Animal Models of HDAs more is learned about cellular degeneration in HD, investigators hope to reproduce these changes in animal models and to find a way to correct or halt the process of nerve cell death. Such models serve the scientific community in general by providing a means to test the safety of new classes of drugs in nonhuman primates. NINDS-supported scientists are currently working to develop both nonhuman primate and mouse models to investigate nerve degeneration in HD and to study the effects of excitotoxicity on nerve cells in the brain.
Investigators are working to build
Genetic models of HD using
Transgenic mice. To do this, scientists transfer the altered human HD gene into mouse embryos so that the animals will develop the anatomical and biological characteristics of HD. This genetic model of mouse HD will enable in-depth study of the disease and testing of new therapeutic compounds.
Another idea is to insert into mice a section of DNA containing CAG repeats in the abnormal, disease gene range. This mouse equivalent of HD could allow scientists to explore the basis of CAG instability and its role in the disease process.
Fetal Tissue Research
A relatively new field in biomedical research involves the use of brain tissue grafts to study, and potentially treat, neurodegenerative disorders. In this technique, tissue that has degenerated is replaced with implants of fresh, fetal tissue, taken at the very early stages of development. Investigators are interested in applying brain tissue implants to HD research. Extensive animal studies will be required to learn if this technique could be of value in patients with HD.
Clinical Studies
Scientists are pursuing clinical studies that may one day lead to the development of new drugs or other treatments to halt the disease's progression. Examples of NINDS-supported investigations, using both asymptomatic and symptomatic individuals, include:
Genetic studies on age of onset, inheritance patterns, and markers found within families. These studies may shed additional light on how HD is passed from generation to generation.
Studies of cognition, intelligence, and movement. Studies of abnormal eye movements, both horizontal and vertical, 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.
Clinical trials of drugs. Testing of various drugs may lead to new treatments and at the same time improve our understanding of the disease process in HD. Classes of drugs being tested include those that control symptoms, slow the rate of progression of HD, and block effects of excitotoxins, and those that might correct or replace other Metabolic defects contributing to the development and progression of HD.
Imaging
NINDS-supported scientists are using positron emission tomography (PET) to learn how the gene affects the chemical systems of the body. PET visualizes metabolic or chemical abnormalities in the body, and investigators hope to ascertain if PET scans can reveal any abnormalities that signal HD. Investigators conducting HD research are also using PET to characterize neurons that have died and chemicals that are depleted in parts of the brain affected by HD.
Like PET, a form of Magnetic resonance imaging (MRI) called functional MRI can measure increases or decreases in certain brain chemicals thought to play a key role in HD. Functional MRI studies are also helping investigators understand how HD kills neurons in different regions of the brain.
Imaging technologies allow investigators to view changes in the volume and structures of the brain and to pinpoint when these changes occur in HD. Scientists know that in brains affected by HD, the Basal ganglia, Cortex, and ventricles all show Atrophy or other alterations.
