Since 1979, the U.S.-Venezuela Collaborative Research Project, a team comprised of top international doctors and scientists, has been traveling each year to very poor, rural fishing villages along the shores of Lake Maracaibo, Venezuela. We are searching for a cure for a disorder called "Huntington's disease (HD)." HD is a dominantly inherited, neurodegenerative disease for which there is no treatment. Each child of a parent with the disorder has a one in two chance of inheriting the same lethal affliction. HD is a very downwardly mobile illness. It usually strikes between the ages of 30 to 40, in an individual's prime productive years. Most individuals in the late stages of illness require enormous assistance. They lose the ability to walk, talk, feed themselves, but are still conscious, aware and know themselves and their families. It can appear as young as 2 years of age and as old as 80 years.
Venezuela has the highest concentration of Huntington's disease in the world, particularly focused in the State of Zulia. The world's largest family with Huntington's disease lives along the shores of Lake Maracaibo. The original progenitor of this family lived in the early 1800's and left more than 18,000 descendants (more than 14,000 of whom are currently living), many of whom are either affected by the illness or at risk for this devastating and inevitably fatal neurodegenerative disease.
This pioneering collaborative research in Venezuela and the United States has led to critical breakthroughs in understanding genetic disease and medical science. A few of the highlights of the research are as follows:
- In 1983, the location of the Huntington's disease gene on chromosome 4 was found using then-unknown techniques of recombinant DNA technology. Our successful demonstration that these new scientific strategies could be used to locate disease genes opened the door for finding genes causing all different kinds of disorders, including cancer - breast, prostrate, colon and lung - heart disease, arthritis, psychiatric disorders and many more. Research still goes on to find genes predisposing to other diseases.
- In 1993, the gene for Huntington's disease itself was discovered, leading to a dramatic re-assessment of the nature of this disease. Huntington's disease was found to be caused by a piece of a gene that expands abnormally. The capture of the Huntington's disease gene confirmed the presence of a newly discovered family of diseases all caused by an abnormal elongation of a gene. Almost all of these diseases are fatal and almost all affect the brain. They tend to be of later onset. We also discovered that Huntington's disease can begin in a family with no previous history, usually as a result of a mutation in the male germ line.
- The tissues from these families with Huntington's disease in Venezuela are now located in international cell banks and are studied by investigators worldwide to understand more about human genetics in health and disease.
- The study of tissues from these families has already led to the discovery of genes for Alzheimer's disease, dwarfism and cancer. The Venezuelan Huntington's disease families have been described in every recent genetics textbook and have been frequently presented in the United States and Venezuelan media.
In stark contrast to all they have given the world, these families suffer from extreme poverty, deprivation and duress. They are subject to all of the diseases and devastation of small impoverished fishing villages. In addition, in almost every home, there are people in various stages of Huntington's disease, from the initial aberrant movements to the prolonged bed-ridden agonal years wracked by unceasing motion but aware and conscious. The children do not go to school because they must care for many relatives incapacitated and dying at the same time. The six year olds must earn a living; by age thirteen they are parents themselves. The density of this illness predisposes toward two individuals with the illness having children. The risk to these children is three chances in four. If they both inherit two Huntington's disease genes, 100 percent of their children will become affected.
Our research and collaboration with this family has been essential to solving many of the scientific puzzles of Huntington's disease. They have helped tremendously in defining the natural progression of the illness from a neurological and neuropsychological perspective and in localizing the Huntington's disease gene through linked markers in 1983 and isolating the gene in 1993. Without the help of this Venezuela kindred, families around the world who suffer from Huntington's disease would see very little hope for a cure.
Again, unfortunately no treatments or cures have yet been found. While researchers are toiling day and night in their laboratories, developing transgenic mice, examining brain tissue and looking for treatments, the Venezuelan families, as well as families in the U.S. and throughout the world, continue to suffer and die from this dreadful disease.
Dr. Margot de Young is a Venezuelan physician who, since 1991, has been working with the Hereditary Disease Foundation as the Director of Research and Treatment for our Project in Venezuela. She has devoted herself whole-heartedly to helping these families. Dr. Margot de Young is our guardian angel and saint. She runs the Casa Hogar Amor y Fe (House of Love and Hope). The Casa Hogar Amor y Fe was her brainchild. She helped turn what was a bar called "El Toro Rojo" (the Red Bull) - one of the worst in the city of Maracaibo Ð into a haven for Huntington's disease families.
The purpose of the clinic is manifold. It serves a completely neglected and overlooked population with no access to medical care. Most of the Venezuelan Huntington's disease family members have never received any information and education about the importance of basic primary medical care. Also, hospital patients must pay for all their supplies - including pins for surgery - and are sent home even in extremis. Few, if any, physicians would volunteer to make house-calls to these neighborhoods, which have been deemed "impenetrable" even by the police.
In the Casa Hogar there are beds for 34 patients, but Dr. de Young manages to accommodate as many as possible by creatively using every ounce of space there is. The Casa Hogar feeds many of the hundreds of families coming to its door. Huntington's disease causes people to be even more starving and often people die of starvation. Dr. de Young provides as much medical care as she can with medicines she can buy in Venezuela as well as those which we send to her. The clinic provides families with basic primary care services such as immunizations, anti-parasite treatments, hygiene and nutrition education, and birth control education and distribution.
Another facet of the clinic is for individuals in the later stages of Huntington's disease who are unable to care for themselves. Medical care is provided along with three meals a day, clean, running water, and clean beds.
Young children and adolescents who have juvenile HD, most of whom suffer from seizures, have a place to receive care. The average family size in these villages is about ten children, making caring for even one child with Huntington's disease a challenge, much less many who are sick. But because HD is a dominantly inherited disease, often families with twelve children will have six to eight children suffering from the disease. Care is virtually impossible at home. The clinic provides a place where those too sick to remain at home Ð both children and adults Ð can receive proper medical care and attention.
Dr. de Young maintains a rule that any family member who can do the job has first priority in being hired. All of the staff, with the exception of Dr. de Young herself, come from families with Huntington's disease. They are extremely proud of their work, they keep the place and their own uniforms spotless under Dr. de Young's watchful eye, are able to bring home a salary, however small, and they and the place glow.