What is severe Pyruvate Kinase Deficiency (PKD)?
PKD is a congenital non-spherocytic hemolytic anemia that results from a mutation in the PKLR gene, which encodes the red blood cell (RBC) enzyme, pyruvate kinase (PK). Pyruvate kinase is responsible for catalyzing the final adenosine-triphosphate (ATP)-generating reaction of the glycolytic pathway in RBCs. Loss of this enzyme impairs RBC metabolism, decreases its lifespan and leads to anemia. In addition to anemia and chronic fatigue, patients also experience jaundice, cholelithiasis, and extramedullary hematopoiesis resulting in splenomegaly.
What is the purpose of this PKD gene therapy clinical trial?
This study is an open-label Phase I trial to assess the safety and feasibility of a gene therapy product consisting of autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a lentiviral vector encoding for the PK enzyme. As a result of the investigational gene therapy treatment, the gene-modified HSPCs are expected to give rise to new RBCs containing the functioning PK enzyme. This functional correction will hopefully render the cells resistant to destruction, leading to improvement in red blood cell lifespan, subsequent correction of anemia, and reduction or elimination of the need for blood transfusions.
Who is eligible to participate in the gene therapy clinical trial?
PKD patients with a confirmed PKLR mutation and severe, transfusion dependent anemia despite splenectomy are eligible for the trial. The first cohort to be enrolled will include 2 adult patients (≥18 and <45 years old). Once safety has been established in this initial cohort, older pediatric patients (≥12–17 years), followed by younger pediatric patients (≥8–11 years) will be enrolled.
What does participation in the PKD gene therapy clinical trial involve?
Following screening of patients to confirm eligibility for the trial, participation in the study will involve:
- Mobilization and Collection of HSPCs: Mobilization is performed via administration of granulocyte-colony stimulating factor (G-CSF) and plerixafor (AMD-3100) over several days and collection is performed via peripheral blood apheresis, which may require a temporary central catheter.
- Infusion of Genetically Modified Stem Cells (i.e., the Investigational Gene Therapy): Following ex vivo transduction of HSPCs with the LV encoding for the PKLR gene and busulfan conditioning, the genetically modified HSPCs are infused into the patient.
- Follow-up after Administration of the Investigational Gene Therapy: Patients will need to return for follow-up visits, including blood and bone marrow tests, over the next 2 years. In addition, patients may expect to have long-term follow-up with their home physician approximately 1-2 times per year for another 13 years.
How much will it cost to participate in the trial?
Financial support, including travel arrangements and housing accommodations for patients and a family member, both for the treatment and follow-up visits, will be provided. This will also include assistance with medical visas and translation services for patients and families if they are needed.
To learn more about the PKD gene therapy clinical trial email: