Mutations in the superoxide dismutase (SOD1) gene are the second most common cause of inherited ALS, and account for approximately 2% of ALS cases. Antisense oligonucleotides designed to reduce levels of SOD1 represent a promising therapeutic approach that has already proven safe in Phase I clinical trials (see May 2013 news). However, in order to determine the treatment regimen most likely to be effective in humans, characterization of the kinetic properties of SOD1 is essential. A new study led by Timothy Miller and Randall Bateman from Washington University in Saint Louis, Missouri and published in the June 15 Journal of Clinical Investigation determined the turnover rates of SOD1 in the CSF and CNS of rats expressing human SOD1, as well as in healthy humans. These findings are an important step in advancing the SOD1 antisense clinical trial, as well as other trials for therapies targeting SOD1 expression.
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Crisp MJ, Mawuenyega KG, Patterson BW, Reddy NC, Chott R, Self WK, Weihl CC, Jockel-Balsarotti J, Varadhachary AS, Bucelli RC, Yarasheski KE,Bateman RJ, Miller TM. In vivo kinetic approach reveals slow SOD1 turnover in the CNS. J Clin Invest. 2015 Jun 15. [PubMed].