Gene Therapy for SLC6A8 Creatine Transporter Disorder

Return to Grants

Grant Award Details

Grant Number:
Human Stem Cell Use:
Award Value:

Grant Application Details

Application Title:

Gene Therapy for SLC6A8 Creatine Transporter Disorder

Public Abstract:
Research Objective

The objective is to define a final therapeutic candidate for an effective gene therapy for mutations of the creatine transporter SLC6A8, a major cause of X-linked intellectual disability (ID).


This disorder results in severe ID, autistic-like behavior, seizures, & lack or delay of speech with no treatment. Improving brain transduction is essential and widely applicable to other conditions.

Major Proposed Activities

  • Develop multiple adeno-associated viral (AAV) vectors expressing human SLC6A8, package, determine titers and expression in human induced pluripotent stem cell (hiPSC)-derived neurons in vitro.
  • Assess resolution of any deficits and improvement in creatine transport in SLC6A8-mutated hiPSC-derived neurons by vector-mediated expression.
  • Assess transduction efficiency of AAV-SLC6A8 in vivo with brain cell expression and distribution of vector copies and tissue creatine levels in non-brain organs and tissues in Slc6a8-mutated mice.
  • Assess disease modifying activity of AAV-SLC6A8 in the a murine Slc6a8-mutated model.
  • Determine final therapeutic candidate, complete draft target product profile, and develop assays of purity, activity and identity.
  • Request INTERACT meeting.
Statement of Benefit to California:
Genetic-based intellectual disability of all causes is a more common occurrence than is appreciated. Effective therapies for these intellectual disabilities, where often there are none, could improve the lives of thousands of afflicted Californians & their families along with many hundreds of thousands of afflicted people worldwide. Brain gene therapy may result in novel, effective treatments for these disorders & improvement in their quality of life, with applicability to other conditions.