FDA clears IND for investigational SUMF1 gene therapy in multiple sulfatase deficiency

The FDA has cleared an Investigational New Drug (IND) application for a gene therapy intended to treat multiple sulfatase deficiency (MSD), an ultra-rare pediatric lysosomal storage disorder, clearing the way for a planned first-in-human study of safety and tolerability.¹ The application is sponsored by the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health, and was developed through the Accelerating Medicines Partnership Bespoke Gene Therapy Consortium (AMP BGTC), a public-private partnership among the NIH, FDA, biopharmaceutical companies, and nonprofit organizations.¹

In an earlier statement on the underlying preclinical program, Maximiliano Presa, PhD, study director at The Jackson Laboratory, said the research team’s efforts were focused on the critical next steps needed to bring gene therapy to children affected by MSD.²

Regulatory pathway and trial design for the MSD gene therapy program

MSD entered the BGTC after much of its preclinical work was already complete, and the consortium subsequently supported manufacturing of the clinical-grade vector product and collaborative development of the clinical protocol and IND submission.¹ Input came from BGTC manufacturing, regulatory, and clinical subject-matter experts, along with a protocol review committee that included patient advocates and a parent of a child with MSD.¹ The planned study is a first-in-human trial designed primarily to assess safety and tolerability, with exploration of potential therapeutic effects as a secondary goal; specific endpoints, dosing, and enrollment criteria have not been publicly detailed.¹ Principal investigators Laura Adang, MD, PhD, and Rebecca Ahrens-Nicklas, MD, PhD, of Children’s Hospital of Philadelphia (CHOP), will lead the clinical study.¹

Disease burden and unmet need in multiple sulfatase deficiency

MSD is caused by loss-of-function mutations in the SUMF1 gene, which encodes an enzyme needed to activate the full family of sulfatase enzymes; without it, sulfated substrates accumulate in cells, driving progressive neurologic and somatic decline.³ The disorder affects growth and development and is life-limiting, with an average life expectancy of approximately 13 years.¹ No disease-modifying treatments currently exist, and management is limited to supportive care aimed at symptoms and quality of life.¹

Vector design and preclinical rationale

The therapy uses an AAV9 vector to deliver a functional copy of SUMF1, restoring production of the enzyme that activates sulfatases throughout the body.⁴ In preclinical studies conducted at The Jackson Laboratory and UT Southwestern Medical Center, delivery of the vector to Sumf1 knockout mice extended survival, with neonatal treatment supporting survival out to one year and later administration via the cerebrospinal fluid at day 7 of life still improving outcomes.⁴ The gene therapy itself was developed by Steven Gray, PhD, and Rachel Bailey, PhD, of UT Southwestern, with pivotal preclinical testing led by Cathleen Lutz, PhD, and Dr. Presa at The Jackson Laboratory.¹

Interpreting the milestone and what remains uncertain

An IND clearance is a regulatory milestone that permits human testing to begin; it is not itself evidence of safety or efficacy in patients. The supporting preclinical data, generated in a knockout mouse model with a short natural lifespan, showed extended survival and symptom mitigation, but rodent models of ultra-rare metabolic disease do not always predict human dosing, immunogenicity, or long-term safety.⁴ Because AAV9 gene therapies carry known risks, including immune responses and, in some programs, hepatotoxicity or neurotoxicity, the first-in-human study’s core objective is appropriately safety and tolerability rather than efficacy.¹

Limitations and next steps

MSD’s ultra-rare incidence limits the eventual trial population and the statistical power of early efficacy signals. No public information yet describes planned dosing, route of administration for the human study, or a defined timeline for enrollment. The BGTC has developed a shared regulatory playbook intended to standardize development for other bespoke gene therapies, but whether this program’s pathway can be generalized to other ultra-rare diseases remains to be demonstrated as the trial proceeds.¹

References

1. Foundation for the National Institutes of Health. AMP BGTC announces FDA clearance of Investigational New Drug application for gene therapy targeting multiple sulfatase deficiency. July 6, 2026. Accessed July 6, 2026. https://fnih.org/news/bgtc-msd-ind-clearance/

2. The Jackson Laboratory. Promising data supports a gene therapy approach for ultra-rare genetic disorder, multiple sulfatase deficiency. February 2022. Accessed July 6, 2026. https://www.jax.org/news-and-insights/2022/february/promising-data-supports-gene-therapy-for-msd

3. MedlinePlus Genetics. Multiple sulfatase deficiency. US National Library of Medicine. Accessed July 6, 2026. https://medlineplus.gov/genetics/condition/multiple-sulfatase-deficiency/

4. Presa M, Bailey RM, Ray S, et al. Preclinical use of a clinically-relevant scAAV9/SUMF1 vector for the treatment of multiple sulfatase deficiency. Commun Med. 2025;5. doi:10.1038/s43856-025-00734-9