Radiomitigators

Treating Radiation Effects

Background

New Amsterdam Sciences is developing pharmaceutical products that can combat the harmful effects of radiation on the body. Called “radiomitigators”, these compounds can help the body repair and recover from damages caused by the high energy radioactivity (ionizing radiation) released by certain radioactive materials, such as those used for cancer radiation therapy, or by nuclear explosions or due to an industrial accident or ‘dirty bomb.’ We are pursuing acquisition, partnership or development of additional technologies for these indications. Regardless of the source of radiation, the effects are similar, so treatments that have commercial applications may also be of value to the U.S. Government to protect citizens and military personnel.

Radiation-Induced Lung Injury (RILI)
Our lead indication for NAS150 as a radiomitigator is to treat the delayed effects to the lung post-radiation. Whether following thoracic radiation for cancer therapy or an unintended radiation exposure, ionizing radiation can cause damage to the lung alveolar epithelium (which line the alveoli where oxygen and carbon dioxide are exchanged) and increase inflammatory cells that secrete profibrotic cytokines and chemokines. The inflammatory response progresses into a condition which reflects the disordered environment of aging and chronic stress. Fibroblasts multiply and infiltrate the normal interstitial tissue of the lung, secreting powerful mediators and undergo evolution to ‘myofibroblasts’ which secrete collagen and which results in a gradual scarring in the lungs, called fibrosis. As approximately 60% of cancer patients receive repeat courses of radiotherapy (RT) during their treatment, many suffer from radiation-induced lung injury (RILI) years after treatment, and for some, it is this, rather than their cancer, which is lethal.

Radiation-Induced Gastrointestinal Syndrome (RIGS)
RIGS is a more acute effect of radiation exposure and can be seen within hours following exposure. The gastrointestinal effects associated with acute radiation exposure – the damage to rapidly multiplying cells lining the stomach and intestines – results in functional compromises that can lead to malnutrition, intestinal ulceration and subsequent infection and can thereby quickly become life-threatening. RIGS can affect individuals exposed to high whole-body doses of ionizing radiation and is a serious risk for individuals undergoing radiation therapy for stomach, pancreatic, or other abdominal cancers. In fact, more than half of patients that undergo radiation therapy for abdominal cancers are affected by RIGS.

Radiation-Induced Oral Mucositis (RIOM)
Radiation induced oral mucositis is an injury resulting from radiation therapy, typically in head and neck cancer patients. Similar to RIGS in that it involves the epithelial cells, it generally starts within 2 weeks of radiotherapy as an acute inflammation and dysfunction of the oral mucosa, which is the inner lining of the mouth, tongue, and pharynx. The resulting xerostomia (dry mouth), even if not progressing to become infected, can severely impact nutrition and hydration if left unaddressed. RIOM can worsen into a life-threatening condition as a result of nutritional deficiencies and/or dehydration. It is reported that up to 80% of patients who undergo head or neck radiation therapy suffer from some degree of RIOM.

Radiation Dermatitis
Also known as radiodermatitis, this is a manifestation of the same processes as described above, but in the skin. The local tissue damage, cellular destruction, and inflammation are common side effects for individuals undergoing radiotherapy for cancer, with more than half of patients developing radiodermatitis during their treatment, although it can also not appear until months, or even years later. Individuals undergoing radiation for cancers of the head, neck, and chest are most at risk due to a higher radiation dose to the skin. Over a prolonged course of treatment, the skin does not have adequate time to heal between each dose of radiation, causing the chronic condition experienced as pain, discomfort, rashes, and radiation burns on their skin.

Radiation-Induced Alopecia and Hair Graying
Radiation-induced alopecia, or hair loss, is a well-known side effect of high dose radiotherapy. Hair loss typically occurs around the area that is being treated but can migrate to areas where the radiation beams exit. Hair growth is extremely sensitive to radiation, due to the growth-related cycling of cells in the hair follicle. Hair loss can either be temporary or permanent, depending on the dose of radiation, and can be accompanied by hair graying. Hair graying occurs when there is destruction or developmental defects of melanocytes (the cells responsible for hair color) and depletion of their stem cells in the hair follicle. Hair loss and graying are significant psychological issues for both women and men undergoing radiation therapy to treat cancer.

For additional information on the products being developed for these indications, please contact us.

 

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