Resources

At The Lilly and Blair Foundation, we believe informed families are powerful allies in the fight against de novo SPG4. This page offers trusted resources to help you understand the disease, connect with the community, and participate in research. Whether you’re newly diagnosed or seeking the latest developments, these tools are here to support you every step of the way.

Research Participation

Explore opportunities to contribute to SPG4 research. Each of the programs below plays a unique role in advancing understanding, diagnosis, and treatment for Hereditary Spastic Paraplegia. Learn more and enroll on Research page.

Pediatric Natural History Study (SP-CERN)
Run by Boston Children’s Hospital, this study collects clinical data and biosamples from children and young adults (≤30 years) with early-onset SPG4. It helps identify trial-ready endpoints and supports the path toward therapies.

SP-CERN Registry and Biorepository
Through SP-CERN, patients of all ages can contribute to a centralized registry, biobank, and genomic archive—helping increase visibility of early-onset SPG4 and support research across multiple institutions.

SPG4 Biobank (Coriell Institute)
Families can donate blood or skin samples to Coriell’s NIGMS Repository, a global resource for SPG4 research. Samples have already helped create SPG4 brain organoids used to study disease and test treatments.

HSPseq Genomic Sequencing Initiative
Led by Boston Children’s Hospital, this study uses genomic sequencing to uncover genetic causes of childhood-onset spasticity. Open to children and young adults (1 month–30 years) with progressive spasticity.

Learn more on our Research page

Recent Papers

  • Modeling spastic paraplegia 4 with corticospinal motor neuron-enriched cortical organoids reveals genotype-phenotype and HDAC6-targetable pathology

    Published in Cell Reports, this study used human stem cell-derived cortical organoids and SPG4 mouse models to identify HDAC6 hyperactivation as a disease-relevant and pharmacologically targetable mechanism in SPG4. Researchers demonstrated that inhibiting HDAC6 restored microtubule stability, reduced axonal degeneration, and improved gait and corticospinal tract pathology in preclinical models, advancing understanding of SPG4 disease biology and therapeutic development.

    Read the Paper

  • Intracerebroventricular SPAST-AAV9 gene therapy prevents manifestation of symptoms in a mouse model of SPG4 hereditary spastic paraplegia

    Published in Molecular Therapy, this preclinical study demonstrated that a dual-function AAV9 gene therapy prevented corticospinal tract degeneration and gait abnormalities in a mouse model of SPG4 hereditary spastic paraplegia. By silencing mutant SPAST and replacing it with healthy spastin, researchers showed successful prevention of disease progression, providing important proof-of-concept for gene therapy approaches in SPG4.

    Read the Paper

  • Genotype–structure–phenotype correlations define divergent natural history in early-onset spastic paraplegia type 4

    Published in Brain, this landmark international study analyzed 206 individuals with genetically confirmed SPG4 and identified two distinct disease trajectories: a severe, rapidly progressive subgroup often associated with de novo missense variants, and a more moderate subgroup with slower progression. Researchers demonstrated that specific genetic variants can help predict disease severity, developmental outcomes, mobility loss, and progression over time, providing the most detailed natural history data for early-onset SPG4 to date. The study also established a biologically informed framework for patient stratification that could improve clinical trial design, anticipatory care, and future treatment development for SPG4.

    Read the Paper

Community Insights

Patient engagement is essential to advancing SPG4 research and care. The following community-led efforts—created by parents and patients—offer valuable insights, shared experiences, and data that inform the scientific landscape while empowering families.

  • Understanding SPG4: A Parent’s Guide to Early-Onset De Novo SPG4 (p.Arg499His Mutation)

    Created by a parent in collaboration with The Lilly and Blair Foundation, this guide offers a deeply personal, scientifically grounded overview of what it means to live with the rare p.Arg499His mutation in the SPAST gene. It walks families through:
    • What de novo SPG4 is and how it differs from inherited forms
    • What the p.Arg499His mutation does at the cellular level
    • Why symptoms may be more severe in early-onset, de novo cases
    • Frequently asked questions about genetics, severity, recurrence risk, and care
    • Key researchers, clinical research landscape, and family-friendly explanations of complex topics

    This is the most mutation-specific, family-centered SPG4 resource available—and it was written to empower and inform parents navigating a new diagnosis.

    View the Guide

  • Childhood-Onset HSP Report

    This report highlights the growing momentum behind research and therapeutic development for childhood-onset SPG4 and related forms of HSP. Inside, readers will find updates on gene therapy, genome and base editing, biomarker discovery, patient-derived disease models, and global research collaborations, along with reflections from families and leaders helping drive this work forward. The publication also showcases how coordinated efforts between families, clinicians, researchers, and advocacy organizations are accelerating progress toward meaningful treatments and improved clinical readiness for children impacted by childhood-onset HSP.

    View the 2026 Report

How Can You Help?

  • DONATE

    Make a meaningful impact by contributing directly to our campaign! Don’t forget to check if your employer offers matching donations—your gift could go even further.

    Consider setting up a Facebook fundraiser for your birthday, the holiday season, or simply to spread kindness.

    If you’re active on Instagram, it’s easy to make a difference! Create a post, select "Add Fundraiser," choose The Lilly and Blair Foundation, fill in the details, and then share it with your followers.

    Every contribution counts and 100% of donations will go to research that supports finding a treatment or cure for childhood-onset, de novo SPG4.

  • SHARE

    Stay connected with us on social media @lillyandblair. Share our mission and stories with your friends and family to help raise awareness.

    Download our informative one-pager and distribute it to your loved ones and community.

    Together, we can spread the word and inspire others to join our cause.

  • PARTICIPATE

    Get involved by joining us at our upcoming events or consider hosting your own. Your participation makes a difference.

    4th Annual Golf Tournament and Dinner
    Friday, May 26, 2026 | Clifton, VA

    5K Run, Roll, and Stroll (+Play!)
    Sunday, September 13 | McLean, VA or virtual

    2nd Annual Winter Benefit
    Friday, November 13 | Leesburg, VA

What happens next depends on how quickly we move.

Your support accelerates progress toward real treatments for children with SPG4.

Donate Now