Hematopoietic Stem Cell Gene Editing for X-linked Agammaglobulinemia (XLA)

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Grant Award Details

Grant Number:
Human Stem Cell Use:
Cell Line Generation:
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Grant Application Details

Application Title:

Hematopoietic Stem Cell Gene Editing for X-linked Agammaglobulinemia (XLA)

Public Abstract:
Translational Candidate

Autologous CD34+ hematopoietic stem and progenitor cells (HSPC) with BTK gene insertion for treatment of X-linked agammaglobulinemia (XLA).

Area of Impact

The candidate will provide improved outcomes for patients with XLA, by allowing autologous transplantation with reduced intensity conditioning

Mechanism of Action

The Drug Product has biological activity of hematopoietic stem cells (HSC) to achieve long-term engraftment after autologous transplantation; the BTK gene insertion allows the HSC to support normal B lymphopoiesis to restore protective antibody production.

Unmet Medical Need

Despite the life-saving improvement in health of XLA patients afforded by chronic immunoglobulin replacement therapy (IgRT) injections every 3-4 weeks, autologous HSC gene therapy could provide a one-time long-term health benefit by conferring the ability for the patient to make antigen-specific antibody responses, including IgA/IgM and relieve the need for life-long IgRT.

Project Objective

A pre-IND meeting will be held.

Major Proposed Activities

  • Establish optimal BTK gene insertion protocol for manufacturing clinical Drug products
  • Demonstrate disease modifying efficacy of BTK gene insertion in XLA patient CD34+ HSPC
  • Prepare clinical protocol and other reguatory documents to hold a pre-IND meeting
Statement of Benefit to California:
The proposed research will lead to a curative autologous HSC gene therapy for XLA. With an estimated prevalence of 3/1,000,000, there would be ~100 people in California with X-linked agammaglobulinemia, of whom a predicted 98% would benefit from and be eligible for this treatment.