In a paper published this week in the prestigious journal Nature, Dr. Solomon Snyder and colleagues reported promising results in cell and mouse models of Huntington's disease (HD). They showed that these models were deficient in both (1) cysteine, one of the amino acid building blocks in proteins, and (2) an enzyme molecule involved in making cysteine. And more exciting, they showed that adding cysteine was protective in these models.

Might cysteine help people with Huntington's disease? Preliminary results reported in Raptor Pharmaceutical's recent press release suggests it may.

The Snyder Laboratory results: In addition to other elegant experiments looking at the molecular biology involved, the scientists in this lab showed that when cysteine was added to the nutrient medium of HD model cells, cell function normalized almost completely. Next, they gave cystine (a molecule that contains two cysteines) in food and N-acytyl cysteine, (a cysteine-related molecule) in drinking water to a mouse model for HD. Results included improvement in motor function measures, preservation of brain size, and increase in lifespan. A summary of this extensive work was presented in a poster at the March 2014 CHDI Therapeutics Conference. The article can be accessed on PubMed [Paul BD 2014].

The degree of mouse model benefit shown in the Snyder lab corresponds very closely to the results from Karpuj and colleagues [Karpuj MV 2002] almost a decade ago where cystamine (another molecule similar to cysteine) was given. Those results were confirmed in other labs and mouse models of HD [Dedeoglu A 2002, Van Raamsdonk JM 2005].

What about People with HD? Using postmortem brain samples from individuals with HD, the Snyder lab showed that cysteine is deficient in HD people too, and the degree of deficiency worsened with disease stage. Combining their animal model and human brain study, the Snyder lab results suggest that cysteine supplementation may be a useful treatment for individuals with HD. Further human data from an ongoing clinical trial of Raptor Pharmaceutical's cysteamine drug (another molecule similar to cysteine) showed that significant slowing of motor dysfunction occurred for those participants who received drug compared to placebo. Though not yet peer reviewed for publication, the results appear optimistic.

Author's comments: Though it is unclear (at least for this author) which molecule cited from different labs: cysteine, cysteamine, cystine, or cystamine is the active agent; or more likely, that the latter three molecules simply result in increase in brain cysteine levels [Fox JH 2004]. In another study, authors suggest the active compound is cysteamine, the same molecule used in the Raptor trial [Bousquet M 2010]. We look forward to more human study results from Raptor at completion of their present trial. Though I suspect they are already talking with regulatory agencies, there will likely be need for another confirmatory clinical trial.

Now the hard questions become: is there an argument for taking an OTC USP-approved cysteine-like supplement? The answer is probably "not yet". Though cysteine and N-acetyl cysteine are available as supplements, human dosage isn't known. It would be like treating hypothyroidism by guessing at the dose of thyroid medication; too little isn't very helpful, and too much is harmful. Probably best to wait for a little more information from human study in clinical trial, and to be very thankful that Raptor is doing just that.


Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH. Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington's disease. Nature. 2014 May 1;509(7498):96-100. doi: 10.1038/nature13136. Epub 2014 Mar 26. PubMed abstract

Karpuj MV, Becher MW, Springer JE, Chabas D, Youssef S, Pedotti R, Mitchell D, Steinman L. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med. 2002 Feb;8(2):143-9. PubMed abstract

Dedeoglu A, Kubilus JK, Jeitner TM, Matson SA, Bogdanov M, Kowall NW, Matson WR, Cooper AJ, Ratan RR, Beal MF, Hersch SM, Ferrante RJ. Therapeutic effects of cystamine in a murine model of Huntington's disease. J Neurosci. 2002 Oct 15;22(20):8942-50. PubMed abstract

Van Raamsdonk JM, Pearson J, Bailey CD, Rogers DA, Johnson GV, Hayden MR, Leavitt BR. Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease. J Neurochem. 2005 Oct;95(1):210-20. PubMed abstract

Fox JH, Barber DS, Singh B, Zucker B, Swindell MK, Norflus F, Buzescu R, Chopra R, Ferrante RJ, Kazantsev A, Hersch SM. Cystamine increases L-cysteine levels in Huntington's disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation. J Neurochem. 2004 Oct;91(2):413-22. PubMed abstract

Bousquet M, Gibrat C, Ouellet M, Rouillard C, Calon F, Cicchetti F. Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases. J Neurochem. 2010 Sep;114(6):1651-8. doi: 10.1111/j.1471-4159.2010.06874.x. Epub 2010 Aug 19. PubMed abstract