How does ARU-1801 work?
SCD is an inherited blood disorder caused by mutations in the HBB gene, which provides cells with the genetic instructions necessary to make hemoglobin. Hemoglobin is a protein in red blood cells that binds oxygen. Mutations in the HBB gene can lead to hemoglobin being made incorrectly. This causes red blood cells to adopt a “sickle” shape, instead of the usual disc shape. The sickled cells stick to each other, blocking blood flow — especially in small blood vessels.
ARU-1801, using a proprietary technology, is designed to increase the number of functional red blood cells. It does so by inserting a modified version of the HBB gene directly into the patients’ own (autologous) hematopoietic stem cells, or stem cells that give rise to red blood cells.
The modified gene encodes for a protein called fetal hemoglobin. This protein is naturally present in the human body before birth, but the gene encoding for it is “switched off” in adults. In ARU-1801 treatment, the gene encoding for fetal hemoglobin is inserted into patients’ stem cells using a special vector or transport agent called a lentivirus.
Prior to ARU-1801, a patient’s cells are collected to be treated with the lentivirus carrier, thereby modifying them genetically. The patient then needs to undergo a reduced-intensity conditioning (RIC) regimen, involving chemotherapy and/or radiotherapy, to clear their body of “defective” blood-forming stem cells and prepare them for the introduction of the genetically modified cells.
RIC is associated with fewer and less severe side effects compared to high-intensity myeloablative regimens, in which the patient’s bone marrow (where stem cells giving rise to blood cells reside) is destroyed prior to introducing genetically modified cells.
ARU-1801 in clinical trials
An open-label Phase 1/2 clinical trial (NCT02186418) is now recruiting up to 10 SCD patients, ages 3 to 35, in the U.S., and Jamaica to test the safety, feasibility, and efficacy of ARU-1801.
Cells will be harvested from enrolled patients, treated with ARU-1801, and then reintroduced to the patients following an RIC regimen. Patients will be evaluated for up to 15 years after the treatment to assess its safety and efficacy. If successful, researchers will be following patients to assess whether a single treatment is sufficient over a lifetime, or, if not, how frequently patients need to be treated.
Last updated: Jan. 27, 2020
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