Acute Radiation Syndrome
During recent years, the threat of nuclear detonation on U.S. soil has increased. The lack of effective post-exposure treatments for victims experiencing Acute Radiation Syndrome (“ARS”) presents a serious problem for public health planners.
Acute Radiation Syndrome is characterized by a series sub-syndromes affecting different organs and systems in the body.
Acute Syndromes – H-ARS
Radiation exposure kills rapidly dividing cells very effectively. The human body’s hematopoietic system is comprised of several different types of rapidly dividing cells that make up the immune system. After exposure to high-dose radiation, the numbers of these different cells drop quickly due to radiation-induced cell death. This is known as the hematopoietic sub-syndrome or H-ARS. The rapid decline in immune system cell counts leaves the patient open to severe infection. The onset of the syndrome is rapid, usually within 24-48 hours after exposure and death can occur within 7-10 days.
H-ARS is currently treatable using a class of drugs called granulocyte colony stimulating factors or G-CSFs. G-CSFs increase the production of new cells in the bone marrow allowing the immune system to be replenished. Studies performed by NIAID have demonstrated a significant increase in survival at high doses of radiation after the administration of G-CSFs.
Neupogentm (Amgen) is currently being stockpiled by BARDA in the Strategic National Stockpile under a vendor-managed supply agreement. In addition, BARDA is funding the advanced development of Leukinetm (Sanofi) as an alternative for procurement in this class of drugs.
Acute Radiation Syndrome – GI-ARS
At higher doses of radiation, a second sub-syndrome develops in the gastrointestinal (“GI”) tract. The mucosal layer that lines the gut dies and is sloughed off, reducing the body’s ability to absorb nutrients from food. In addition, important stem cells in the GI tract are often damaged, reducing the ability of the body to replenish the lining of the gut and restore normal function. Onset of the syndrome is rapid, usually within the first 2-24 hours and death can occur in 3-10 days.
There are no treatments for GI-ARS. The current standard of care is limited to supportive measures such as fluids and antibiotics. There are other compounds under development for this sub-syndrome with various mechanisms of action. Because GI-ARS is a complex syndrome, it is likely that multiple drugs will be required to treat.
Acute Radiation Syndrome – Lung-ARS
Experience with nuclear accident victims has demonstrated that patients can survive H-ARS and GI-ARS with the administration of G-CSFs and supportive care. Unfortunately, those patients often succumbed to respiratory failure caused by inflammation and then scarring of the lung. This is the lung sub-syndrome or Lung-ARS and its effects are not apparent until two to three months after exposure.
Lung-ARS is characterized by a delayed onset of inflammation in the lungs called pneumonitits. This inflammation leads to the development of scar tissue called fibrosis. The combination of inflammation and scarring reduces lung function and leads to death.
The goal of BARDA in developing medical countermeasures for radiation is healthy, long-term survival for as many citizens as possible. While treatment with Neupogentm and supportive care can help victims survive the short-term syndromes, H-ARS and GI-ARS, long-term survival is dependent on effective treatment for Lung-ARS.There are no current treatments for Lung-ARS. AEOL-10150 is the only drug under advanced development by the U.S. Government for this syndrome. We are not aware of any compounds under development that have shown efficacy in Lung-ARS when administered after exposure to acute, high dose radiation.