Ask the Scientist: Dr. Cynthia McMurray Answers
Paralysis is controlled by motor nerves, which allow the brain to stimulate muscle contraction. These nerves connect to skeletal muscles that ensure locomotion. These nerves are not targeted in Huntington's disease.
I first fell in love with chemistry in junior high school when we learned about simple orbital structure of atoms. This simple chemistry seemed to explain many everyday situations-like why we would use chlorine bleach to clean surfaces and why there was "salt." I found that fascinating and thought that I could explain the way the world worked through chemistry.
Later on in high school, I continued to be entranced. I learned why atoms combined in certain defined numbers and that you could express that number in moles. This explained to me why water was H2O and not some other combination. At that time, I also experienced my first chemistry lab, which really amplified my interests.
In college, organic chemistry hooked me entirely. I loved to synthesize compounds and see them emerge through extraction and drying processes and to test their purity. For example, we extracted caffeine in organic chemistry lab. Just to see this compound—and to know that it made us energetic after drinking coffee or tea—was so exciting. I also loved biochemistry because it made me realize how eating food gives us energy, why we get fat, and why you are thirsty after eating candy. Again, I just thought it explained so much about everyday life (and it does!)
Most definitely. Stem cells have the potential to become any cell. Thus, it is not hard to imagine that a stem cell might be used to develop a brain cell, replacing the lost cell. In fact, every tissue in your body makes stem cells and uses them to replace worn out cells. Stem cells are used regularly as a natural way in which the body maintains healthy cells. Scientists are trying to figure out the process of how a stem cell can turn into a brain cell. If we can figure this out, then we can use stem cells to replace the dying brain cells of people with Huntington's disease.
We know the gene product that causes the disease, and we are beginning to understand a great deal about how the faulty gene product works. What we need now are therapeutic molecules that can interfere with the faulty protein and block its toxic functions.
Currently, several approaches are being tested. One approach is to stop expression of the bad gene. Another is to design therapeutic compounds that can offset the toxicity of the gene product. However, both of these approaches rely on the ability to deliver a gene or small molecules to the affected cells. This is difficult since we cannot easily access the brain tissue. Further, brain cells have a special barrier called the blood-brain barrier, which normally protects the cells against contaminations in the bloodstream. Unfortunately, this protective barrier also prevents many therapeutic agents from delivery to the affected brain regions. Good approaches to drug delivery that do not require surgery or other invasive procedures are needed. New chemical and/or biological methods to mediate oral delivery of therapeutic agents also need to be developed.
While everyone has the HD gene, only a very few have the mutation in the HD gene that causes the disease. The underlying mutation for HD is one in which a few of the building blocks, C-A-G, are repeated too many times in the gene. Thus, the mutation is referred to as "expansion." Unaffected individuals may have 6-25 copies of the building blocks, while those with Huntington's disease have 36 to 120. The longer the number of residues or blocks, the more faulty the gene product is and the more severe the disease. In one affected family, a mother with a CAG repeat number of 55 developed uncontrolled muscle movement at age 35. Her son inherited the faulty gene with an expansion of 72 CAG repeats and developed similar symptoms at age 18.
The mechanism by which the abnormal gene product kills brain cells or why cell death occurs preferentially in select brain regions is poorly understood. However, the mutated gene product creates an unusually "sticky" molecule that can inappropriately bind to and interfere with many cellular molecules and alter their functions. The whole cell goes out of whack and cannot function. The loss of brain cells causes memory deficits and uncontrolled muscle movements that are characteristic of the disease.