Advances in genetic knowledge have transformed our understanding of disease in recent years. We now know which genes are linked to a wide variety of conditions. However, so far, very few cures and treatments have developed as a result of this knowledge.

Now a UK study led by researchers at Cardiff University suggests that a chemical first found on Easter Island could treat the genetic disorder tuberous sclerosis.

Tuberous sclerosis is an inherited disease affecting children and adults which causes tumours to grow in many of the organs of the body. Its consequences can include autism and epilepsy through its effects on the brain. A team from the Institute of Medical Genetics at Cardiff University's School of Medicine was the first to identify the genes linked with the disease “ TSC1 and TSC2.

The Institute is now leading a UK-wide study on a new treatment involving the drug Sirolimus. This was first identified from a soil sample taken from Easter Island and has been shown in the past to control the activity of a protein, mTOR, which is normally controlled by the TSC1 and TSC2 genes. If the genes fail, mTOR is too active leading to tuberous sclerosis.

The UK study tested the effects of Sirolimus on kidney tumours in patients with tuberous sclerosis and a related condition, LAM, a lung and kidney disease affecting young women. The study is at the half-way stage but after one year of treatment the diameters of the tumours have shrunk by an average of 26 per cent. A parallel study in the United States has also reported similar results.

Professor Julian Sampson, director of the Institute of Medical Genetics, said: This is a small-scale study and we will be treating patients for a further year before it is completed. However, what we have seen so far is very promising and already justifies progression to a larger study in many more patients. The findings offer new hope for what is a very serious and distressing genetic disease.

cardiff.ac/

The results of the investigation are now published in the December edition of the specialised magazine Medical Oncology (Position-dependent expression of GADD45alpha in rat brain tumours. Br A, Del Fresno C, Soares-Schanoski A, Albertos S, Br I, Porres A, Roll n-Landeras E, Dopazo A, Casero D, G mez-Pi?±a V, Garc?­a L, Arnalich F, Alvarez R, Rodr?­guez-Rojas A, Fuentes-Prior P, L pez-Collazo E. Med Oncol. 2007;24 (4):436-44). Among the conclusions reached, the most relevant comes from the difference in the nuclear protein GADD45a, which regulates the cellular response to DNA damage and stress signals. This protein is expressed in many normal tissues, particularly in cells in a quiescent state (G0 phase of the cell cycle). The concentration of GADD45a increases during G1 phase of the cell cycle and greatly decreases when the cell is at S phase, demonstrating its crucial role in the response function to many stress or genotoxic signals. This protein has also been related to the programmed cell-death, the survival of cells and their innate immunity. In particular, it has been demonstrated that it inhibits cyclin B/CDC2, which constitutes a protein complex that controls the transition G2/M in the cellular cycle.

According to the conclusions, this protein is expressed in much higher levels at the boundary than at the inside of solid tumours. This gives GADD45a a more important role in the evolution of the tumour and its invasive capability. The control of this cellular apoptosis regulator at the tumour expansion boundary is predicted by the universal dynamics of tumour growth elaborated by Dr. Br and his team over the last few years. These results allow for a better understanding of the genetic and phenotypic evolution that are currently explained in different theories of evolution as well as relating it to the growth dynamics of the tumour.

rect.ucm.es/