MGH/Harvard drug treats Huntington's in 2 mouse studies

Massachusetts General Hospital/Harvard scientists have developed a new drug candidate that appears to successfully reduce and protect against Huntington's disease damage in two mouse studies. Its target: blocking the activity of SIRT2, an enzyme that regulates a number of cellular functions.

Both mouse studies involved twice-daily injections of AK-7, a SIRT2 inhibitor that is brain-permeable. The mouse groups had two different variations of Huntington's disease, one with rapid progression and really bad neurological symptoms, and the other, a genetically similar version to human Huntington's disease that was also fairly aggressive.

Both studies involved injections of AK-7 twice daily at three different dose levels beginning at four weeks and culminating at 14 weeks. Both studies improved motor function in the mice, lessened neurological damage and lengthened life spans. But the mouse study with the genetic variation closer to human Huntington's disease--the 140 CAG Htt knock-in model--helped maintain normal motor activity compared with untreated mice with the condition, all of which faced a rapid decline. These mice also had major improvements in brain function, according to the study.

This is obviously early work here, but the results help narrow the focus for subsequent drug development work and show the potential of SIRT2 inhibitors to treat Huntington's. Existing drugs don't slow Huntington's progression, but the researchers argue that their work shows that stronger SIRT2 inhibitors could lead to drugs that hold back rapid progression of the neurodegenerative disease. They plan on testing stronger SIRT2 inhibitors in future Huntington's mouse trials to further test their theory. The treatment may be a long way from human trials, but the preclinical testing goes forward.

For details, read the journal Cell Reports.

- read the release
- here's the journal summary