Ex vivo autologous stem cell gene therapy for Multiple Sulfatase Deficiency

Multiple Sulfatase Deficiency (MSD) is an inherited lysosomal storage disorder (LSD) that predominately involves the brain, bones, and skin. The disease is due to mutations in SUMF1, a gene that provides the instructions for making an important enzyme called formylglycine generating enzyme (FGE). The FGE enzyme activates all the sulfatases in cells throughout the body. Sulfatases break down sulfate-containing molecules. Without functional sulfatases, molecules build up in the lysosomes leading to cellular dysfunction. 

Unfortunately, there are no approved therapies for MSD. Patients experience progressive neurologic and physical decline, and ultimately die at a median age of 13 years. Recently, advances have been made for related single sulfatase disorders, including combined gene therapy and hematopoietic stem cell transplant (HSCT) therapy. In this approach, a patient’s bone marrow cells are removed, and a deficient gene is replaced using a lentiviral vector. The patient then undergoes a stem cell transplant. The corrected bone marrow-derived cells provide the missing protein to the patient, correcting the biochemical deficit. This is now an EMA-approved therapy for Metachromatic Leukodystrophy, a disorder closely related to MSD.

In this work, we aim to develop this ex vivo gene therapy with HSCT for MSD. Our preliminary data demonstrate that our lentiviral vector can correct the gene defect and improve markers of disease in MSD patient cells. We will expand upon our investigations in cells and evaluate the efficacy of this approach in a mouse model of MSD. Ultimately, we aim to transition this treatment into clinical trials in order to improve outcomes for patients with this devastating, untreatable disorder.

Award Date
01 July 2022
Award Value
Principal Investigator
Dr Rebecca Ahrens-Nicklas
Host Institution
The Children's Hospital of Philadelphia
HRCI-HRB Joint Funding Scheme