In addition to cancer, renal/cardiovascular, and autoimmune diseases, AIMs have the potential to treat a number of other diseases that are linked with inflammation, oxidative stress, and aging. These include applications in Transplants, Respiratory Disease, and Neurodegenerative Diseases.
Transplanted organs are at risk of failure due to ischemia-reperfusion injury associated with the transplantation process, as well as rejection by the recipient’s immune system. Conversely, patients receiving bone marrow transplants may suffer from graft-versus-host disease, in which transplanted immune cells attack normal tissues of the recipient. Consequently, transplant patients routinely take immunosuppressive drugs, which increase the patient’s susceptibility to infection and are frequently associated with kidney damage.
In preclinical studies, AIMs provided potent protection against renal ischemia-reperfusion injury and against graft-versus-host disease, suggesting they may be useful in preventing both acute and chronic transplant failure. AIM molecules are in preclinical development for transplant indications. Multiple AIMs have proven effective in animal models of graft versus host disease.
Major respiratory diseases including asthma, chronic obstructive pulmonary disorder (COPD), and cystic fibrosis all involve chronic oxidative stress and inflammation. Recent research has highlighted the importance of the Nrf2 pathway in protecting the lungs against inflammatory insult, and highlighted Nrf2 activation as a promising therapeutic strategy for treating major respiratory disorders.
AIM molecules have shown significant activity in preclinical models of asthma, acute lung inflammation, COPD, and cystic fibrosis. AIMs are in preclinical development for respiratory indications.
Neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ALS are now understood to have a significant inflammatory component. Chronic oxidative stress and activation of inflammatory signaling pathways (including the NF-kB pathway) are believed to play a major role in the pathology of these disorders. For example, NF-kB activation has been shown to increase the production of beta-amyloid, the suspected pathogenic protein in Alzheimer’s disease, and brains of Alzheimer’s patients have been shown to contain highly elevated levels of inducible nitric oxide synthase (iNOS), a major NF-kB target gene. Similarly, Nrf2 activation has produced beneficial effects in models of Huntington’s disease and ALS.
Because AIMs are known to activate Nrf2 and inhibit microglial activation, NF-kB activation, and iNOS expression, they have the potential to become significant new treatments for these intractable diseases. Preclinical studies have identified AIMs that are particularly efficient in reaching effective concentrations in the CNS, and several of these have shown significant activity in models of Alzheimer’s, Parkinson’s, and Huntington’s disease. These molecules are in preclinical development. |
