We may have to thank body builders for the next big breakthrough in the battle against Parkinson disease. Companies that market powders and potions to those obsessed with their glutes and pecs claim that the dietary supplement creatine changes physiques. However, the NIH National Institute of Neurological Disorders and Stroke (NINDS) recently announced a phase III clinical trial examining the ability of creatine to slow symptom progression in people with Parkinson disease.

Although its body-bulking effect may be caused by simple weight gain, creatine is thought to boost exercise performance. Phosphocreatine donates phosphate groups to ADP, increasing the supply of ATP available in muscle, which allows muscles to work longer and harder.

Creatine is also neuroprotective. Klivenyi et al. reported that creatine prevented neuron loss but did not affect muscle weight in a mouse model of ALS. Zhu et al. reported that ischemia caused smaller stroke volumes in mice treated with creatine relative to vehicle. Ischemia induced less cytochrome c release and caspase activation in creatine-treated relative to vehicle-treated mice.

Creatine performed well in small clinical trials. Now NINDS plans to study 1720 people in the early stages of Parkinson disease in a double-blind study of creatine’s effects. This study, the first of a series of clinical trials called NIH exploratory trials in Parkinson disease (NET-PD), is slated to last five to seven years.

In response to my comments, Juan Carlos Lopez had this reply on Spoonful of Medicine:

Candidate genes? We already have many more candidate genes than we know what to do with. I’d argue that candidate genes are, in fact, part of the “genetic noise” Debra refers to.

What this field needs is, among other things, new animal models that allow us to make more thoughtful experiments on the biological basis of psychiatric disease.

In the absence of good models in which to test the functional relevance of whatever genes the screening process identifies, the massive investment that Apoorva highlighted will bring rather paltry returns.

He makes an excellent point, but I’m sticking to my guns. Groups of genes that are subtly affected (not wiped out entirely) would not have been found in the small populations studied thus far. Furthermore, the absence of good animal models underscores the need for more information on variation in the only disease model we have: the human.

We can agree to disagree. Although I’m a huge, geeky fan of hers, I have to respectfully disagree with Apoorva’s post on Spoonful of Medicine about the Stanley Medical Research Institute’s $100 million gift to the Broad Institute (originally reported in the Boston Globe). The Broad Institute, which is arguably the be all and end all of genomics research, plans to compile genetic and clinical data from thousands of people in order to identify candidate genes that associate with psychiatric disorders, including schizophrenia and bipolar disorder. Apoorva said:

But these are extremely complex disorders, each involving multiple genes. What roles do those genes play in the disease? Without understanding how the different genes interact and what the impact is of the different variations, the data will be all but meaningless.

I would argue that the very complexity of these diseases is the reason that such large datasets (and the bioinformaticians to make sense of them) are necessary. A really good example is in this month’s Nature Genetics. The Autism Genome Project Consortium identified new gene candidates associated with autism from a dataset containing genetic information from nearly 8000 people. Have they poof! figured out what causes autism? No, but they have identified a place to start.

Finding a place to start is really the whole point. These are disorders for which there just isn’t a lot to go on. Apoorva’s concern about understanding the roles of candidate genes in health and disease is really putting the cart before the horse. The molecular interactions between disease-related genes and their roles in psychiatric disorders can only be deciphered once candidates are in hand. With this fantastic grant, maybe the Broad Institute will get that far. That would really be something.

In case you missed it, the New York Times profiled Joseph LeDoux’s rock band, which is appropriately named the Amygdaloids. The band’s fans may be even more impressive than its members, who are all neuroscientists. Nobel prize-winning mathematician John Nash (subject of A Beautiful Mind) describes the Amygdaloids music as “psychoanalytic”.