Grant Award Details

CRISPR/Cas9-mediated gene editing of Hematopoietic stem and progenitor cells for Friedreich’s ataxia
Grant Number: 
Project Objective: 
  • The objective of this project is to hold a well-prepared pre-IND meeting with the FDA to discuss IND-enabling plans for the development of gene-edited Friedreich's Ataxia patient hematopoietic stem cells.
  • This work will involve:
  • * pilot pharmacology studies to determine optimal endpoints for the pivotal IND-enabling studies
  • * manufacturing process development
  • * pilot safety/tox studies
  • * develop a clinical protocol synopsis
  • * prepare a pre-IND package and hold a pre-IND meeting
Disease Focus: 
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Award Value: 

Grant Application Details

Application Title: 
  • CRISPR/Cas9-mediated gene editing of Hematopoietic stem and progenitor cells for Friedreich’s ataxia
Public Abstract: 

Translational Candidate

Autologous human CD34+ HSPC of patients with Friedreich’s ataxia, modified ex vivo using CRISPR/Cas9 to remove the GAA expansion mutation in frataxin

Area of Impact

Friedreich’s ataxia (FRDA) for which there is no effective treatment available

Mechanism of Action

The proposed therapy intervention is intended to impact the target indication of Friedreich's ataxia via autologous transplantation of CD34+ HSCs ex vivo gene-corrected using CRISPR/Cas9 technology. The gene-corrected HSC progeny will differentiate into macrophages in injured tissues and transfer functional frataxin to disease cells such as neurons in the brain, and cardiac cells in the heart. This transfer of functional frataxin to endogenous tissue cells leads to long-term tissue preservation.

Unmet Medical Need

FRDA causes neurodegeneration leading ultimately inability to walk as well as heart abnormalities leading to premature death. Gene-corrected HSPC transplantation may represent a one-time life-long therapy that may prevent the neurologic and cardiac complications in FRDA.

Project Objective

Readiness for safety and manufacturing and Pre-IND

Major Proposed Activities

  • Pilot efficacy and safety studies for FDA-required studies readiness for a future clinical trial
  • Manufacturing development for Good manufacturing practice-compatible scale-up process readiness
  • Clinical design of the future clinical trial and pre-IND submission
Statement of Benefit to California: 

Though patients with Friedreich's ataxia in California and the United States are rare, the technology to undergo gene-modified HSCs for autologous transplantation is cutting edge research and utilizes the California resources albeit scientist and laboratories of UCSD, City of Hope, and other CRO organizations in California. Once this technology is studied in the Friedreich's ataxia population, the technology can be used in other applications of mitochondrial disorders.