The Fifty Plus Racing Foundation has a global reach.
Duke University recently published a report on a study suggesting a hopeful direction for continued research. In an earlier post, we asked Dr. Justin Body of Cambridge, MA to share his perspective on what this may means as we race for cure to Alzheimer's Disease.
We also sought a perspective from a friend of the Fifty Plus Racing Team in Australia who is also actively engaged in neurobiological research. Dr Ross Grant is Clinical Associate Professor, Sydney Medical School and CEO of the Australasian Research Institute, Sydney Adventist Hospital.
Dr. Grant informs,
This is an interesting paper showing that in their genetically modified mouse model they found that activity of the enzyme Arginase was increased resulting in overall decrease in the brain concentration of the amino acid Arginine.
They found that when they inhibited Arginase, Microglial CD11C was significantly decreased, which correlated with reduced Alzheimer's Disease pathology.
Interestingly they also suggest that some of their genetic markers suggested a down regulation of the immune response.
At the risk of getting a too technical, this comment may be a bit misleading. The reduction in pathology associated with the arginase inhibitor was associated with a decrease in the number of CD11c Microglial cells. That is, there were fewer immune cells, meaning reduced immune activity, only after the inhibitor drug was applied.
More immune cells were linked to more brain damage.
Put simply: The Alzheimer's Disease pathology was again reduced when the number of immune cells was reduced. This is similar to what others have found.
In relation to an Arginase inhibitor being a potential new drug for preventing Alzheimer’s Disease:
1. Arginine is an important precursor to the vasodilator and neuroactive molecule nitric oxide so having more in the brain and vasculature is likley to be a good thing.
2. Inhibiting Arginase in the longer term may be a problem as a) Arginase is an important enzyme used in the body as the final stage in the metabolic pathway to excrete excess nitrogen in the urea cycle (through urination). If you inhibit Arginase too much you build up toxic molecules like ammonia which (among other things) can also cause dementia. Researchers would need to develop a protocol that was able to specifically target Arginase in the brain.
Having noted the positive benefits of increasing Arginine in this mouse model and accepting that an element of this mechanism will likely be transferable to the human condition, I am somewhat skeptical that—
1. The technical issues mentioned above will be overcome easily, and
2. Low Arginine will be the major biochemical anomaly in the brain of human Alzheimer's Disease patients.
The evidence strongly suggests that the biochemical anomalies in the human Alzheimer's Disease condition are more complex than just Arginine deficiency. It needs to be dealt with as such.
Apologies for the essay but as is often the case it is hard to give a simple answer to some of these questions.
Also, thank you for the activity of the Fifty Plus Racing Foundation to cure Alzheimer’s—raising money to support scientists, and comfort care givers—awarding grants to unfunded care givers.
And thank you Dr. Grant for your commitment to your research and your support of the Fifty Plus Racing Foundation!