Acute Radiation Syndrome

Radiation sickness, known as acute radiation syndrome (ARS), is a serious illness that occurs when the entire body (or most of it) receives a high dose of radiation, usually over a short period of time. Many survivors of the Hiroshima and Nagasaki atomic bombs in the 1940s and many of the firefighters who first responded after the Chernobyl Nuclear Power Plant accident in 1986 became ill with ARS.

People exposed to radiation will get ARS only if:

• The radiation dose was high (doses from medical procedures such as chest X-rays are too low to cause ARS; however, doses from radiation therapy to treat cancer may be high enough to cause some ARS symptoms),
• The radiation was penetrating (that is, able to reach internal organs),
• The person’s entire body, or most of it, received the dose, and
• The radiation was received in a short time, usually within minutes.

The chance of survival for people with ARS decreases with increasing radiation dose. Most people who do not recover from ARS will die within several months of exposure. The cause of death in most cases is the destruction of the person’s bone marrow, also referred to the Hematopoietic Syndrome of ARS (HSARS).

Neumedicines has demonstrated that low doses of HemaMax™ (NMIL12-1) administered 24 hours after irradiation can rescue animals from otherwise lethal doses of radiation. To support the R&D of this program, Neumedicines has, to date, secured approximately $33 million in contract revenue from the Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, aimed to support the research and development of HemaMax™ to treat HSARS. The HemaMax™-HSARS program is being conducted under the FDA Animal Rule (21 CFR 601.90-95).

Neumedicines hypothesizes and has demonstrated in preclinical investigation that the administration of HemaMax™ after radiation exposure, including time points of 24 hours or longer, provides significant regenerative function for the human hematopoietic system by not only mitigating the bone marrow damage caused by acute ionizing radiation, but also as a therapeutic that is capable of complete regeneration of multilineage hematopoiesis following lethal radiation.

For more information on Acute Radiation Syndrome visit: www.bt.cdc.gov/radiation/ars.asp

For more information on BARDA visit: www.medicalcountermeasures.gov

For more information on the FDA Animal Rule visit: http://www.fda.gov

Chemotherapy-Induced Thrombocytopenia

Chemotherapy-induced thrombocytopenia (CIT) is a common hematologic toxicity of myelosuppressive and ablative therapy. Thrombocytopenia is defined as a platelet count of less than 150,000uL. Platelets, or thrombocytes, are large fragments from megakaryocytes and are vital for hemostatic activity as well as for maintaining capillary integrity. Thrombocytopenia may occur through decreased production of platelets, abnormal distribution of platelets, and increased destruction of platelets. It is a common complication in patients with cancer, particularly those undergoing treatment with chemotherapy.

Severe or persistent CIT not only has a risk of life-threatening spontaneous hemorrhage, but also may necessitate reduction and/or delay in treatment doses. Allogeneic platelet transfusions are currently the mainstay of treatment for severe or symptomatic CIT, although when to initiate transfusion may be controversial.

Neumedicines hypothesizes and has demonstrated in preclinical investigation that the administration of NMIL12-1 concomitantly with chemotherapy, provides significant regenerative function for the human hematopoietic system by not only mitigating the bone marrow damage caused by chemotherapeutic agents, but also as a therapeutic that is capable of complete regeneration of multilineage hematopoiesis following chemotherapy treatment.

Bone Marrow & Peripheral Blood Stem Cell Transplantation

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patient’s bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrow’s ability to produce the blood cells the patient needs.

Our studies provide support for NMIL12-1’s potential use in hematopoietic stem cell transplantation, currently used to treat lymphomas, leukemias and other hematopoietic malignancies. It is anticipated that use of NMIL12-1, along with a small number of interleukin-12 receptor positive (IL-12R+) hematopoietic stem cells may obviate the need for a conventional peripherally mobilized hematopoietic cellular transplant.

For more information on BMT and HSCT visit: http://www.cancer.gov