Ex vivo Engineering of Autologous Hematopoietic Stem Cells for the Treatment of Hypophosphatasia

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Grant Application Details

Application Title:

Ex vivo Engineering of Autologous Hematopoietic Stem Cells for the Treatment of Hypophosphatasia

Public Abstract:
Therapeutic Candidate or Device

Hematopoietic stem/progenitor cells collected from patients with hypophosphatasia and genetically modified with a lentiviral vector to release TNALP


Hypophosphatasia (HPP)

Therapeutic Mechanism

We are proposing a cell-based enzyme replacement therapy for HPP: autologous gene-modified hematopoietic stem/progenitor cells (HSPCs) will be infused into the patient and will engraft into the bone marrow. Transplanted cells will then continuously release tissue-nonspecific alkaline phosphatase (TNALP), which is the enzyme deficient in patients with HPP.

Unmet Medical Need

The only approved enzyme replacement therapy (ERT) for HPP requires multiple and expensive weekly injections for life and is associated with compliance issues due to common site injection reactions. We are proposing a more affordable, one-time and stable cell-based ERT treatment for HPP.

Project Objective

IND submitted

Major Proposed Activities

  • Optimize the clinical manufacturing of the therapeutic product
  • Complete toxicity and efficacy studies in cell culture and in mice
  • Complete the regulatory requirements to initiate a Phase 1/2 clinical trial
Statement of Benefit to California:
Hypophosphatasia (HPP) is a rare and sometimes fatal metabolic disease due to deficiency in the enzyme TNALP, a key regulator of mineralization. Although a synthetic enzyme replacement therapy called STRENSIQ exists, only a subset of insured patients with early disease onset are eligible. STRENSIQ is one of the most expensive drugs in the world and requires frequent and often painful injections for a lifetime, affecting compliance. We are proposing a one-time ex vivo gene therapy for HPP.