LAUSR

Urate (sometimes referred to as uric acid) is a naturally occurring antioxidant (5,6). Interest in urate as a possible neuroprotective agent began when researchers noted that high urate levels are associated with lower risk of developing Parkinson’s disease (7–9) and Alzheimer’s disease (10). Naturally occurring high levels of urate are also associated with slower disease progression in Parkinson’s disease (11–13). The biological mechanisms that cause ALS are not completely understood, but they are likely to include damage to the motor neurons from oxidative stress, as supported by both autopsy and laboratory studies (14). It follows that antioxidants such as urate (or agents that increase levels of these such as inosine) might theoretically be neuroprotective in ALS. Some (15–18) but not all (19–22) studies find that high urate is associated with prolonged survival in PALS. Further database analyses and clinical trials are underway to try and clarify this. Beyond just neuroprotection via urate elevation, recent work suggests that inosine can stimulate the growth of axons in culture, promote collateral sprouting in the corticospinal tract, and even enhance motor recovery after traumatic brain injury (23). These observations suggest that inosine might be able to enhance reinnervation in ALS. ALSUntangled assigns a TOE ‘Mechanism’ grade of C based on this information (Table I).