This report provides a comprehensive analysis of the Children's Tumor Foundation's (CTF) approach to addressing NF2-related schwannomatosis (NF2-SWN), a rare genetic condition affecting approximately 1 in 25,000 people worldwide. The analysis synthesizes information from CTF's patient education resources and research progress updates, validated by peer-reviewed literature and authoritative medical sources.
The findings reveal CTF's multifaceted strategy, combining patient education, collaborative research initiatives, innovative clinical trial methodologies, and promising treatment developments. Recent breakthroughs, particularly with the drug brigatinib, demonstrate significant progress in the search for effective treatments for this challenging condition.
NF2-SWN is characterized by the development of bilateral vestibular schwannomas (benign tumors on the eighth cranial nerve), leading to hearing loss and balance problems. Patients may also develop other brain and spinal tumors and experience a range of symptoms affecting multiple body systems.
The condition was formerly called neurofibromatosis type 2 (NF2) but was reclassified in May 2022 as "NF2-related schwannomatosis," positioning it as a type of schwannomatosis rather than a separate condition12. This terminology evolution reflects advancing understanding of the genetic relationships between NF conditions.
The most significant recent advancement is the development of brigatinib for NF2-SWN. The INTUITT-NF2 platform trial found promising results, published in the New England Journal of Medicine in 2024, showing tumor shrinkage (10% of growing tumors and 23% of all tumors), improved hearing, and reduced pain in some patients34.
This research was directly attributed to CTF's Synodos initiative and represents a major breakthrough in potential treatment options for NF2-SWN patients5.
Selumetinib (Koselugo), which received FDA approval in 2020 for NF1, is currently in Phase 2 clinical trials for NF2-SWN tumors6. While efficacy data specifically for NF2-SWN is still developing, a 2024 Nature Medicine publication demonstrated significant efficacy in NF1 patients, with an objective response rate of 63.6%7.
The INTUITT-NF2 trial evaluates multiple treatments simultaneously, increasing efficiency in the search for effective therapies. This approach allows for "the simultaneous study of the various tumor types, rather than waiting for studies on one tumor type alone, thereby accelerating the information gathering and results analysis"89.
CTF is also partnering with EU-PEARL in Europe to develop similar platform trial protocols that can be implemented globally.
CTF is funding the University of Plymouth to develop a humanized preclinical testing meningioma model for NF2-SWN brain tumor therapies, addressing a critical gap in the research pipeline.
CTF has implemented several collaborative research models:
- NF2 Accelerator Initiative: A $2.3 million investment launched in 2019 to expand the clinical drug pipeline
- Synodos for NF2: A "dream team" of multidisciplinary investigators from 12 world-class labs at 8 institutions, established in 2014 with $3 million in funding10
- NF Data Portal: A centralized repository for shared research data
- NF Preclinical Initiative: Completed 116 preclinical trials in 8 years for $11 million
CTF participates in the Year of Open Science collaboration with NASA and the Center for Open Science, emphasizing data sharing to accelerate discoveries.
CTF employs a multi-faceted strategy to address NF2-SWN:
CTF brings together academic researchers, pharmaceutical companies, healthcare providers, and patients to create a collaborative ecosystem. The Synodos initiative exemplifies this approach, with published research in PLOS ONE demonstrating significant achievements:
- Creating a pipeline of validated tools for drug discovery
- Gaining insights into disease mechanisms
- Validating pathways and targets
- Building an openly accessible database for community sharing10
The organization provides multiple funding mechanisms including Young Investigators Awards, Drug Discovery Initiative, Clinical Research Awards, and Gene Therapy awards, creating multiple "shots on goal" for discovering effective treatments.
The tripling of clinical trials for NF over the past decade demonstrates CTF's success in moving potential treatments from lab to clinic. The INTUITT-NF2 platform trial specifically exemplifies their innovative approach to accelerating treatment development.
Patients are integral to the research process through the NF Registry, which collects data on symptoms and experiences while connecting patients to clinical trials. CTF also emphasizes that patients are "not their diagnosis" and encourages community support and involvement in research.
CTF provides educational materials, specialist directories, and community support to help patients navigate their diagnosis and treatment. These resources are designed to empower patients and connect them with appropriate specialized care.
Several quantifiable achievements highlight CTF's progress:
- 1,931 drugs screened in Synodos for NF2
- 8 team science initiatives leading to treatments like selumetinib for NF1 and brigatinib for NF2-SWN
- 10 pharma/biotech companies drawn toward NF research
- 116 preclinical trials completed in 8 years through the NF Preclinical Initiative
- Tripling of clinical trials compared to a decade ago
The NF2-SWN landscape has evolved significantly in recent years, with promising treatments in clinical trials, a growing research infrastructure, and increasing pharmaceutical industry engagement. The brigatinib results published in 2024 represent a significant milestone in the search for effective treatments.
CTF's emphasis on collaboration, data sharing, and patient involvement creates a robust ecosystem to accelerate treatment development for this rare condition. Their comprehensive approach—spanning from patient education to clinical trials—demonstrates a commitment to improving outcomes for individuals affected by NF2-SWN.
While there is currently no cure for NF2-SWN, the research landscape shows substantial progress toward effective treatments, with multiple promising approaches in the pipeline.
Footnotes
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National Organization for Rare Disorders (NORD). "NF2-Related Schwannomatosis - Symptoms, Causes, Treatment." Retrieved from https://rarediseases.org/rare-diseases/neurofibromatosis-2/ ↩
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GeneReviews, NCBI Bookshelf. "NF2-Related Schwannomatosis." Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK1201/ ↩
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New England Journal of Medicine. (2024). "Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors." DOI: 10.1056/NEJMoa2400985 ↩
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European Society for Medical Oncology (ESMO). (2024). "Treatment with Brigatinib Results in Radiographic Responses and Clinical Benefit in a Heavily Pretreated Cohort of Patients with NF2-Related Schwannomatosis." Retrieved from https://www.esmo.org/oncology-news/treatment-with-brigatinib-results-in-radiographic-responses-and-clinical-benefit-in-a-heavily-pretreated-cohort-of-patients-with-nf2-related-schwannomatosis ↩
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Children's Tumor Foundation. (2024). "Brigatinib Shows Promise for NF2-SWN: A Direct Result of CTF's Synodos Initiative." Retrieved from https://www.ctf.org/news/brigatinib-shows-promise-for-nf2-swn-result-ctf-synodos/ ↩
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Children's Tumor Foundation. "Progress in NF2-SWN." Retrieved from https://www.ctf.org/progress-in-nf2swn/ ↩
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Nature Medicine. (2024). "Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial." Retrieved from https://www.nature.com/articles/s41591-024-03361-4 ↩
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Children's Tumor Foundation. "Children's Tumor Foundation Announces New NF2 Clinical Trial: INTUITT for NF2." Retrieved from https://www.ctf.org/news/new-nf2-clinical-trial-intuitt-for-nf2/ ↩
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Children's Tumor Foundation. "Bringing Brigatinib to Neurofibromatosis Type-2 Patients: From Promising Potential to Platform Clinical Trial." Retrieved from https://www.ctf.org/news/clinical-trial-intuitt-for-nf2-press-release/ ↩
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EurekAlert. (2018). "Synodos for NF2 Consortium publishes key results of its work." Retrieved from https://www.eurekalert.org/news-releases/579034 ↩ ↩2