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Five Ways To Crash a Mountain Bike

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Quarterly letter from the Department Chair

Summer 2017

There are five ways to crash a mountain bike. These are the Glance, the Graze, the Kersplat, the Kersplat-Graze and the Dismemberment. These differ in kinetic energy and associated injuries. My first shoulder surgery came from a Kersplat. These five mountain biking crashes are “phenotypes”—the visual appearance of an event or a thing.  

In the Kersplat, one flies off the mountain bike and hits the trail, with all of the deceleration occurring at the point of impact. The body is out of whack for a while. In mountain biking, the phenotype is really the last stage of the event. The crash was set in motion long before the final visual element. Hypothetically, a Kersplat might be set in motion by the decision to go off of this cliff.

In Neurological disease, the clinical presentation of the disease is the phenotype.Stroke presents with the acute onset of movement, sensory or language abnormalities. Alzheimer’s disease presents with a decline in memory. Parkinson’s disease presents with slowness of movements. Just like in mountain biking, this disease “phenotype” is actually preceded by a whole series of events. One of the first events in neurological disease is an abnormal gene, or a genetic mutation. The genetic mutation may directly cause the disease that we see, the phenotype. Or a genetic mutation may just be silent in the brain and then a second process hits, such as aging or exposure to a toxin, and then these events combine to cause neurological disease. To understand the cause of diseases, Neurologists need to understand the genes underneath them—to be able to sequence the genes of our patients.

In the next post, “Neurogenomics Center to Accelerate Understanding of Diseases”, we introduce a major new clinical research center in the Department, the Clinical Neurogenomics Research Center, or CNRC. The CNRC will soon sequence the genome of all Neurology outpatients. We will screen for genes that may be causing disease—and were previously unknown. We will screen for genes that may be disease modifiers—genes that do not cause the disease but can determine how fast the disease progresses or whether it will respond to specific medicines. We will study how some patients may get a neurological disease and unexpectedly not suffer a severe phenotype. These patients may progress very slowly in a disease or not suffer the same degree of initial injury. This is called Brain Resilience. If we can understand the molecules that produce resilience to disease, we can identify targets for new drugs. These drugs will alter the molecular events that lead to a disease, and thereby reduce the disease phenotype. Imagine enhancing resilience for a Kersplat!

S. Thomas Carmichael, Chair, UCLA Department of Neurology

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