CDCA7L

The intricate dance of nature often unfolds in mysterious ways, hidden from the naked eye. At the heart of this enigmatic tango lies a vital partnership: the symbiosis between plants and a type of fungi known as arbuscular mycorrhizal (AM) fungi. New groundbreaking research delves into this partnership, revealing key insights that deepen our understanding of plant-AM fungi interactions and could lead to advances in sustainable agriculture. The intricate dance of nature often unfolds in mysterious ways, hidden from the naked eye. At the heart of this enigmatic tango lies a vital partnership: the symbiosis between plants and a type of fungi known as arbuscular mycorrhizal (AM) fungi. New groundbreaking research, recently published in the journal Science, delves into this partnership, revealing key insights that deepen our understanding of plant-AM fungi interactions and could lead to advances in sustainable agriculture. AM fungi live within plant root cells, forming a unique alliance with their plant hosts. This relationship is more than a simple coexistence; it involves a complex and critical exchange of nutrients essential for fungal survival and highly beneficial for the plant. Researchers at the Boyce Thompson Institute (BTI) have uncovered the roles of two proteins, CKL1 and CKL2, which are active only in the root cells containing the AM fungi. These two proteins belong to a larger family of proteins known as CKLs, whose functions in the plant have yet to be fully understood. "The closest relatives of the CKL family are proteins, called CDKs, that control the plant cell cycle and are located in the nucleus of the cell. Surprisingly, the CKL1 and CKL2 proteins have evolved a different role than CDKs -- they do not control the cell cycle. They are tethered to the membranes of the root cell, including a membrane that surrounds the fungus," said Dr. Sergey Ivanov, a post-doctoral researcher at BTI and first author of the study. The scientists found that these CKL proteins are critical for the fungi's survival within plant roots. They play a pivotal role in controlling the flow of lipids (fats) from the plant to the fungi, a process essential for the fungi's nourishment. Without these proteins, key genes that manage this lipid transfer are not activated, starving the fungi. The research also uncovered a complex web of interactions involving several receptor kinase proteins. One of these kinases is known for its role in allowing the AM fungus to penetrate the root's outer layer. The researchers discovered that this same kinase adopts a new role deeper within the root, where it partners with CKL proteins, potentially to initiate the flow of lipids to the fungus. Surprisingly, while CKL proteins are vital for controlling lipid flow, they don't manage the entire symbiotic lipid pathway. Instead, they control genes responsible for the start and end of this pathway. Meanwhile, a key protein operating in the middle of this pathway, RAM2, is activated by a different regulator, RAM1. For full-scale lipid production to occur, both the CKL and RAM1 pathways must be active. "Lipids are costly for the plant, so dual regulatory mechanisms may ensure that lipid provisioning is tightly controlled, perhaps a safeguard against exploitation by fungal pathogens," said Dr. Maria Harrison, a professor at BTI and senior author of the study. Harrison continued, "In an agricultural context, leveraging this natural symbiosis could lead to crops that are more efficient in nutrient uptake and more resilient to environmental stressors." This study not only deepens our understanding of the molecular dynamics behind plant-AM fungal symbiosis but also highlights the intricate and often unseen connections that sustain life on our planet. It's a reminder of the incredible complexity and interdependence found in nature, much of it hidden right beneath our feet. Funding for this research was provided by the US National Science Foundation Plant Genome Research Program.

ROCKVILLE, Md., Dec. 13, 2023 /PRNewswire/ -- On February 8, 2024, The Speak Foundation, a patient-led 501(c)(3) organization for Limb-Girdle Muscular Dystrophy (LGMD), will be convening a multi-stakeholder LGMD Scientific Drug Development Workshop in Rockville, Maryland. The workshop will continue to drive the momentum for the sense of urgency needed by the patient community to accelerate LGMD drug development. Continue Reading LGMD Scientific Drug Development Workshop The Speak Foundation logo Academic medical experts, senior leaders from the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), highly experienced drug developers, and other specialists will come together to discuss LGMD pathophysiology, clinical outcomes and patient-focused drug development, surrogate endpoints and the accelerated approval pathway. The meeting will focus on six LGMD subtypes: LGMD2A/R1, LGMD2B/R2, LGMD2C/R3, LGMD2D/R4, LGMD2E/R5, and LGMD2I/R9. "In September 2022, at the LGMD community's first Externally-Led Patient Focused Drug Development Meeting (EL-PFDD), the FDA heard perspectives of patients and caregivers on the health effects, daily impacts, treatment goals, and decision factors that would be considered when seeking out or selecting a treatment," explains Kathryn Bryant, founder of the Speak Foundation. "This workshop is a continuing step to work with the FDA and LGMD scientific leaders on pushing critical drug development forward. The time is now." LGMD Scientific Workshop session presenters will include CBER Director Dr. Peter Marks, and CDER's Office of New Drugs (OND) Director, Dr. Peter Stein. Other confirmed speakers include Dr. Jerry R. Mendell, retired attending neurologist of Nationwide Children's Hospital, Dr. Nicholas Johnson of Virginia Commonwealth University, Dr. Louise Rodino-Klapac of Sarepta Therapeutics, Dr. Douglas Sproule of ML Bio Solutions, a BridgeBio affiliate, Dr. Katherine Mathews of University of Iowa Health Care, Dr. Matthew Wicklund of University of Texas San Antonio, Dr. Peter Kang of University of Minnesota Medical School and Dr. Lindsay Alfano of Nationwide Children's Hospital. "As a translational clinician scientist, devoting a lifetime of work toward improving the lives of patients with muscular dystrophy, workshops like the LGMD Scientific meeting are important venues for discussing the current scientific understanding of LGMD and the implications for drug development." said Dr. Jerry R. Mendell. "Bringing key LGMD stakeholders together to share ideas and research findings in a public forum is the most productive way to find solutions and advance therapies that will improve the lives of LGMD patients." The LGMD Scientific Workshop will be a focused discussion with clinicians, scientific researchers, drug developers, regulators, patients and patient advocates on the characteristics of LGMD that drive drug development programs. The meeting will be held virtually and by invitation for in-person attendance. Proceedings will be recorded and shared with the broader patient and scientific communities through The Speak Foundation. More details will be added soon to: The Speak Foundation - Limb Girdle Muscular Dystrophy. About The Speak Foundation: The Speak Foundation is a 501(c)(3) nonprofit charity, which is focused on supporting patients living with all forms of LGMD and on facilitating development of treatments for these diseases. About Limb Girdle Muscular Dystrophy: Limb-Girdle Muscular Dystrophy (LGMD) is a group of muscular dystrophies caused by mutations in one of over 30 genes. The age of onset, symptoms, progression, and inheritance pattern varies among genetic subtypes, but generally result in severe disability and are often life-threatening due to cardiac and respiratory complications. There are estimated to be some 20,000+ people living with a form LGMD in the United States. Media Contact: Rachel DeConti [email protected] 860-209-0492 SOURCE The Speak Foundation

CAMBRIDGE, MA, USA I February 17, 2023 I Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the first patient has been dosed in Study SRP-9003-102. Also known as VOYAGENE, Study 9003-102 is a phase 1 study of SRP-9003 (bidridistrogene xeboparvovec) for the treatment of limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E). VOYAGENE is a U.S.-only study enrolling ambulant patients aged 18 years or older and non-ambulant patients, ages 4-50 years, using clinical process SRP-9003 material. “Sarepta has previously disclosed positive expression and function data from our initial clinical study, Study SRP-9003-101, exploring multiple doses of SRP-9003 in a younger, ambulant population. The VOYAGENE study, which also utilizes clinical material, provides an opportunity to generate additional data in a broader population of patients while we finalize plans for a global, Phase 3 study using commercially representative process material that we intend to begin later this year,” said Louise Rodino-Klapac, Ph.D., executive vice president, chief scientific officer and head of research and development, Sarepta Therapeutics. “Sarepta is applying lessons from across our gene therapy portfolio to help advance the development of our investigational LGMD programs as efficiently as possible. Current treatments for LGMD are limited to symptom management and we remain fully committed to working with urgency to bring forward new treatments that can slow the progression of this disease, improve mobility and enhance the quality of life for individuals living with LGMD2E and other LGMD subtypes.” More information on the VOYAGENE study is available at https://genesislgmd.com/study/voyagene . About SRP-9003 (bidridistrogene xeboparvovec) SRP-9003 (bidridistrogene xeboparvovec) is an investigational gene therapy that uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. SRP-9003 also uses the MHCK7 promoter, chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications. About Limb-girdle Muscular Dystrophy Limb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begins in muscles around the hips and shoulders before progressing to muscles in the arms and legs. Sarepta’s six LGMD gene therapy programs in development include LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, LGMD2B/R2, LGMD2L/R12 and LGMD2A/R1, which together represent more than 70 percent of known LGMD cases. Patients with LGMD2E begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E. About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter , LinkedIn , Instagram and Facebook . SOURCE: Sarepta Therapeutics