SCA7
SCA7 is usually associated with progressive macular degeneration (Stevanin et al, 2000). This is damage to a part of the eye known as the retina and usually results in blindness in the centre of the visual field.
SCA7 is caused by an abnormal CAG repeat in the ataxin-7 gene (David et al 1997). This gene codes for the protein ataxin-7. The function of this protein in not fully understood but is thought to have a role in the regulation of gene transcription (the production of proteins from the genetic code in DNA) (Helmlinger et al 2004, Taylor et al, 2006).
The greater the number of CAG repeats the more severe the condition and the earlier the symptoms begin to show. In SCA7, the number of CAG repeats often expands when the gene is passed from a parent, particularly fathers, to their children. This is known as anticipation and results in an increasingly severe form of SCA7 in each generation. However SCA7 can also arise from spontaneous mutations in the gene without any prior history in the family (Stevanin et al, 1998).
Researchers in Paris have developed a fly model of SCA7 which displays similar protein aggregations to those seen in humans with SCA7 (Latouche et al, 2007). This is being used to try and understand more about the condition and what possible treatments are effective.
Another group of researchers (Young at al 2007) has suggested that enzymes involved in cell death (apoptotic enzymes) called caspases may play a role in SCA7. They were found to break the mutated ataxin-7 protein up into fragments that are toxic to the cell. These fragments may contribute to cell degeneration and therefore represent another potential target for treatment.
A research team at the University of Oxford, led by Dr Matthew Wood, received funding from Ataxia UK to investigate RNA interference therapy for SCA7. RNA is the intermediate message from a gene that is translated into a protein by the cell’s protein making machinery. The theory with Dr Wood’s research is that interfering with the RNA message from the faulty gene can reduce levels of toxic protein in cells. The researchers have succeeded in finding ‘silencing’ pieces of RNA which discriminate against the protein that is mutated in SCA7 and block its message. They have now identified a compound which appears to be safe enough for us to take forward for tests in cells from patients and animal models.
Read more about Dr Wood’s research project
REFERENCES
David et al. Nat Genet, 1997; 17(1): 65-70
Helmlinger et al. Hum Mol Genet, 2004; 13(12): 1257-1265
Latouche et al. J Neurosci, 2007; 27(10): 2483-2492
Stevanin et al. Hum Mol Genet,1998; 7(11): 1809-1813
Stevanin et al, 2000, Spinocerebellar Ataxia Type 7. In Klockgether (ed), Handbook of Ataxia disorders, New York; Marcel Dekker, p.469-486.
Taylor et al. J Biol Chem, 2006; 281(5): 2730-2739
Young et al. J Biol Chem, 2007; 282(41): 30150-30160
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