Manganism is a disease that arises as a direct result of long term exposure to high levels of Manganese. It is characterized by deposition of Manganese in the brain, and results in mitochondrial dysfunction. The most common treatment is removal from the area with high Manganese exposure, but this doesn’t work for everyone. Luckily, it’s exceedingly rare, effecting so few people every year that there aren’t even statistics on it. Even amongst people that are chronically exposed to high levels, not everyone gets Manganism, which speaks to underlying genetic reasons for susceptibility to the disease. However, these genetic reasons have yet to be identified.
So if it affects so few people, why do we care? It is often compared to Parkinson’s disease, because it presents very similarly. Tremors and muscle weakness are large indicators of late stage Manganism, similarly to Parkinson’s. There is also a large amount of evidence that genes involved with Parkinson’s are related to Manganese uptake, which means that attacking Manganism may provide a pathway for treating Parkinson’s, a much more prevalent disease. There is also evidence that there may be an increase in Parkinson’s cases in areas with high Manganese exposure.
Recent research has suggested that the enzyme Heme Oxygenase-1 (HO-1) is a key player in regulating Manganese levels in the brain. HO-1 is an important regulator of Reactive Oxygen Species (ROS), which are created during normal function of the mitochondria. These are important to get rid of, because they are highly reactive, and can cause a lot of problems if not gotten rid of. Because mitochondrial dysfunction is a major sign of Manganism, it was an important point of investigation. They hoped to find that HO-1 is heavily involved in keeping the mitochondria functional in the presence of high levels Manganese, which would make it a potential therapeutic target for treatments for Parkinson’s and Manganism. While they did find that HO-1 did have a role in mitochondrial recovery after exposure to high levels of Manganese, there was not a complete recovery. This indicates that more research needs to be done to determine other factors that may be at play. One of these might be the SOD proteins, which are also major regulators of mitochondrial Manganese. As a result, while they conclude that HO-1 is a good therapeutic target, I disagree. It seems like it would at best be a partial treatment for these diseases, and there are potentially other players that need to be investigated before designing therapeutics.