Wagner and coworkers used myotube ATP levels to screen for induction or prevention of myopathy caused by statins. They found that statins decreased ATP levels, but addition of geranylgeranyl pyrophosphate (GGPP) restored ATP levels caused by statins, indicating a role for protein prenylation in causation of myopathy. Additionally, they found that inhibition of GGT-II decreased ATP levels, indicating that Rab prenylation is being blocked. They screened a library of compounds and found 4 that restored ATP levels when co-administered with statins. Inhhibition of GGII blocked the rescue caused by those four compounds. Finally, one of the compounds was tested with a statin in zebrafish and was found to reduce myopathy.
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