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Okaz et al. Rare Dis Orphan Drugs J. 2025;4:24 Rare Disease and
DOI: 10.20517/rdodj.2025.15
Orphan Drugs Journal

Perspective Open Access

From hype to hope: foundational requirements for
NF1 gene therapy success

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Elwy Okaz , Poornima Venkat 1 , Efrén Muñoz , Ivan Baines , Kalyan Vinnakota 1
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Gilbert Family Foundation, Detroit, MI 48226, USA.
2
Nick Gilbert Neurofibromatosis Research Institute, Detroit, MI 48226, USA.
Correspondence to: Dr. Kalyan Vinnakota and Dr. Elwy Okaz, Gilbert Family Foundation, 1074 Woodward Avenue, Detroit, MI
48226, USA. E-mail: KalyanVinnakota@gilbertfamilyfoundation.org; ElwyOkaz@gilbertfamilyfoundation.org
How to cite this article: Okaz E, Venkat P, Muñoz E, Baines I, Vinnakota K. From hype to hope: foundational requirements for NF1
gene therapy success. Rare Dis Orphan Drugs J. 2025;4:24. https://dx.doi.org/10.20517/rdodj.2025.15

Received: 10 Mar 2025 First Decision: 3 Jun 2025 Revised: 1 Jul 2025 Accepted: 6 Aug 2025 Published: 26 Aug 2025
Academic Editor: Daniel Scherman Copy Editor: Ping Zhang Production Editor: Ping Zhang

Abstract
Gene therapy for Neurofibromatosis type 1 (NF1), defined as a collection of approaches that restore the quantity
and function of neurofibromin, holds promise for treating various NF-associated clinical manifestations by
addressing the root cause of the condition. The Gilbert Family Foundation’s Gene Therapy Initiative (GTI) launched
one of the first focused research efforts to support a broad array of gene replacement, gene editing, and other
strategies aimed at upregulating neurofibromin levels to mitigate symptoms and advance therapies for NF1. Efforts
to discover and evaluate novel gene therapies to treat NF1 are hindered by foundational gaps in the field, the
absence of quantitative assays, and a lack of robust preclinical models with reliable functional readouts. This
perspective begins by shedding light on those key barriers that continue to hinder progress in NF1 gene therapy,
outlines some of the strategies being explored to overcome them and offers pointers to additional strategies that
merit further exploration. We then highlight several promising gene therapy strategies now in development.
Successfully addressing the challenges described earlier is critical to realizing the full potential of these emerging
and novel therapeutic approaches, setting the stage for effective and durable NF1 gene therapy interventions.

Keywords: Neurofibromatosis type 1, gene therapy, neurofibromin

INTRODUCTION
Neurofibromatosis type 1 (NF1) is a complex genetic disorder caused by mutations in the NF1 gene, which

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