SCA6
Research has shown that SCA6 is caused by an abnormal CAG repeat in a gene called CACNA1A which codes for a specific calcium channel subunit (the alpha 1A subunit of the voltage dependent P/Q type calcium channel), which is found at particularly high levels in the cerebellum (Baloh & Jen, 2000; Zhuchenko et al, 1997). Calcium channels are found in the outer layer of the cell, known as the cell membrane, where they are critical in controlling the chemical balance in nerve cells which is crucial for many cell processes. It is thought that in SCA6, an abnormality affecting the function of the calcium channel in turn affects the essential functions of the cell. This type of disorder is known as a channelopathy.
It is believed that SCA6 mutations cause short-term periods of inactivation of the calcium channels, which correspond to ataxic episodes. The mutations are also thought to result in longer-term excess amounts of calcium in the cell that are toxic and lead eventually, to cell death (Baloh & Jen, 2000).
The number of repeats in SCA6 seems to be relatively stable and remains constant as it is passed down the generations (Baloh & Jen, 2000). There is however, a large amount of variability in the clinical symptoms associated with the condition. The CACNA1A gene is also associated with episodic ataxia type 2 (EA2) and a migraine disorder (familial hemiplegic migraine) and in some families, these related disorders appear to overlap (Jen et al, 1998).
Research into possible treatments for SCA6 focuses on regulating the function of ion channels. Some individuals with SCA6 have responded to treatment with acetazolamide (Jen et al, 1998). This is a carbonic anhydrase inhibitor thought to alter the pH around calcium channels and make them more stable. It is currently used in the treatment of EA2. Ataxia UK has funded research in Sheffield, led by Dr Weiss, looking at proteins involved in the channel regulation pathways that could be potential targets for treatment. Click here for details.
REFERENCES
Baloh & Jen 2000. Episodic Atxia Type 2 and Spinocerebellar Ataxia Type 6. In Klockgether (ed), Handbook of Ataxia disorders, New York; Marcel Dekker, p.447-468.
Jen et al. J Neurol Neurosurg Psychiatry, 1998; 65(4): 565-568
Zhuchenko et al. Nat Genet, 1997; 15(1): 62-69
Page created February 2012
