Hoping to cure a cruel childhood illness - Maria Eriksson

The name for this cruel and very rare disease is progeria. It is caused by an unusual mutation, a change in the genetic material affecting cell construction. Maria Eriksson and her research group at Novum are working to study this mutation and its consequences.

"An important goal is to increase understanding of the disease and thereby our chances of helping child sufferers. There are currently no remedies, and we're hoping to contribute to the possibility of one day producing a treatment," says Maria Eriksson.

Another goal is to be able to study ageing on a more general level by investigating cell mechanisms and biological processes in premature ageing. Why do many people in certain families live to over 95? Which genes and mechanisms control how we age and how old we get?

Maria Eriksson's doctorate at the Karolinska Institute was in the field of neurogenetics and she has since completed her post-doc training at the National Human Genome Research Institute in Maryland, USA. She wanted to run her own project and was offered the chance to try and find out which mutation causes progeria, or Hutchinson-Gilford Progeria Syndrome to give it its full name.

For an extremely rare disease like progeria, with around 100 known cases since its discovery at the end of the Nineteenth Century and currently between 30 and 40 cases worldwide, it is very hard to find the genetic error. A number of the methods used for genetic studies of more common diseases are quite simply unusable as there are so few cases. Nevertheless, Maria took on the challenge.

"I guess I was naïve," she smiles.

Using the available material in the form of cells from patients, she and her colleagues started searching. They found abnormalities in cells from three patients, indicating a change in a certain area of Chromosome 1. The researchers decided to look more closely at the 80 genes in this area to see if the disease-causing mutation was present in any of them. They started with a gene that was a little more suspect. This was partly because other researchers studying a family with a disease resembling progeria had found mutations in this gene. And in this very gene, the first one they analysed, Maria Eriksson and co-workers found the mutation behind progeria.

Their discovery in 2003 created a stir in the research world and offered a glimmer of hope to child sufferers and their families. Knowing about the mutation opens opportunities for finding out which substances in the cells are abnormal in progeria, as well as which mechanisms in the cells and bodily processes are affected and how. This may be the first step on the way to developing substances to combat the morbid changes.

In progeria the mutation, the predisposition to the disease, is dominant. This means that a predisposition from one parent is sufficient for the disease to develop. This disease only appears in children, not in their parents. Thus it is not a hereditary disease. Rather, it is probably true that the mutation occurs in a single sperm or egg prior to conception.

The mutated gene is called LMNA and comprises the blueprint for a protein called lamin A. This protein plays an important role in the construction of the network inside the cell nucleus which supports the nuclear structure. When the gene mutates, the protein becomes abnormal and the patient's cell nuclei take on an abnormal form.

Discovery of the mutation made it possible to start creating animal models to study progeria and ageing. Maria continued with this work when she returned to Sweden after her post-doc stay and started building up her research group at Novum. The models have the human mutation and are designed so that the mutation can be "turned on" and "turned off" in various tissues. Thus it is possible to study the effects of the mutation in one organ at a time. For example, the research group has produced a well-functioning model to study how the mutation affects the skin. The skeleton, blood vessels and other organs can then be studied in the same way, which may be of particular interest when investigating prominent processes in both premature and normal ageing.

"The mutation produces accelerated ageing which is however thought to be otherwise similar to natural ageing. This enables us to research into both the rare disease of progeria and very common age-related endemic diseases such as stroke, heart attack and brittle bones."