Objective: SBT101 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy candidate delivering a functional copy of the human ABCD1 gene that is in development as a treatment for adrenomyeloneuropathy (AMN). Here we evaluated the dose dependent effect of SBT101 on the behavior and function of Abcd1/Abcd2 double knock-out mice (DKO; Abcd1-/y/Abcd2-/-), a mouse model of AMN.
Background: AMN is an inherited neurodegenerative disease caused by mutations in the ABCD1 gene which encodes a peroxisomal transporter for very long-chain fatty acids (VLCFA). In the absence of functional ABCD1, VLCFA accumulates within affected cells leading to oxidative stress at the cellular level and a progressive axonopathy in the spinal cord. Symptoms of AMN typically occur first in adulthood and affect virtually all males and >80% of females with the mutation. Patients with AMN experience slow, progressive spastic paraparesis leading to loss of mobility, incontinence, and debilitating pain; there is currently no treatment for AMN.
Method: DKO male mice aged 7–8 months received a single lumbar intrathecal (IT) bolus of SBT101 (3.3E10 or 3.3E11 vector genomes/animal [vg/an]), and control wild-type (WT) and DKO male mice received empty vector (AAV9-Null; 1.5E11 vg/an). Animal grip strength was evaluated at 15 and 18 months of age, followed by post-mortem analysis of VLCFA levels in lumbar spinal cord.
Results: IT administration of SBT101 and AAV9-Null were well tolerated by DKO and WT mice. Four-paw grip strength was significantly increased at 15 months of age and maintained at 18 months of age in DKO mice receiving either dose of SBT101 versus AAV9-Null. At 10 months post treatment, SBT101 led to dose-dependent reductions in VLCFA levels of 5% (3.3E10 vg/an) and 16% (3.3E11 vg/an) in the lumbar spinal cords of DKO mice compared with AAV9-Null treatment.
Conclusion: IT delivery of SBT101 in DKO mice demonstrated dose-dependent improvement of four-paw grip strength and VLCFA levels. These data support further preclinical development of SBT101 as a potential treatment for AMN.
To cite this abstract in AMA style:
A. Pujol, A. Bosch, I. Dijkstra, S. Kemp, Y. Jaspers, S. Verdés, S. Fourcade, C. Guilera, M. Leal-Julià, A. Onieva, V. Vasireddy, SW. Clark, D. Anderson, K. Kozarsky. An AAV9 encoding human ABCD1 (SBT101) shows functional improvement following spinal cord delivery in a rodent model of adrenomyeloneuropathy [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/an-aav9-encoding-human-abcd1-sbt101-shows-functional-improvement-following-spinal-cord-delivery-in-a-rodent-model-of-adrenomyeloneuropathy/. Accessed June 14, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/an-aav9-encoding-human-abcd1-sbt101-shows-functional-improvement-following-spinal-cord-delivery-in-a-rodent-model-of-adrenomyeloneuropathy/