Axonal injury and subsequent neuronal death underpin the pathology of many neurological disorders from acute neural injuries (motor vehicle crashes, combat related injuries, traumatic brain injuries) to neurological diseases (multiple sclerosis, glaucoma). In the central nervous system (CNS), microglia help respond to CNS injuries by mediating the immune response and increasing inflammation at the site of injury. 

Scientists at the National Eye Institute (NEI) have discovered a novel method of reducing neuronal death by using Dimethyl Malonate (DMM), a compound that inhibits the activity of succinate dehydrogenase (SDH). Using DMM on an optic nerve crush model in ground squirrels, DMM helped reduce the pro-inflammatory response of microglia via decreasing succinate levels or reducing the SDH activity. In the same model, treatment also improved the retinal function compared to controls. Additionally, administering DMM after optic crush injury reduced the microglia response and promoted neural protection against axonal injury. 

This method of treats immune-mediated disorders using DMM by decreasing levels of succinate or reducing the activity of succinate dehydrogenase in patients. It inhibits activation of microglial cells by using DMM by decreasing levels of succinate or reducing the activity of succinate dehydrogenase in cells. It prevents the activation of astrocytes in a system comprising of microglial cells and astrocytes using DMM by decreasing levels of succinate or reducing the activity of succinate dehydrogenase. Overall, these results show the promise of DMM for protecting neurodegeneration due to neural injury and possibly other neurodegenerative disorders.

Potential Commercial Applications: 

• Ophthalmic diseases, such as glaucoma
• Neurodegenative diseases, such as multiple sclerosis
• Acute neural injuries

Competitive Advantages: 

• Dimethyl Malonate (DMM) is inexpensive and readily available – reducing manufacturing costs
• Address significant, unmet medical needs since few, if any, treatments exist for neural injuries and neurodegeneration
• Mutation independent method for treating neurodegeneration