N -Acetylcysteine for Huntington’s?

To the Editor

Huntington’s disease is a progressive uniformly fatal autosomal dominant disorder associated with neuroprogressive features in the corpus striatum that have been linked to oxidative stress and mitochondrial dysfunction – eventuating in motor and behavioural changes. No evidence-based therapies exist. Recently, a major depletion of cystathionine c-lyase (CSE) in Huntington’s disease, which is the biosynthetic enzyme for cysteine, has been described (Paul et al., 2014). CSE generates cysteine from cystathionine and critically, in intact mouse models of Huntington’s disease, supplementation of cysteine via its precursor, N-Acetylcysteine (NAC), was found to delay motor symptoms. This is in keeping with NAC reducing oxidative stress and mitochondrial dysfunction in multiple preclinical models, including models of Huntington’s disease (Sandhir et al., 2012; Wright et al., 2015); however, there are no human studies.

XC is a 54-year-old married lady first seen in 2012 who previously worked as a division 2 nurse. Her mother died at the age of 56 of Huntington’s disease. She has a brother and a sister neither of whom have symptoms nor have ever been genetically tested for Huntington’s chorea. XC tested positive for Huntington’s in 2003 but regrets the decision because it proved to be a burden for her over ensuing years. Her symptoms started approximately 10 years ago with subtle movements in her hand. Her movements increased over the years and now interfere with her life. She can still shower, but her husband has had to take on many activities, including cutting her nails and cooking. According to both her and her husband, her memory for day-to-day things is not great. The principal reason for psychiatric referral was depression, having struggled with depression and anxiety ‘all my life’, which worsened with onset of Huntington’s. Her current treatment included Zoloft 100 mg daily, Haloperidol 0.5 mg daily, Tetrabenazine 2 at night, and oxybutynin. Medically, she had undergone a cholecystectomy, suffered from vitiligo and had an L5, S1 disc prolapse some years ago. In light of the abovementioned reports showing that NAC had potential efficacy in preclinical models of Huntington’s disease, supported by the emerging data on the safety and utility of NAC in diverse neuropsychiatric disorders, oral NAC was commenced in March 2014 at a daily dose of 2 g. Unified Huntington’s Disease Rating Scale (UHDRS) scores were assessed over a 1-year period and her serial scores were 84 (31 March 2014), 86 (21 July 2014), 88 (6 October 2014), and 79 (20 July 2015), suggesting no significant shift in core features of her illness; however, she had a marked improvement in mood and subjective quality of life. Further studies involving asymptomatic, at-risk individuals are perhaps warranted.