What do we know about heredity and Huntington’s disease?
Huntington’s disease (HD) is an inherited neurological illness causing involuntary movements, severe emotional disturbance and cognitive decline. In the United States alone, about 30,000 people have HD. In addition, 35,000 people exhibit some symptoms and 75,000 people carry the abnormal gene that will cause them to develop the disease. There is no cure for this fatal disease.
A single abnormal gene produces HD. In 1993, scientists finally isolated the HD gene on chromosome 4. The gene codes for production of a protein called “huntingtin,” whose function is still unknown. But the defective version of the gene has excessive repeats of a three-base sequence, “CAG.” In the normal huntingtin gene, this sequence is repeated between 11 and 29 times. In the mutant gene, the repeat occurs over and over again, from 40 times to more than 80.
This defect causes the resulting huntingtin protein to be malformed, prone to clumping in the brain and causing the death of nearby nerve cells. Cells of the basal ganglia, a brain area responsible for coordinating movement, and of the cortex, which controls thought, perception and memory, are most often affected.
Since the gene that causes HD is dominant, each child of an HD parent has a 50-50 chance of inheriting the HD gene. The child needs only one copy of the gene from either parent to develop the disease. A person who inherits the HD gene, and survives long enough, will sooner or later develop the disease. If the child does not inherit the defective gene, the child will not get the disease nor pass the gene on to subsequent generations. Symptoms of HD generally appear in mid-life.
Research: Unlocking the Mysteries of Huntington’s Disease
The 1993 discovery of the gene, which triggers HD when it malfunctions, jump-started research on this devastating disease. Scientists hope that a multi-faceted approach will lead to a cure.
Research is proceeding in many directions:
- Basic neurobiology: Scientists are continuing to study the HD gene to better understand how it causes disease.
- Imaging: Scientists can observe what the defective gene does to various structures in the brain and how it affects the body’s chemistry and metabolism using PET scanning and other imaging technologies.
- Animal models: Scientists hope to learn more about the symptoms and progression of the disease by breeding laboratory animals, such as mice, and attempting to duplicate the clinical features of HD.
- Fetal tissue research: Investigators have implanted fetal tissue in rodents and non-human primates to better understand how to restore or replace functions typically lost by nerve degeneration in individuals with HD.
- Genetic studies: Scientists are continuing to study inheritance patterns in families, including genetic studies of onset age, inheritance patterns and markers found within families. These studies may shed additional light on how HD is passed from generation to generation.
- Clinical trials of drugs: Drug testing includes classes of drugs that control symptoms, slow the rate of progression of HD or correct or replace other metabolic defects contributing to the development and progression of HD.
New Discovery Offers Hope For a New Treatment
These many avenues of research have recently converged in a promising discovery that suggests a treatment for HD: scientists at the University of California (UC) at Irvine, successfully prevented cell death in a Drosophila fruit fly model that carries the HD gene defect. UC Irvine researchers believe they’ve discovered how the genetic mutation alters chemical pathways to cause the disease. By identifying these changes, researchers believe they may have found an effective way to slow or prevent the disease.
The drug used by UC Irvine researchers to prevent the cell death in the fruit fly is known as an HDAC inhibitor, and is currently in clinical trials for treating cancer in humans. This could speed up human trials of the drug in Huntington’s disease patients.