Bright and early on Saturday morning, Steven Cramer spoke on Genetics and Neural Plasticity After Stroke.
First of all, why should a clinician even care about genetics? A clinician could use a knowledge of genetics to make better clinical decisions regarding treatment options and how to dose (FITT principle) that treatment. Genetics can also help a clinician understand the physiology and pathophysiology of disease. Prediction of outcomes may also be possible with genetics knowledge. In the future, we may be putting patients into research categories based on genetics. So, this is an emerging area of knowledge that clinicians should probably dig a little deeper into for the future.
Steven kindly gave us a crash course in genetics, which was very thorough, thoroughly interesting and thoroughly made my head spin. I’ll just cover the basics, so we understand where this is going clinically. So somewhere way back when, we all learned about DNA alleles: the GATCs in the DNA base proteins. Sometimes there are small genetic mutations that cause one of these base proteins to flip with its paired protein. So for example, a G might become an A. This is called a single nuculeotide polymorphism or SNP (pronounced like ‘snip’) for short. These don’t usually cause any huge difference in the creature in which it occurs, but may make for a different “flavor”. For example, this is what leads to blood type, like say you’re blood type A or AB.
Alright, so let’s look a specific SNP related to stroke neural plasticity. The first one is called BDNF val66met SNP. Don’t ask me what that stands for, no idea beyond the SNP and that BDNF is a chemical that bathes the brain when you’re learning/performing active, real time neural plastic changes. People that have the SNP get less BDNF during learning/plastic changes, show less motor cortex activation on fMRI during learning/plastic changes and are hypothesized to learn slower. However, this does not effect the long term motor outcomes of the individual.
A genotype to be aware of is ApoE4. They tested this from a blood sample. A person who has this gene is less likely to exhibit disability (modified Rankin score of 0-1) than someone who doesn’t have this gene post stroke. There is some interest in doing some statistical magic to see how the relationship between the ApoE4 gene and BDNF val66met SNP may effect motor outcomes after stroke.
Researchers have already looked into this with a combination of 5 different polymorphisms related to dopamine production. Folks with decreased dopamine neurotransmission exhibit poor learning/neuroplastic capabilities, increased rate of depression, poor impulse control. The researchers were hypothesizing that perhaps motor learning/neuroplasticity could be facilitated with the drug L-Dopa. As far as the motor learning, the L-Dopa didn’t seem as important as good old fashion practicing a motor skill in that study.
There was lots of other interesting stuff in the talk, but that’s the meat and potatoes of the clinically applicable stuff in the future when genetic testing is more wide spread. Who needs to go back to Biology 101? I do!