$300,000 committed to advancing therapeutic development for childhood-onset SPG4 

The Lilly and Blair Foundation have announced the recipients of its inaugural Strategic Research Grant Program, committing $300,000 to advance therapeutic development for childhood-onset SPG4. 

This funding cycle marks a significant milestone in the Foundation’s growing research portfolio. Through a competitive application process, the Foundation received nine proposals from investigators representing leading institutions across the United States, Canada, and Europe. Collectively, these proposals reflected the growing momentum within the childhood-onset SPG4 research community and the expanding range of approaches being pursued to accelerate treatment development. 

Applications included gene therapy, gene editing, antisense oligonucleotides (ASOs), drug repurposing, biomarker development, disease modeling, and therapeutic target discovery. 

Proposals underwent a rigorous scientific review by the Foundation’s Grant Review Board and were evaluated based on scientific merit, feasibility, translational potential, strategic alignment, and their potential to rapidly advance therapies for children living with SPG4. 

Following review, the Foundation selected two programs for funding.

“The breadth and quality of the applications we received was exceptional. The two funded projects stood out not only for their scientific merit, but also for their translational potential. They will support the development of a mutation-agnostic gene therapy and an innovative drug discovery and repurposing effort that offer complementary paths to new treatments for SPG4.”

— Matthew Elrick, MD, PhD, Assistant Professor of Neurology, Kennedy Krieger Institute and Chair of the Grant Review Board for The Lilly and Blair Foundation

Gene therapy development and translation

The Foundation has awarded a two-year, $150,000 grant ($75,000 per year) to Miguel Sena-Esteves, PhD, and colleagues at UMass Chan Medical School. 

This project will advance development of a mutation-agnostic gene therapy strategy designed to address the underlying biology of SPG4 across multiple disease-causing variants. Funding will support optimisation and preclinical evaluation of next-generation AAV-SPAST gene therapy constructs, generating critical data related to target engagement, biodistribution, and safety while helping identify lead candidates for future translational development. By supporting this work, the Foundation aims to accelerate progress toward a broadly applicable therapeutic strategy for children living with SPG4.

“This funding lets us push a mutation-agnostic gene therapy strategy through the critical preclinical work needed to move toward the clinic. Because this approach is designed to work across multiple SPG4 causing variants rather than targeting just one, it has the potential to reach a much broader group of children than a mutation-specific therapy could. We’re grateful to the Lilly and Blair Foundation for recognising that potential and helping us generate the data needed to identify our best candidates going forward.”

— Miguel Sena-Esteves, PhD, Associate Professor of Genetic & Cellular Medicine and Neurology and Director of the Translational Institute for Molecular Therapeutics (TiMT), UMass Chan Medical School

Therapeutic discovery and drug repurposing

The Foundation has awarded a two-year, $150,000 grant ($75,000 per year) to Liang Oscar Qiang, MD, PhD, and colleagues at Drexel University College of Medicine. 

This project will utilise patient-derived disease models to identify and evaluate potential FDA-approved therapeutic candidates while expanding understanding of the biological mechanisms underlying SPG4. By combining disease modeling with therapeutic screening approaches, the program seeks to accelerate the identification of interventions that may be advanced into future preclinical and translational studies. This investment reflects the Foundation’s commitment to pursuing multiple therapeutic pathways while strengthening the pipeline of potential treatment opportunities for childhood-onset SPG4.

“Patient-derived brain organoid models allow us to study SPG4 biology in human neural tissue that is directly relevant to the children affected by this disease, rather than relying solely on animal models or simplified cell cultures. This grant allows us to expand that work and more rigorously test potential therapeutic candidates, including high-throughput screening of existing drugs guided by machine learning and AI-based analysis. We are grateful for the Foundation’s support in helping us move this research forward with the urgency this community deserves.”

— Liang Oscar Qiang, MD, PhD, Associate Professor, Neurobiology & Anatomy, Drexel University College of Medicine

Building the SPG4 therapeutic pipeline

The Foundation extends its sincere appreciation to all investigators who submitted proposals and to the scientific reviewers who contributed their expertise throughout the evaluation process. While only two programs could be selected for funding this cycle, the breadth of applications received reflects the growing momentum behind childhood-onset SPG4 research worldwide and the Foundation remains committed to investing in research, scientific infrastructure, and collaborative partnerships that accelerate the path toward meaningful treatments for children living with SPG4.

About the Lilly and Blair Foundation

The Lilly and Blair Foundation is a 501(c)(3) nonprofit organisation focused on accelerating treatments for childhood-onset SPG4, a rare and progressive neurodegenerative disorder. Founded in 2023, the Foundation serves as a catalyst for research, collaboration, and therapeutic development by funding high-impact science, convening experts from around the world, and building the partnerships needed to move promising discoveries toward patients. The Foundation’s growing research portfolio spans gene therapy, therapeutic discovery, disease modeling, and clinical readiness, with investments supporting programs at leading institutions including Boston Children’s Hospital, UMass Chan Medical School, Drexel University, and the University of Wisconsin. Through its annual Scientific Symposium and global network of families, clinicians, and researchers, the Foundation is helping create a coordinated path toward treatments for children living with SPG4. Learn more at lillyandblair.org.

---