National Institute of Child Health & Human Development

Researchers from the Francis Crick Institute and the UCL Queen Square Institute of Neurology have found a way to selectively target cells affected by motor neurone disease (MND). Published in the journal Science , the study details how the team developed DNA molecules that contain ‘invisibility cloak’ sequences, which can only be removed by diseased cells. It is hoped that preventing healthy cells from reading the molecules’ messages could lead to safer and more effective gene therapies for MND, as well as other neurodegenerative diseases, including frontotemporal dementia. “While neurodegenerative diseases have devastating effects, we can estimate that less than 0.00001% of cells in a patient’s body are actually diseased,” explained study lead Oscar Wilkins. “The challenge is finding a way to specifically target treatments to this minuscule fraction of diseased cells, while avoiding unnecessary treatment of the 99.99999% of cells which are healthy,” he said. Affecting up to 5,000 adults in the UK at any one time, MND is a rare condition that progressively damages parts of the nervous system and leads to muscle weakness, often with visible wasting. The team’s new approach centres around the activity of the TDP-43 protein, which resides near the DNA in healthy cells and helps them to correctly interpret the DNA’s genetic instructions. However, this protein gets stuck in distant parts of diseased cells, corrupting their interpretation of genetic messages. Using artificial intelligence prediction tools and careful design, the researchers created DNA sequences that behave in the opposite way – the messages from the DNA are corrupted in healthy cells, but can be interpreted correctly in diseased ones. Pietro Fratta, head of the molecular neurodegeneration laboratory at the Crick and UCL, who co-invented the approach, said: “We hope this new technology will enable much bolder therapeutic approaches for MND. “Many potential therapies also alter important cellular processes and this may cause toxicity. Therefore, limiting their action to diseased cells, while leaving healthy cells untouched, will increase the safety of gene therapies and allow researchers to pursue many more treatment options.” US collaborators from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development also contributed to the therapeutic approach. Work to further develop gene therapies for amyotrophic lateral sclerosis, the most common form of MND, using the system is being supported by the Crick Translation Fund and by the UCL Neurogenetics Therapy Programme.

NICHD to Support Evaluation of Copper Release Characteristics of 3D-001in a Preclinical Model, as Company Prepares for Phase 1 Clinical TrialMANSFIELD, Mass., Sept. 25, 2024 (GLOBE NEWSWIRE) -- 3Daughters, Inc., a clinical development company fueling evolutionary healthcare for women, announced the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) will support testing to evaluate 3Daughters’ novel frameless, magnetic, copper intrauterine device (IUD) for female contraception at NICHD’s Biological Testing Facility. The facility supports research for the optimization of male and female contraceptive agents, particularly biologic studies for preclinical development and advancement. "We are incredibly honored to receive this support from the NIH at this point in our clinical development, which reaffirms the transformative potential of our frameless, magnetic copper IUD for female contraception," commented Mary Beth Cicero, CEO of 3Daughters. "We are committed to women’s health innovation, and to offering a new contraceptive option that meets the needs of women. With all the media exposure surrounding IUD insertion pain, our integrated system of an IUD and Slider™ (inserter/retriever) is directed to literally address the ‘pain points’ women experience with current IUDs. We are continuing to advance our program for 3D-001 and are poised to be in the clinic next year.” William Bracken, PhD, Head of Toxicology at 3Daughters and Primary Investigator for the study, stated, "This preclinical research will provide essential data on the copper release kinetics and inflammatory responses of 3D-001 compared to existing copper IUDs. We expect to significantly add to our understanding of how copper functions as a spermicide and potentially how a frameless design could be beneficial compared to the traditional T-shaped devices." The 3Daughters IUD is comprised of three small ellipses encased in copper that self-assemble into a stable triad formation upon insertion into the uterus. The triad is expected to float gently in the uterus, not requiring placement between the fallopian tubes like the T-shaped IUDs. The free-floating nature of 3D-001 could be important for copper release characteristics and product performance. Ms. Cicero further added, “We would like to acknowledge the foresight of NICHD in having a program for early-stage contraceptive testing.” 3Daughters is raising a Series A of $15 million to fund a Phase 1 clinical trial and is preparing to submit an IND in 2025. About 3Daughters™3Daughters is a clinical development company focused on evolutionary healthcare for women where cutting-edge research and innovation is desperately needed. The Company’s technology platform is based on physics and geometry to deliver targeted therapy to the uterus. The first product, (3D-001), is a frameless, magnetic, non-hormonal intrauterine device (IUD) for long-acting contraception that conforms to a woman’s body. Combined with our unique, patented Slider™ system (for insertion and retrieval), this integrated system is expected to eliminate the most painful steps in the insertion process as well as the nuisance factor of strings (needed for removal). 3Daughters’ vision is to solve health issues for women, particularly significant, and neglected, problems. 3Daughters plans to radically disrupt the IUD market by addressing the major adoption barrier — insertion pain. This pain is associated with all current rigid, plastic T-shape framed IUDs and prevents women from selecting one of the most effective forms of birth control. Visit 3daughtershealth.com for more information.

McLEAN, Va., Sept. 18, 2024 (GLOBE NEWSWIRE) -- Thought Leadership & Innovation Foundation (TLI), a not-for-profit organization that works at the nexus of science, technology and public health, today announces the transfer of ownership of the Limb Loss and Preservation Registry (LLPR®) from the National Institute of Child Health and Human Development (NICHD) to TLI. This landmark decision, approved by NICHD, underscores TLI's commitment to driving transformative change in healthcare and validates the level of public confidence in TLI capabilities for assuming the management of this vital project. “Established in 2018 under an IDIQ Contract funded by the National Institutes of Health (NIH), the LLPR has been instrumental in measuring and reporting patient data to enhance limb loss and limb difference treatment as well as preservation efforts nationwide,” says Shawn Murphy, vice president, TLI and former program manager for LLPR under NICHD and Mayo Clinic. Murphy continues, “With this transfer of ownership, TLI is poised to further the LLPR's mission of improving the quality, safety, effectiveness and cost of limb loss and limb difference treatment and preservation. We are honored to steward the LLPR into this new chapter.” A centralized data warehouse, the LLPR plays a crucial role in addressing public health knowledge gaps, refining rehabilitation approaches and guiding the development of functional devices for people with limb loss and limb difference. As part of TLI, the Registry will maintain its multi-stakeholder model, fostering collaboration among care providers, care sites, payers, device manufacturers, suppliers and regulatory agencies. “This transition marks a significant step forward in our collective efforts to drive healthcare innovation and improve outcomes for individuals facing limb loss and limb difference,” says Cass Isidro, president, Amputee Coalition. “Together, we will continue to provide valuable resources and support to individuals who have limb loss and limb difference, empowering them to live life fully and ensuring that no on faces the challenges and complexities of their journeys alone.” To support the LLPR in its mission to improve outcomes for individuals living with limb loss and limb difference, please click here. Your contribution directly impacts the quality of care and functional outcomes for the LLPR community. About TLIThe Thought Leadership & Innovation Foundation (TLI) is a not-for-profit organization that works at the nexus of science, technology and public health, innovating for superior prevention, treatment and outcomes for those facing life-altering medical diagnoses. TLI helps patients across the country and around the world find better healthcare outcomes. Visit www.thoughtfoundation.org and follow us on LinkedIn. About The Amputee Coalition: The Leading Voice on Limb Loss and Limb DifferenceThe Amputee Coalition is the only national nonprofit that serves all individuals who experience limb loss or limb difference. We are dedicated to ensuring that no one faces limb loss alone. Our mission is to support, educate, and advocate for people impacted by limb loss and limb difference. We work to provide vital resources to people with limb loss and limb difference, as well as their families and caregivers. With these resources, they can recover, readjust, and live the life they most want to live. Learn more at www.amputee-coalition.org.