Resource Overview

Initiatives

Initiatives are funder-organized programs, groups, consortia, cohorts, or awards, usually focused on a specific research area in neurofibromatosis.

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Studies

Studies are hypothesis-driven projects with the goal of uncovering new knowledge about neurofibromatosis type 1, type 2, or schwannomatosis.

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Files

Files are data collected from from human samples, animal models, and cell lines from a variety of assays.

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Datasets

Datasets are curated collections of files organized to facilitate data sharing.

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Papers

Papers are pre-prints and peer-reviewed articles produced by NF Data Portal studies.

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Tools

Tools include animal models, cell lines, genetic reagents, antibodies, and biobanks related to NF!

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New Studies

study

A Phase II Trial of ADI PEG20 in Combination with Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma

Angela Hirbe
This prospective single arm phase II study evaluated the efficacy and safety of combining ADI-PEG20 with gemcitabine and docetaxel in patients with advanced soft tissue sarcomas (STS), a heterogeneous group of mesenchymal malignancies with limited treatment options and poor outcomes in the metastatic setting. Building on preclinical evidence that most sarcomas are deficient in argininosuccinate synthetase...Show More
This prospective single arm phase II study evaluated the efficacy and safety of combining ADI-PEG20 with gemcitabine and docetaxel in patients with advanced soft tissue sarcomas (STS), a heterogeneous group of mesenchymal malignancies with limited treatment options and poor outcomes in the metastatic setting. Building on preclinical evidence that most sarcomas are deficient in argininosuccinate synthetase 1 (ASS1) and therefore dependent on extracellular arginine, the study investigated whether arginine deprivation with ADI PEG20 could enhance sensitivity to chemotherapy and overcome treatment resistance through modulation of metabolic pathways and upregulation of hENT1. The primary objective was to assess progression-free survival (PFS), while secondary objectives included evaluation of clinical benefit rate, efficacy, and safety of the triplet regimen across patients with advanced STS. Show Less
Study Status
Active
Data Status
Under Embargo
Disease Focus
Neurofibromatosis type 1
Manifestation
MPNST
Funding Agency
Other
Institutions
Washington University in St. Louis
On Synapse
study
Xiyuan Zhang
This project aims to understand and model disease progression in NF1 by studying the malignant transformation of nerve sheath tumors from plexiform neurofibroma (PN) through atypical neurofibroma (AN) to malignant peripheral nerve sheath tumor (MPNST). The central hypothesis is that malignant transformation is a preventable product of epigenetic re-wiring through a disrupted transcriptional program,...Show More
This project aims to understand and model disease progression in NF1 by studying the malignant transformation of nerve sheath tumors from plexiform neurofibroma (PN) through atypical neurofibroma (AN) to malignant peripheral nerve sheath tumor (MPNST). The central hypothesis is that malignant transformation is a preventable product of epigenetic re-wiring through a disrupted transcriptional program, formation of oncogene-harboring extrachromosomal DNA (ecDNA), and a malignant-prone tumor microenvironment. Aim 1 performs coupled single-nuclei RNA and ATAC sequencing on 30 NF1 nerve sheath tumors (10 PN, 10 AN, 10 MPNST) to determine cell-type specific gene regulatory networks governing malignant transformation. Aim 2 characterizes immune-modulating-gene-harboring ecDNA in MPNST using whole genome sequencing of 187 patient samples, validates findings via DNA FISH, and tests functional roles through engineered Schwann cell/immune cell co-culture and MPNST tumoroid models with anti-CXCL1/2 antibody treatment.Show Less
Study Status
Active
Data Status
Data Pending
Disease Focus
Neurofibromatosis type 1
Manifestation
MPNST,  Plexiform Neurofibroma,  Atypical Neurofibroma
Funding Agency
NTAP
Institutions
Rutgers State University of New Jersey, New Brunswick
On Synapse
Grant DOI

https://doi.org/10.54464/JHU-NTAP.1559821.pc.gr.242032

study
J. Elliott Robinson
Many children with NF1 experience cognitive symptoms, including attentional and executive function deficits, autistic features, sensory processing abnormalities, and difficulties with inhibitory control. In preliminary data, mice modeling NF1 (heterozygous Nf1 mice) showed increased reactivity to arousing visual stimuli in a looming stimulus assay, where Nf1 loss increased the probability and vigor...Show More
Many children with NF1 experience cognitive symptoms, including attentional and executive function deficits, autistic features, sensory processing abnormalities, and difficulties with inhibitory control. In preliminary data, mice modeling NF1 (heterozygous Nf1 mice) showed increased reactivity to arousing visual stimuli in a looming stimulus assay, where Nf1 loss increased the probability and vigor of escape evoked by looming discs that mimic predator approach from above. This phenotype was genocopied by mice with a gain-of-function mutation in ERK2, suggesting it is caused by enhanced Ras/MAPK signaling. While activated MAPK expression in the midbrain, cerebellum, and forebrain GABAergic neurons did not increase threat reactivity, mice with MAPK activation in the cerebral cortex had higher escape velocity, shorter latency to escape, and impaired ability to habituate to repeated threat stimuli, consistent with a deficit in inhibitory control. Histological analysis revealed macrocephaly and abnormalities in large fiber tracts such as the internal capsule, raising the possibility that cortical projection defects could cause visual hypersensitivity in NF1 model mice by altering top-down regulation of subcortical sensory processing centers. This project hypothesizes that Nf1 loss in the developing cerebral cortex disrupts deep layer glutamatergic neuronal innervation of subcortical sensory processing centers, enhancing threat reactivity by impairing inhibitory control. Aim 1: Using conditional genetic and viral vector-based knockout animals, identify cell types and cortical sites in which Nf1 loss enhances the behavioral response to looming visual threats and produces ADHD-like phenotypes such as impulsivity in the cliff avoidance assay and hyperactivity during open field testing. Aim 2: Using advanced methods to reconstruct cortical projections brain-wide, determine the effects of cortical Nf1 loss on structural connectivity in NF1 mouse models.Show Less
Study Status
Active
Data Status
Data Pending
Disease Focus
Neurofibromatosis type 1
Manifestation
Cognition
Funding Agency
NTAP
Institutions
Cincinnati Children's Hospital Medical Center
On Synapse
Grant DOI

https://doi.org/10.54464/JHU-NTAP.1591512.pc.gr.243868

Data Contributor Spotlight

Jaishri Blakeley

JOB@synapse.org

David Gutmann

Donald O. Schnuck Family Professor / Washington University

Gutmann@synapse.org

Bio

Dr. Gutmann received his MD and PhD degrees from the University of Michigan prior to residency training in Neurology at the University of Pennsylvania. Following a post-doctoral research fellowship with Dr. Francis Collins where he identified and characterized the NF1 protein (neurofibromin), Dr. Gutmann joined the faculty in Neurology at the Washington University School of Medicine in late 1993. His research laboratory employs NF1 as a model genetic system to understand normal growth and differentiation in the normal brain. In this fashion, they aim to characterize the genetic, cellular, and molecular factors that contribute to the development of nervous system tumors (gliomas and neurofibromas) and cognitive problems (learning and attention deficits). Defining these contributing factors represents the first step toward establishing new treatments for children and adults with NF1. Moreover, NF1 provides unique opportunities to unravel the complexities of related medical problems in the general population, including adult and childhood brain tumors, breast cancer, and autism. In addition, Dr. Gutmann directs the Washington University Neurofibromatosis Center (http://nfcenter.wustl.edu), one of the world's largest basic and clinical science research programs focused on accelerating the pace of scientific discovery and its application to individuals affected with NF. Our mission is to provide exceptional care through groundbreaking research. Specialties: Clinical care of children and adults withe neurofibromatosis Brain tumor and neurofibromatosis research

More Info

https://nfcenter.wustl.edu

Industry

Higher Education

Location

Greater St. Louis Area

Robert Allaway

Director, Rare Disease / Sage Bionetworks

allawayr@synapse.org

Bio

Robert Allaway leads the rare disease work at Sage Bionetworks. The majority of his research involves applying computational methods to the study of neurofibromatosis type 1, type 2, and schwannomatosis (NF). Most recently, his work has focused on identifying challenges and opportunities in genomic analysis of rare tumor data from NF, as well as designing and implementing bioinformatic analyses for data derived from NF tumor models. In addition to his research role, he also leads other projects with the broad goal of promoting open science approaches in biomedical research and algorithm development for biomedical applications.

Location

Seattle, WA

Our Partners

ORGANIZATION

Children's Tumor Foundation (CTF)

Founded in 1978, the Children's Tumor Foundation (CTF) began as the first grassroots organization solely dedicated to finding treatments for neurofibromatosis (NF). Today, CTF is a widely recognized national nonprofit foundation, a leading force in the fight to end NF, and a model for other innovative research endeavors. CTF has partnered with Sage Bionetworks to create a pan-NF data portal available for NF researchers and other stakeholders. The portal contains molecular and clinical data coming from the many projects that the Foundation is managing. In particular, the Synodos consortia projects will use platforms built by Sage Bionetworks to execute their data analysis and integration, releasing their datasets in a timely fashion. The Synodos projects work with a 12-month embargo on data release, allowing their participants to share results in real-time within an exclusive space, and then releasing them after the confidentiality period. Many other projects that the Foundation is managing and sponsoring will also use this platform as a resource for making data available for the research community. The data being generated by CTF-funded projects include drug screening datasets, genomic characterization of model systems, multiplexed analysis, and several other publicly available datasets.
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ORGANIZATION
The Neurofibromatosis Therapeutic Acceleration Program (NTAP) is dedicated to finding new treatments for individuals with plexiform neurofibromas and cutaneous neurofibromas. NTAP uses a collaborative approach that brings together patients, clinicians, researchers, industry, and government to determine where resources are most effectively used to discover new treatments. NTAP's mission is to: 1) focus on therapeutics, 2) foster collaboration, 3) share results in an open and timely manner, and 4) streamline the research process. Exceptional partners are recruited to make these plans a reality, through both targeted programs and investigator-initiated proposals. NTAP invests in all areas of therapeutic discovery for plexiform and cutaneous neurofibromas, with the ever-present final goal of an effective therapy for patients.
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ORGANIZATION
The Gilbert Family Foundation is a private nonprofit foundation founded by philanthropists Dan and Jennifer Gilbert to address their two priorities and passions: accelerating a cure for neurofibromatosis type 1 (NF1) and transforming the city of Detroit, Michigan. The Foundation has embarked on two bold, high risk/high reward NF1 research initiatives: (1) the Gene Therapy Initiative (GTI), to develop curative therapies that address the underlying genetic abnormalities in NF1 patients, and (2) the Vision Restoration Initiative (VRI), inspired by their son’s loss of vision from NF1 and with a goal of advancing vision restoration therapies. In December 2018, GTI announced the award of more than $12 million dollars to eight multi-disciplinary research teams to develop gene-targeting therapeutic strategies or in vivo gene delivery systems with areas of interest including gene replacement, gene editing, RNA editing, exon skipping, nonsense mutation suppression, and gene delivery systems. In April 2019, VRI launched awarding almost $11M over 3 years to a consortium of distinguished ophthalmology and NF1 expert investigators, collaborating as part of a scientific “Dream Team”. This initiative is focused on developing three types of therapeutic products to restore vision in NF1 patients who have lost their sight due to optic pathway glioma: endogenous cell replacement, exogenous cell replacement, and neuro-enhancement.
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ORGANIZATION
The Developmental and Hyperactive RAS Tumor SPORE (DHART SPORE) is an NCI project focused on identifying new treatment for tumors associated with NF1 mutations including plexiform neurofibromas, malignant peripheral nerve sheath tumors, juvenile myelomonocytic leukemia, and radiation and chemotherapy-induced malignant neoplasms in NF1 patients.
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ORGANIZATION
The NFRP was established in fiscal year 1996 (FY96), when the efforts of neurofibromatosis (NF) advocates led to a Congressional appropriation of $8 million (M). Since that time, $332.85M has been appropriated to the program, including $15M in FY18. Over its 20-year history, the NFRP has invested in key initiatives to support the development of critical resources, sponsor multidisciplinary collaborations, bring talented investigators into the field, and promote the translation of promising ideas into the clinic. Through the recommendations of the NFRP Programmatic Panel, the NFRP has developed the following vision: decrease the clinical impact of neurofibromatosis, and mission: promote research directed toward the understanding, diagnosis, and treatment of NF1, NF2 and schwannomatosis to enhance the quality of life for persons with these disorders that impact Service members, Veterans, and the general public.
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ORGANIZATION
The mission of the NF1 Research Initiative (NFRI) is to advance pre-clinical research towards effective treatment of neurofibromatosis-related tumors. The initial focus of the NFRI will be on malignant peripheral nerve sheath tumors (MPNSTs), for which there is currently no effective medical treatment.
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What's New

funding

April 2022

N-TAP Announces an RFA for Biology and Therapeutic Development for NF1 Associated Cutaneous Neurofibromas

The Neurofibromatosis Therapeutic Acceleration Program (NTAP) (www.n-tap.org) is a philanthropic research entity based at Johns Hopkins University School of Medicine dedicated to the discovery of therapeutics for the peripheral nerve tumors that afflict people with Neurofibromatosis Type 1 (NF1). They have announced a Request for Applications for up to 15 funded projects. Funded projects …
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March 2022

Researcher Spotlight: Astrid Behnert, M.D.

What is your name, title and institutional affiliation? Astrid Behnert Department of Pediatrics, Benioff Children’s Hospital University of California, San Francisco What is your role, ie what do you do? I’m a clinician-scientist with a research focus on cancer predisposition and childhood leukemia. Please share your favorite discovery from your NF research. What makes this …
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February 2022

Researcher Spotlight: R. Taylor Sundby, MD

What is your name, title and institutional affiliation? R. Taylor Sundby, MD Advanced Clinical Fellow Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health What is your role, ie what do you do? After completing my pediatric hematology-oncology fellowship, I was given the opportunity to continue my training at the NIH as an advanced …
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Top 10 Studies (Last 30 Days)

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Genetic Studies of Neurofibromatosis

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