In The Thick Of The Hunt For Huntington’s Disease

2010-08-01 | |
Last updated: 2010-08-01

Serious genetic conditions are usually rare because throughout human history they would have typically taken the life of individuals before these people could reproduce and pass along their genetic mutation. However not all genetic conditions affect people in early life and those disorders that more frequently affect people in the later stages of life have a greater chance of being passed on to children. One such very well known genetic condition is the degenerative, fatal disorder called Huntington’s Disease (HD).

Huntington’s Disease or Huntington’s Chorea, as it was once known, is a genetic disorder that affects the whole body, but has the most severe effects on the mind. In the brain, the disease causes a progressive death of specific nerve cells that results in a loss of mobility and mental capabilities. As the disease takes its toll, it eventually leaves patients both physically and mentally incapable of caring for themselves before causing them to die from disease complications.

In contrast to many genetic disorders that affect individuals from birth, this condition usually shows symptoms when people are between 30 and 50 years of age, though it can also appear in the very young or in those with advanced age. As a genetically dominant characteristic, children with one parent affected by the disease have a 50% chance of also developing it. Huntington’s occurs most commonly in those with a Western European ancestry.

Once thought to be a very rare disease, Huntington’s is being more readily diagnosed and a recent study by the London School of Hygiene & Tropical Medicine suggests that the condition could affect at least 1 in 8000 people. This means that in the US, the disease potentially afflicts almost 38000. In the UK, there could be 8000 people affected and in Canada there could be as many as 4100. Because the condition is rare and under diagnosed, many people who have the condition might not even know about it.

In terms of genetic complexity, the disease is relatively simple as it is caused by a genetic defect in a single gene of our DNA that is active throughout our bodies. The abnormal gene responsible for Huntington’s Disease was identified in 1993 and shortly following that, a genetic test was devised to allow individuals showing symptoms to determine accurately whether they are affected by the disease.

Although Huntington’s Disease is a rare disorder, numerous researchers are directing considerable attention toward the disease and making significant advances in understanding it. This is good news because despite being caused by mutation isolated to one gene, there is still significant complexity in attempting to understand the disorder in order to find a way to stop its path of destruction. To this end, researchers are approaching the problem from many angles and consequently making a variety of important discoveries.

One such interesting discovery comes from the University of California working with a number of other institutions. The scientists found a single molecular switch in mice that triggers the onset of Huntington’s symptoms. This switch is located on specific versions of a protein that is created abnormally because of the Huntington’s genetic defect.

This discovery is very important because it helps to explain why those with the genetic defect do not automatically have the condition; the molecular switch on the defective protein must be flipped on. More importantly for patients, it suggests that finding ways to keep the switch flipped off could slow or prevent development of the condition.

Another important discovery, this time from the University of Melbourne, is that this same abnormal protein tends to form clusters within the nerve cells and this, in turn, reduces their ability to move materials around inside them. Subsequently, this limits the ability of the neurons to create connections with other nerve cells and contributes to the death of the nerve cells.

This finding is interesting because unlike some other degenerative diseases of the brain in which proteins continually accumulate in the nerves, the researchers found that the undesirable protein was not accumulating all the time. This means that the mere existence of such protein clusters in a nerve cell is enough to stress the cell and cause it to eventually die. It also means that drugs that could prevent formation of these clusters could be of considerable benefit.

Relating to these accumulations of abnormal proteins, Yeshiva University researchers have found that the abnormal protein may stay longer in cells than normal versions of the proteins because it is difficult to cleanup. Their research found that these proteins regularly stick to the containers used to transport them to the enzymes that would normally break them down. The result is that it becomes difficult to remove the abnormal proteins that do accumulate inside the cells.

Another finding from the Buck Institute for Age Research also relates to the normal breakdown of this protein. In this case, the researchers found that the enzymes in the cells responsible for breaking down and recycling the proteins were chopping the proteins into fragments that are toxic to the nerve cells.

Subsequently, their research enabled them to identify the specific enzymes that were creating the toxic fragments. By reducing the effectiveness of these enzymes, the researchers were able to reduce the creation of the toxic protein fragments. This is very good news because it suggests yet another way in which the disease could be slowed.

With the heightened levels of these abnormal proteins and their toxic byproducts within the nerve cells, another important area to understand is the damage that these materials have on the cells. To that end, research from Rockefeller University identified that the abnormal protein and its toxic breakdown products cause DNA damage and also reduce the ability of cells to repair the DNA.

Importantly, the research efforts found that increasing the concentrations of materials responsible for DNA repair limited the damage resulting from the condition. This finding is important because it suggests yet another way to prevent cell death associated with the disease.

Though Huntington’s disease involves a relatively limited amount of genetic mutation, the complex results from this genetic defect are profound both at the cellular level and for the lives of patients. Fortunately, research efforts from numerous sources are building an impressive level of understanding regarding the condition. This means that opportunities ranging from preventing the onset of Huntington’s to limiting the damage that the disease does are all being advanced rapidly offering the hope that the condition can be vanquished sooner rather than later.

If you have or are at risk of Huntington’s or have experienced the devastating effects of the disease in a loved one, consider sharing your experiences in the health forums.

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