DOCTOR'S VIEW ARCHIVE

Research on Huntington Disease

Although Huntington disease (HD) attracted considerable attention from scientists in the early 20th century, there was little sustained research on the disease until the late 1960s when the Committee to Combat Huntington Disease and the Huntington's Chorea Foundation, later called the Hereditary Disease Foundation, first began to fund research and to campaign for federal funding. In 1977, the U.S. Congress established the Commission for the Control of Huntington's Disease and Its Consequences, which made a series of important recommendations. Since then, Congress has provided support for research, largely through the National Institutes of Health (NIH).

Research into Huntington's disease includes the following:

Basic neurobiology. Now that the HD gene has been located, researchers are studying the anatomy, physiology, and biochemistry of the nervous system to define how it causes disease in the human body.

Clinical research. Neurologists, psychologists, psychiatrists, and other investigators are improving our understanding of patients' symptoms and progression of the disease while attempting to develop new treatments.

Imaging. Scientific investigations using specialized technologies are enabling scientists to visualize what the defective gene does to structures and chemicals in the brain.

Animal models. Laboratory animals are used to study features of HD.

Fetal tissue research. Investigators are implanting fetal tissue in rodents and nonhuman primates to understand and correct nerve cell degeneration.


Molecular Genetics

For 10 years, scientists focused on a segment of chromosome 4 and, in 1993, finally isolated the HD gene. Scientists anticipate that identifying the location of the HD gene will be a major step toward finding a cure.

Investigators searching for the HD gene evaluated the largest known kindred with HD, 14,000 individuals who live on Lake Maracaibo in Venezuela. By studying these people, scientists can detect patterns of inheritance in interrelated families.

The HD Gene and Its Product

Although scientists know that certain brain cells die in HD, the cause of their death is still largely unknown. The HD gene produces an abnormal version of a protein--which has been (rather confusingly) named huntingtin. The abnormal huntingtin protein causes damage to certain parts of the brain.

The huntingtin protein is actually necessary for life. Investigators hope to learn why the abnormal version of the protein damages only certain parts of the brain. One theory is that cells in these parts of the brain are sensitive to injury by this abnormal protein.

Cell Death in HD

Scientists are paying close attention to the process of genetically programmed cell death that occurs deep within the brains of individuals with HD. This process involves a complex series of interlinked events leading to "cellular suicide." Related areas of investigation include:

  • Overstimulation of cells by natural chemicals found in the brain;
  • A defect in the power plant of the cell, called mitochondria, where energy is produced;
  • Normal metabolism in the brain that produces toxic compounds called free radicals; and
  • Natural chemical substances found in the human body that may protect against cell death.

Several HD studies are aimed at understanding losses of nerve cells that transmit and receive information. Nerve cells in the inner brain area called the striatum are classified both by their size (large, medium, or small) and appearance (spiny or aspiny). The hallmark of HD, scientist are learning, is selective degeneration of medium-sized spiny nerve cells in the striatum. Studies also suggest that losses of certain types of nerve cells and receptors are responsible for the different symptoms and stages of HD.

Clinical Studies of Patients

Clinical studies of patients are in progress to develop new drugs or other treatments to halt the disease's progression. Examples of investigations, using both asymptomatic and symptomatic individuals, include:

Genetic studies on the age of disease onset, inheritance patterns, and markers found within families. Further genetic studies may shed additional light on how HD is passed from generation to generation.

Studies of thinking, intelligence, and movement. Studies of abnormal eye movements, and tests of patients' skills in a number of learning, memory, neuropsychological, and motor tasks may serve to identify when the various symptoms of HD appear and to characterize their range and severity.