF is the only non-profit organization solely dedicated to finding treatments and the cure for Progeria and its aging-related conditions, including heart disease. The organization fills a void, putting these children and Progeria at the forefront of scientific efforts. For more information and to support PRF’s mission, please visit . About Amarex Clinical Research, LLC, an NSF company Amarex Clinical Research, LLC, is a global, full-service Contract Research Organization (CRO) with significant expertise conducting biomedical research. The leadership team’s combined experience includes the design and conduct of several hundred clinical research projects in many therapeutic indications. Amarex provides services in Project Management: Phase I-IV, BE/BA, PK/PD; Regulatory Affairs: FDA Applications and meetings, applications to International Health Authorities, GxP Compliance Audits; Clinical Operations; Adaptive Study Designs; Statistical Analysis; Data Management; Medical Monitoring; Safety and Pharmacovigilance; and General Consulting. Amarex can take your product through the entire approval process, from creating the regulatory approval strategy, to conducting trials, to writing the marketing approval application. Join our growing list of clients with approved products assisted by quality, cost-efficient services. For more information visit . Contact Information Eleanor Maillie PRF emaillie@progeriaresearch.org 978.879.9244 Sunghee Kim PRG S&T shkim@prgst.com Kalli DeWeese Amarex kdeweese@nsf.org Related Images PRG Science & Technology logo Amarex Clinical Research logo PRF logo SOURCE: The Progeria Research Foundation View the original press release on newswire.com.

Researchers have discovered the connection between aldehydes, organic compounds produced by cells as part of metabolic processes, and rapid aging. Their findings indicate a potential treatment for diseases that lead to accelerated aging as well as a means to counteract aging in healthy people by controlling exposure to aldehyde-inducing substances including alcohol, pollution, and smoke. A team of researchers at Nagoya University in Japan has discovered that aldehydes are metabolic byproducts associated with premature aging. Published in Nature Cell Biology, their findings reveal insights into premature aging diseases and potential strategies to combat aging in healthy individuals such as controlling exposure to aldehyde-inducing substances including alcohol, pollution, and smoke. A person's health can be harmed by aldehydes. However, the group's findings suggest these detrimental effects also include aging. The team who made this discovery included Yasuyoshi Oka, Yuka Nakazawa, Mayuko Shimada, and Tomoo Ogi of Nagoya University. "DNA damage is linked with aging phenotypes," said Oka. "However, for the first time, we propose a relationship between aldehyde-derived DNA damage and premature aging." The researchers hypothesized that there might be a link between aldehydes and aging since individuals with premature aging disorders, like AMeD syndrome, exhibit inadequate activity of enzymes, like ALDH2, that break down aldehydes. For healthy individuals, ALDH2 is also important in our response to alcohol. When a person drinks wine or beer, the liver metabolizes the alcohol into aldehydes so it can be eliminated from the body. The activity of ALDH2 is important for converting the aldehydes into a non-toxic substance. Aldehydes are harmful because they are highly reactive with DNA and proteins. In the body, they form DNA-protein crosslinks (DPCs) that block important enzymes in typical cell proliferation and maintenance processes, causing these processes to malfunction and the patient to age. Focusing on DPCs caused by aldehyde, the scientists used a method called DPC-seq to investigate the link between aldehyde accumulation and DNA damage in premature-aging disease patients. In a series of experiments, the researchers discovered that the TCR complex, VCP/p97, and the proteasome are involved in the removal of formaldehyde-induced DPCs in actively transcribed regions. This was confirmed by a mouse model lacking both aldehyde clearance processes and the TCR pathway that showed worse AMeD syndrome symptoms. These processes are important because they are related to the clearance of aldehydes. It suggests an association between premature aging diseases and aldehyde accumulation. Professor Ogi is hopeful about the implications of their findings, stating: "By elucidating the mechanism by which DNA damage heals quickly, we have revealed part of the cause of genetic premature aging." "Our research opens up new avenues for understanding the underlying mechanisms of premature aging diseases and offers potential targets for therapeutic intervention," Oka said. "By elucidating the role of aldehydes in DNA damage and aging, we are paving the way for future studies aimed at developing novel treatments and interventions." He continued: "The development of therapeutic drugs has not progressed because we have not fully understood the causes of AMeD syndrome and Cockayne syndrome. This study suggests that the patient's pathological condition is related to DPC derived from aldehydes generated within cells. These results are expected to help in the search for compounds that remove aldehydes, thus aiding in the formulation of therapeutic drug candidates." This research has implications that extend beyond genetic diseases, as their findings suggest that aldehyde-induced DNA damage may play a role in the aging process in healthy individuals too. By pinpointing aldehydes as substances that contribute to aging, this study sheds light on the intricate connection between environmental factors and cellular aging. This may have significant implications for human health and lifespan.

The Progeria Research Foundation Marks Significant Achievement as Zokinvy™ (lonafarnib) Receives Japanese Approval for the Treatment of Progeria and Processing-Deficient Progeroid Laminopathies PEABODY, Mass., Jan. 20, 2024 /PRNewswire/ -- The Progeria Research Foundation (PRF) today announced a new milestone with the approval of Zokinvy™ (lonafarnib) by the Japanese Ministry of Health, Labor and Welfare (MHLW), for the treatment of Progeria and processing-deficient Progeroid Laminopathies (PL). Progeria is an ultra-rare, fatal pediatric "rapid-aging" disease. PRF, a pioneer in the rare disease research foundation space, has led Zokinvy clinical trial research since 2007. Eiger BioPharmaceuticals (Eiger) and PRF began a partnership in 2018 to bring this drug to market. Approval from the U.S. Food and Drug Administration (FDA) for Zokinvy was granted in November, 2020 and the European Medicines Administration (EMA) in July, 2022. Zokinvy is a farnesyltransferase inhibitor (FTI) that has shown survival benefit in children with Progeria. Data based on information from the PRF International Patient Registry and clinical trials co-coordinated by PRF and Boston Children's Hospital (BCH) demonstrated that in patients with Progeria, Zokinvy reduced the incidence of mortality by 72% and increased average survival time by an average of 30% (4.3 years). Without Zokinvy treatment, children with Progeria die of heart disease at an average age of 14.5 years. Prevalence data from PRF's International Patient Registry indicate an expected 6 children with Progeria are living in Japan today. "We're thrilled by this wonderful news," said Audrey Gordon, President and Executive Director of The Progeria Research Foundation. "On the heels of the 2020 FDA approval and the 2022 EMA approval for Zokinvy, now children and young adults with Progeria and PL in Japan will be able to access this life-extending, heart-strengthening treatment through the convenience of a prescription." "Since co-founding The Progeria Research Foundation in 1999, we have poured our hearts and souls into the most promising research toward treatments and the cure for every child with Progeria," said Leslie Gordon, MD, PhD, PRF Medical Director and Zokinvy Clinical Trial Investigator. "After more than a decade of Zokinvy research funded by PRF and co-conducted by PRF and BCH, Zokinvy's authorization in Japan is a win for the worldwide Progeria community. Thank you to the courageous children, their families, and our many expert Progeria research teams and pharmaceutical partners who made this key milestone possible." Over the course of its 24-year existence, PRF has made tremendous strides toward its mission to discover the cause, treatments and cure for Progeria. In partnership with the National Institutes of Health (NIH), PRF was the driving force behind the 2003 Progeria gene discovery. PRF holds bi-annual scientific workshops, funds research grants breaking new ground in areas such as RNA therapeutics and Genetic Base Editing, and funds clinical drug trials. PRF's core patient-focused programs include the Progeria International Patient Registry, Medical & Research Database, Cell & Tissue Bank, Diagnostics Testing Program, and a Clinical Care Handbook for families and physicians. "After conducting 16 years of Progeria clinical trials at Boston Children's Hospital, this milestone demonstrates the positive impact of a dedicated research team, rigorous testing, and the steadfast bravery of the wonderful children and their families," said Dr. Monica Kleinman, Principal Investigator for the Progeria clinical trials at Boston Children's Hospital. "Being a part of this achievement for these children is not only professionally rewarding but also a testament to the transformative potential of scientific advancement in Progeria research." About Progeria Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), and PL are ultra-rare, multisystemic, premature aging diseases that accelerate mortality in young patients due to accumulation of cellular progerin in HGPS or an abnormal lamin A protein in PL. Progeria is caused by a genetic mutation in the LMNA ("lamin A") gene, and results in a disease-causing abnormal protein called progerin. There are approximately 400-450 children worldwide with Progeria. Thanks to PRF-funded research, we now know that progerin is produced in all of us as we age, but at a much lower rate than in children with Progeria. Due to this discovery of the biological connection between Progeria, heart disease and aging, finding the cure for one of the rarest diseases on earth could provide keys for treating millions of adults with heart disease and stroke associated with the natural aging process, as well as help the entire aging population. About The Progeria Research Foundation The Progeria Research Foundation (PRF) was established in 1999 by the family of Sam Berns, a child with Progeria. Within four years of its founding, the PRF Genetics Consortium discovered the Progeria gene, a collaboration led by Dr. Francis Collins, Acting Science Advisor to the President of the United States and former Director of the National Institutes of Health (NIH). PRF has funded and co-coordinated all Zokinvy-associated clinical trials for Progeria and Progeroid Laminopathies, conducted at Boston Children's Hospital, and supports scientists who conduct Progeria research worldwide. PRF's International Patient Registry includes over 370 children with Progeria in 70 countries. PRF is the only non-profit organization solely dedicated to finding treatments and the cure for Progeria and its aging-related conditions, including heart disease. The organization fills a void, putting these children and Progeria at the forefront of scientific efforts. For more information and to support PRF's mission, please visit . SOURCE Progeria Research Foundation