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Research Projects
Supporting Research for Lesch-Nyhan
Love Never Sinks is dedicated to advancing research for Lesch-Nyhan. We raise funds through various initiatives, including our annual Million Dollar Bike Ride, which is generously matched by the ODC up to $30,000. Your donation can help support our efforts to fund groundbreaking research projects that are making a significant impact on the lives of individuals living with Lesch-Nyhan .
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Simply text SCIENCE to 53-555 to support our research efforts and help us improve the lives of individuals with Lesch-Nyhan.
Feb 1, 2025
Exploring the profile of Extracellular Vesticles (EV’s) in Lesch-Nyhan Syndrome (LNS)
Feb 1
Awardee: Giulia Bernardini
Institution: Universita degli Studi di Siena, Departimento di Biotecnologie, Chimica e Farmacia
Grant Amount: $57,332
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Understanding Lesch-Nyhan Syndrome Through Tiny Messengers Lesch-Nyhan Syndrome (LNS) is a very rare genetic disease that mainly affects boys. It causes severe neurological problems, including involuntary movements and self-injury, as well as high levels of uric acid in the blood, which can lead to kidney stones. The current treatment can only help to lower the uric acid levels, but these cannot cope up with neurological and behavioural problems. While we know a lot about the disease, many aspects of how it affects the brain remain a mystery. Our project focuses on tiny particles called extracellular vesicles (EVs). These are small packages released by cells that carry important messages in the form of proteins, fats, and genetic material. They help cells communicate with each other, and in brain diseases, they may play a role in how the disease develops. We aim to develop new ways to study EVs in the blood of people with LNS. By doing this, we hope to: -Understand how EVs contribute to the brain and body changes in LNS. -Identify specific markers in EVs that are unique to LNS, which could help us develop better treatments. -Lay the groundwork for creating therapies that use EVs to target the disease directly. This research could not only improve the understanding of LNS but also open the door to new treatments for this challenging and neglected disease.
Feb 1, 2024
Unravelling HGprt functioning in fore- and midbrain development using brain organoids
Feb 1
Awardee: Sharon Kolk
Institution: Radboud University, Donders Institute for Neuroscience
Grant Amount: $68,367.00
Funding Period: February 1, 2024 - January 31, 2025
Summary:
LND is an incapacitating disease characterized by a neurobehavioral phenotype, cognitive deficits and self-injurious behavior caused by HPRT1 gene mutation(s). LND is specifically associated with a reduction of dopamine in the brain. Recently, we reported that proliferation and migration patterns of developing midbrain dopamine (mDA) neurons are disrupted in absence of the gene, resulting in abnormal brain development in an LND animal model. To dissect the role of the causative gene in human fore- and midbrain development, we intend to investigate human-specific brain organoids using patient-derived induced pluripotent stem cell (iPSC) lines carrying HGPRT loss-of-function (LOF) mutations, age-matched control lines as well as edited control lines carrying HGPRT mutations. In addition, assembloids -fusions of dorsal forebrain organoids and midbrain organoids- will be generated in various combinations of control versus LOF tissue at multiple time points. It is furthermore shown that folic acid plays a role in purine metabolism and that physiological levels lead to metabolite accumulation in LND patients. Therefore, we will add various concentrations to the culture medium of both the fore-as well as the midbrain organoids at multiple developmental timepoints. Eventually this will give us insight into the developmental time window where we can, either genetically or pharmacologically, intervene in the future to alleviate particularly the behavioral and/or cognitive characteristics associated with LND.
Feb 1, 2023
Dopamine in Lesch-Nyhan Disease
Feb 1, 2023
Awardee: Jasper Visser
Institution: Radboud University Medical Center, Nijmegen, The Netherlands
Grant Amount: $85,779.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
In Lesch-Nyhan disease (LND), it is unknown why the loss of a very generic protein that is present in all cells of the body causes such a specific brain dysfunction with abnormal movements and self-injury. It is thought that brain cells that use the neurotransmitter dopamine to pass on signals to other brain cells are particularly affected in LND, but it is not known whether these are the only brain cells that are affected. This project investigates in a mouse model for LND whether repairing these dopamine neurons alone would be sufficient to prevent or treat the brain abnormalities in LND. If that is the case, they could serve as the primary target for future therapies.
Publications:
Very Early Levodopa May Prevent Self-Injury in Lesch-Nyhan Disease
April 2023 Update
Our project that is supported by the 2022 ODC Million Dollar Bike Ride investigates what goes wrong during brain development and Lesch-Nyhan Disease and which types of brain cells need to be rescued. In a mouse model for Lesch-Nyhan disease we repair specific types of brain cells during the development of the embryo, and then investigate the effects thereof brain development—particularly whether this is sufficient to treat (or prevent) the development of brain abnormalities that would otherwise occur. From these results, we will learn a) more about the mechanisms behind the neurological symptoms in Lesch-Nyhan disease b) about the potential targets for future therapies and see about the optimal timing during brain development for future therapies. Currently, we are investigating the effects of these repair attempts under the microscope. It will take another few months before we have the first results.'
The ODC MDBR Pilot Grant Program provides a one-year grant to support research related to a rare disease represented in the 2025 Million Dollar Bike Ride. Number of awards and dollar amounts vary per disease based on fundraising totals by each disease team.
Eligibility
This RFA is open globally. International applicants are invited to apply. All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA. Prior MDBR award recipients must have current and updated project reporting to be eligible for selection.
Letter of Interest Instructions:
Please follow for more information
MILLION DOLLAR BIKE RIDE
PILOT GRANT PROGRAM
