"The demonstration of successful reversal of the disease using purified stem cells with non-myeloablative conditioning offers a novel strategy to treat autoimmune diseases such as lupus with decreased morbidity," said Ramkumar Mandalam, Ph.D., Vice President of Pharmaceutical Operations. "This study also provides further support for our belief that purified stem cells may make it possible to use un-matched donors, such as a parent or non-identical sibling, for a variety of HSC treatment procedures."
"The publication of this preclinical data further validate Cellerant's unique use of pure hematopoietic stem cells for a wide range of therapeutic applications, including lupus and other autoimmune disorders, as well as for cancer and blood disorders," commented Bruce Cohen, Cellerant's President and CEO. "This finding is consistent with recent reports on successful use of hematopoietic stem cell transplantation for the treatment of autoimmune diseases and merits evaluation of pure stem cells in treating such diseases."
Cellerant researchers worked with specialized mice that are prone to an autoimmune condition that closely resembles human SLE. The study evaluated both non-ablative conditioning, which leaves the subject's immune system intact, and fully myeloablative conditioning, which eradicates the subject's immune system, prior to purified HSC treatment. Traditionally, full, and potentially lethal, myeloablative treatment was considered critical for engraftment success. The researchers found that non-ablative conditioning prior to HSC treatment was not only sufficient to ensure engraftment, but the procedure resulted in improved overall survival. The recipient subjects developed durable mixed chimerism, where the resulting immune system was a mixture of donor and recipient cells. Subjects with established autoimmune disease experienced a reversal of symptoms, including decreased appearance of proteinuria, of circulating immune complexes and of auto-antibodies to nuclear antigens.
The donors and recipients in this study were haplo-mismatched, yet successful engraftment was achieved and graft-versus-host disease (GVHD) was avoided. These results suggest that using a HCT treatment that has been purified of all or most host T cells and NK cells may eliminate the need for complete donor/patient stem cell matching. T-cells were not found to be necessary for engraftment in the procedures performed.
Cellerant's highly purified hematopoietic (blood-forming) adult stem cells are isolated from donors or patients undergoing stem cell transplants. This process is designed to provide an improved outcome when used for stem cell transplant indications where a high level of purity is desired or required. After purification, this material contains only stem and progenitor cells, with no detectable contaminating cells such as tumor cells or the T-cells which cause graft-versus-host disease in donor-to-patient transplants. Cellerant is developing hematopoietic stem cells for cancer, genetic blood disorders and autoimmune disease.
Systemic lupus erythematosus (SLE), also called lupus, is an autoimmune disorder characterized by the immune system attacking the body's own tissues and organs, leading to inflammation and damage. The severity of the disease varies, from mild cases only involving the skin to severe cases affecting multiple organs, including the brain. Lupus sufferers experience flares, or intervals of active disease, and remissions in disease. The disease most predominantly occurs in women of childbearing age, but also affects children, adolescents, and men. While the cause of lupus is still unknown, various genetic, environmental, and infectious causes have been associated with its development. Current treatments for lupus vary depending on the extent of the disease, and may change over time. Some medications used to ease symptoms include nonsteroidal anti-inflammatory drugs, antimalarial drugs, corticosteroids, and immunosuppressive medications, though many of these drugs carry their own risks.
Cellerant Therapeutics is a commercial-stage company developing a portfolio of products and services focused on the regulation of the hematopoietic (blood-forming) system. Our products are based on adult hematopoietic stem and progenitor cells as both therapeutic agents and targets for drug discovery. Visit our website at http://www.cellerant.com.
Cellerant Therapeutics, Inc.
Bruce Cohen, 650-232-2122
MacDougall Biomedical Communications
Kari Watson, 508-647-0209