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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 .

Your donation can make a difference!

Simply text SCIENCE to 53-555 to support our research efforts and help us improve the lives of individuals with Lesch-Nyhan.

The ODC MDBR Pilot Grant Program provides a one-year $57,322 grant to support research related to a rare disease represented in the 2024 Million Dollar Bike Ride. Number of awards and dollar amounts vary per disease based on fundraising totals by each disease team.

Eligibility

This $57,322 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 visit our website to submit your Letter of Interest (LOI), which can also be found here. This one-page LOI is due no later than Friday, September 20, 2024 by 8pm (EST).

ORPHAN DISEASE CENTER

MILLION DOLLAR BIKE RIDE

PILOT GRANT PROGRAM

Grant Awardee To be Announced:

Feb 1, 2024

Unravelling HGprt functioning in fore- and midbrain development using brain organoids

MDBRLNS

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.

MDBRLNS2023-1

Feb 1, 2023

Dopamine in Lesch-Nyhan Disease

MDBRLNS

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

MDBRLNS2022-1

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.'