COMBINEDBrain
COMBINEDBrain is a non-profit consortium of patient advocacy groups for rare, genetic neurodevelopmental disorders. They facilitate collection of patient samples for researchers to identify biomarkers to be used to treat and/or develop treatments.
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Contact united@renusyndrome.org to set up a call.
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What is the RSU biorepository program?
ReNU Syndrome United is developing a centralized collection of samples from individuals with ReNU syndrome and, when possible, unaffected family members.
RSU partners with the COMBINEDBrain Biorepository, which provides the infrastructure to coordinate collection, processing, storage, and research access. Samples are collected under an Institutional Review Board-approved protocol.
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COMBINEDBrain offers participation via the following options. Click here to learn more about each.
ReNU Syndrome United helps facilitate collection through these methods:
Roadshows - sample collection events held at patient conferences and community gatherings. These events bring trained collection teams to a single location, allowing families to contribute samples in a convenient and supportive environment while connecting with others in their community.
Scheduled home collection - mobile phlebotomy services; a trained professional visits the participant’s home to collect samples and arrange shipment to the biorepository.
This option allows families to participate even if they are unable to travel.
Coordinated physician-based collection - samples may be collected during routine clinical care or scheduled medical procedures performed by a participant’s physician. Examples may include cerebrospinal fluid (CSF) or tissue biopsies.
Arrangement of a post-mortem tissue donation - brain and other tissue samples may provide important insights that can help researchers better understand neurological conditions and guide future discoveries.
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By contributing biospecimens to the COMBINEDBrain Biorepository, participants help researchers better understand neurological disorders and accelerate the development of new treatments.
Medical records help researchers understand what ReNU syndrome looks like. Biospecimens help them investigate what is happening inside the body’s cells and biological systems.
This is especially important for RNU4-2. The gene produces U4 small nuclear RNA, an essential part of the spliceosome, which helps cells correctly process RNA. Pathogenic RNU4-2 variants can disrupt this process. To understand these changes and explore ways to correct them, researchers need access to well-characterized blood, plasma, cerebrospinal fluid, living cells, and laboratory cell models from individuals with ReNU syndrome.
Participation is always voluntary, and every family should make the decision that feels right for them.
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Legal adults diagnosed with the capacity to consent for yourself
Parent/legal guardian of a minor with a rare genetic neurodevelopmental disorder
Parent/legal guardian of an adult with a rare genetic neurodevelopmental disorder who cannot give consent
Parent/legal guardian of a minor who is related to someone with a rare genetic neurodevelopmental disorder, to be used as a control
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RSU is still in the early stages of launching the biorepository and costs are still being assessed.
If you are interested in sponsoring costs of the biorepository, sample collection, or distribution, contact us at united@renusyndrome.org.
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united@renusyndrome.org
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Why does RNU4-2 research need biospecimens if researchers already know the genetic variant?
A genetic report identifies the change in RNU4-2, but it cannot fully show what that change does inside a person’s cells.
Biospecimens can help researchers investigate:
How RNU4-2 variants alter RNA splicing
Which genes and biological pathways are affected
Whether different variants produce different cellular effects
Why individuals may experience different features or levels of severity
Whether measurable biomarkers could track ReNU syndrome or treatment response
Whether potential therapies correct the underlying cellular changes
Which samples are the highest priorities for RNU4-2 research?
RSU’s current highest-priority research materials include:
Whole blood: Blood can provide DNA and RNA for genomic and splicing studies. It can also be processed to obtain plasma and peripheral blood mononuclear cells, or PBMCs.
Plasma: Plasma contains circulating proteins, metabolites, immune markers, and extracellular vesicles. Researchers may use these to search for biomarkers that reflect biological changes associated with ReNU syndrome or could eventually help measure treatment response.
Cerebrospinal fluid, or CSF: CSF surrounds the brain and spinal cord. Because ReNU syndrome primarily affects neurodevelopment, CSF may provide valuable information about proteins, metabolites, and other biological signals that more closely reflect the central nervous system.
Fibroblasts: Fibroblasts are living cells generally obtained through a small skin biopsy. Researchers can study RNA splicing and cellular function directly in these cells or use them to create induced pluripotent stem cells.
Induced pluripotent stem cells, or iPSCs: iPSCs are renewable laboratory cell lines typically created by reprogramming blood-derived cells or fibroblasts. Researchers can develop them into neuron-like cells and other relevant cell types to study brain development, model ReNU syndrome, and test possible therapeutic approaches.
Brain tissue removed during epilepsy surgery: When epilepsy surgery is medically necessary, brain tissue already being removed as part of the procedure may provide an especially valuable opportunity for research. It allows scientists to study RNU4-2-related RNA splicing and cellular changes directly in human brain tissue and may help them investigate the biology underlying seizures in ReNU syndrome.
Can one blood collection provide several research materials?
Potentially. When collected and processed correctly, one blood draw may provide whole blood, plasma, DNA, RNA, and PBMCs. PBMCs can be studied directly, stored as living cells, or potentially used to generate iPSCs.
Because different tubes and processing methods are required, families should coordinate collection through RSU and COMBINEDBrain. Please do not independently collect or ship a sample.
Why are iPSCs especially valuable?
Researchers cannot often directly collect brain cells from a living participant. iPSCs provide another option.
Scientists can develop iPSCs into neuron-like cells and other cell types that may be relevant to ReNU syndrome. These models can help researchers:
Observe how RNU4-2 variants affect developing cells
Study abnormal RNA splicing in disease-relevant cell types
Compare different RNU4-2 variants
Test whether an experimental therapy corrects cellular changes
Evaluate possible safety concerns before a treatment reaches people
Because iPSCs can continue growing in the laboratory, one donated sample may create a renewable resource that can support multiple studies.
Why are fibroblasts needed if they can also be used to create iPSCs?
Fibroblasts are valuable both as research models themselves and as starting material for iPSC development. Researchers can study RNA splicing, cellular function, and other biological processes directly in fibroblasts. Comparing the original fibroblasts with iPSC-derived cells may also help investigators understand which findings are consistent across cell types.
Should someone undergo a lumbar puncture or skin biopsy solely to donate a sample?
Families should not arrange these procedures independently.
CSF and skin biopsies require collection by qualified medical professionals. COMBINEDBrain can coordinate with physicians when CSF or tissue is being obtained during medically necessary care, a scheduled procedure, or an appropriately approved research study. Whenever possible, a portion that would otherwise be discarded may be preserved for research.
RSU and COMBINEDBrain can provide collection instructions and shipping materials in advance.
Can existing CSF, fibroblasts, iPSCs, or other samples be transferred?
Possibly. Samples or cell lines already stored at a hospital, laboratory, or research institution may be eligible for institutional transfer if the existing consent, sample quality, documentation, and institutional requirements allow it.
Families should contact RSU before requesting a transfer so COMBINEDBrain can determine whether the material can be accepted and coordinate directly with the institution.
Why are samples from multiple individuals needed?
No single person can represent the entire ReNU community. Researchers need samples from people with different:
RNU4-2 variants
Ages and backgrounds
Medical histories
Clinical features
Levels of support needs
This helps researchers separate consistent biological effects of ReNU syndrome from normal differences among individuals. RSU may prioritize certain variants or sample types for a particular project, but all families are encouraged to express interest in future opportunities.
Why are samples from unaffected relatives valuable?
Samples from unaffected siblings or other adult relatives can provide important comparison data. Relatives may share genetic background and environmental influences with the person who has ReNU syndrome, making it easier to identify cellular differences most likely associated with the RNU4-2 variant.
Participation by an unaffected relative is voluntary. A relative’s decision generally does not prevent the individual with ReNU syndrome from participating unless a particular study requires matched samples.
Why is clinical information collected along with the sample?
A biospecimen is most valuable when researchers understand who it came from. With consent, information such as the participant’s RNU4-2 variant, age, diagnoses, medications, symptoms, seizures, developmental history, and other clinical features may be connected to the sample using a coded identifier.
COMBINEDBrain uses the secure Matrix platform for electronic consent and management of clinical information associated with the biorepository. Linking samples with clinical information may help researchers connect laboratory findings with the real-world experiences of people with ReNU syndrome.
How can samples be collected?
Depending on the opportunity and sample type, COMBINEDBrain may coordinate collection through:
A COMBINEDBrain Roadshow at a conference or community event
A home visit from a trained mobile phlebotomist
A clinic or physician’s office
A medically necessary procedure
Transfer from a hospital, laboratory, or research institution
Not every collection option is available in every location. RSU will help families determine what may be possible.
Who may use the samples?
Qualified researchers from academic institutions, nonprofit organizations, biotechnology companies, and pharmaceutical companies may request access.
Samples are not automatically released. Researchers must submit a formal request, and proposed use must align with participant consent and community priorities. Approved samples are distributed under appropriate research agreements.
Why might biotechnology or pharmaceutical companies receive samples?
Potential treatments rarely move forward through the work of one organization alone. Progress may require collaboration among families, advocacy organizations, clinicians, academic laboratories, biotechnology companies, and pharmaceutical companies.
Carefully governed access to high-quality RNU4-2 samples can help researchers validate discoveries, develop biomarkers, build disease models, and evaluate potential treatments.
How is privacy protected?
Participants complete electronic consent through Matrix before samples and clinical information are collected. The consent materials explain:
What samples and information will be collected
How they will be stored
How information may be connected to the sample
Who may request access
Whether future research and commercial research are permitted
What choices and withdrawal rights participants have
Researchers receive only the samples and information permitted under the approved request and participant consent.
Will donating provide a direct medical benefit?
A direct benefit cannot be promised. Biospecimen research is not medical care and may not personally benefit the donor.
However, donated samples can help build the scientific foundation needed to understand ReNU syndrome, develop meaningful laboratory models, identify possible biomarkers, and evaluate potential therapeutic approaches.
Can someone participate if they have donated samples elsewhere?
Possibly. Different studies may collect, process, or permit access to samples in different ways. Previous donations may not be available for new RNU4-2 research.
Families should tell RSU about any previous donations or existing cell lines. RSU and COMBINEDBrain can explore whether an existing sample can be transferred or whether an additional collection would provide a different research resource.
Can participants change their minds?
Participation is voluntary. Participants may request that remaining samples no longer be used, subject to the terms of the consent. Samples, data, or findings that have already been distributed or used in completed research may not be retrievable.
Choosing not to participate or deciding to withdraw will not affect a family’s relationship with RSU or access to community resources.
How could my family’s participation make a difference?
Researchers need access to appropriately collected samples that reflect the biology of people living with the condition.
A single donation may help researchers study disrupted RNA splicing, create renewable cell models, search for biomarkers, and test therapeutic ideas. When samples are collected consistently, connected with meaningful clinical information, and made available through responsible community oversight, each family’s contribution can become a lasting resource for the entire ReNU community.
How do we participate?
Begin by contacting ReNU Syndrome United. RSU will help determine which collection opportunities and sample types are currently available, then coordinate enrollment, consent, collection, and shipping with COMBINEDBrain.
Please contact united@renusyndrome.org before arranging a blood draw, procedure, sample transfer, or shipment.
