They are cheerful children with quite normal childlike needs and desires – but their lifespan is frighteningly short. As if in fast motion, they age, the childlike oldsters; most of them do not reach their 15th year already. Thanks to human genome research, a first breakthrough has been made in terms of cause and therapy. Fortunately, Hutchinson-Gilford syndrome (HGS), also known as progeria, is a very rare disease. Worldwide, estimates are that there are around 50 patients, and in Germany there are about six children.
Progeria: premature senescence
Progeria comes from Latin and Greek and means “premature senescence.” Affected individuals suffer from, among other things:
- Growth disorders
- Rapid aging of the skin
- Bone loss
- Arteriosclerosis
- Hair loss
- Joint changes.
Heart disease or strokes lead to early death. Very rare diseases like these are being researched, but funds are limited, not least because of the large discrepancy between effort and return for pharmaceutical companies. In the case of HGS, a very first glimmer of hope is emerging, albeit a small one.
HGS: The cause is a genetic defect
Researchers had discovered in 2003 that progeria appears to be due to a single mutation in the laminin gene on chromosome 1. The consequence of the mutation: the tissue can no longer regenerate. To put it simply, laminins are proteins. They are of crucial importance in the construction of the cell nuclear envelope. Dr. Francis S. Collins, the director of the American Human Genome Research Institute in Bethesda, Maryland (USA), together with scientists from the Progeria Research Foundation, reported what happens during the mutation: A single “spelling mistake” in the lamin A gene (LMNA) is responsible. Lamin-A is the key component of the membrane that surrounds the cell nucleus. The researchers found that 18 of 20 children with progeria all have the same spelling mistake in the lamin-A gene: the base cytosine is swapped with the base thymine. The altered protein is called progerin. To understand, in DNA – on which all hereditary information is stored – the four bases adenine, cytosine, guanine and thymine occur, and when they are “arranged” correctly, cells develop normally.
Hope is offered by a cancer drug
This discovery and knowledge of the gene defect in Progeria set the stage for a crucial discovery related to a cancer drug still in testing. As the journal Science reported on February 16, 2006, the drug FTI (farnesyltransferase inhibitor) is seen as a hopeful candidate in the treatment of various cancers such as leukemia. It interferes with signal transduction pathways and enzyme activities and prevents the stimulation of cell division typical of cancer. The active ingredient FTI may also be effective in progeria. In laboratory experiments with mice at the University of California at Los Angeles (UCLA), the small rodents suffering from progeria were given FTI. The RTIs were instrumental in blocking an enzyme – with the result that the faulty progerin molecules were not incorporated into the nuclear membrane in the first place. Instead, they accumulated in the nucleus, where they did much less damage, according to the scientists. After treatment with RTI, most of the mice showed a significant improvement in, for example, body weight, bone stability compared to a control group. However, the disease was not completely cured.
Progeria and genetic research
The steps that genetic research takes are small. It sometimes takes many years to achieve a breakthrough. The discussion about ethical responsibility, what is feasible and what is justifiable takes on a human dimension in the face of such diseases as progeria. Much education will still be needed. But the fact is: the comprehensive analysis of the DNA sequence is aimed at understanding the human organism. “The genetic makeup of humans is the starting point for recognizing and treating the causes of disease. It is expected that the Human Genome Project will find genetic changes in the complex of origins of about 10,000 diseases.” – according to the German Human Genome Project.This initiative, funded by the German Federal Ministry of Education and Research and the German Research Foundation, aims to systematically identify and characterize the structure, function, and regulation of human genes, especially those of medical relevance.
