Thursday, September 18, 2008

LRRK2

For more than 20 years, my mother has worked with computers at NASA. So, when she developed a pain in her hands the diagnosis seemed easy -- Repetitive Stress Injury. Except that it wasn't so easy. As her mysterious symptoms progressed it varied -- RSI, fibromyalgia (unexplained pain), Lyme Disease, and so forth. It was only after visits to many specialists over a number of years that the diagnosis settled -- Parkinson's Disease. Since there is no clear test for Parkinson's -- it is defined by its symptoms -- we only grew certain as those symptoms developed and as her medications began to alleviate them.

My mother had always been haunted by Parkinson's because her aunt had suffered from it. I had often reasoned with her that since Parkinson's is not hereditary (there is not a strong correlation of Parkinson's incidence among close relatives), she had little to fear.

In 2004, my wife, Anne, introduced me to her future cofounders in 23andMe as they were studying the genetics of Parkinson's Disease. As with my mother's fear, I was skeptical about the study. I reasoned that if there was much to be learned about Parkinson's in the genome, there would have to be a high percentage of inherited cases. In fact, I appeared to be right in that this particular study did not bear immediate fruit.

Nonetheless, there are some cases of familial Parkinson's but they are quite rare. Over the past few years researchers have been honing in on the genes that are responsible for those cases. One gene that stands out in those studies is LRRK2. There is one particular mutation of the LRRK2 gene -- known as G2019S -- that, while rare even among people with the disease, accounts, in some ethnic groups, for a substantial proportion of familial Parkinson's.

As a customer of 23andMe, I have always been excited about the product. I have found what pieces of DNA I share with various relatives. I checked whether other Brins were related. I explored my various gene journals -- learning, for instance, that I have one copy of the fast twitch muscle fiber. I also looked over the health related entries and found that my genetic risk for most diseases is modestly lower than average but for a few diseases it is modestly higher.

Because there are only a small number of genes which are known to have a very substantial effect on health (e.g. 10 times the average risk), I felt the possibility of discovering something very important to my health was just a hypothetical exercise. So, when my wife asked me to look up G2019S in my raw data (23andMe scientists had had the forethought to include it on their chip), I viewed it mostly as entertainment.

But, of course, I learned something very important to me -- I carry the G2019S mutation and when my mother checked her account, she saw she carries it too.

The exact implications of this are not entirely clear. Early studies tend to have small samples with various selection biases. Nonetheless it is clear that I have a markedly higher chance of developing Parkinson's in my lifetime than the average person. In fact, it is somewhere between 20% to 80% depending on the study and how you measure. At the same time, research into LRRK2 looks intriguing (both for LRRK2 carriers and potentially for others).

This leaves me in a rather unique position. I know early in my life something I am substantially predisposed to. I now have the opportunity to adjust my life to reduce those odds (e.g. there is evidence that exercise may be protective against Parkinson's). I also have the opportunity to perform and support research into this disease long before it may affect me. And, regardless of my own health it can help my family members as well as others.

I feel fortunate to be in this position. Until the fountain of youth is discovered, all of us will have some conditions in our old age only we don't know what they will be. I have a better guess than almost anyone else for what ills may be mine -- and I have decades to prepare for it.



For more information on Parkinson's Disease see these organizations I have supported and worked with: Michael J. Fox Foundation, The Parkinson's Institute

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