Biomedical Updates


Creatine Thwarts Huntington’s Disease

M assachusetts General Hospital, perhaps the greatest diagnostic center in the U.S. if not the world, has found a benefit for creatine in delaying the symptoms of the inherited neurodegenerative disorder known as Huntington disease.1 The disease is caused by a mutation of a gene that expresses the huntingtin protein that interferes with energy production, depleting adenosine triphosphate (ATP) and damaging the brain.

“A variety of age-related diseases, such as neurodegenerative conditions (including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis), are associated with aggregation of proteins due to improper folding. Other conditions (known as “conformational diseases”) associated with improperly folded proteins include cancer, cystic fibrosis, emphysema, liver disease, prion disease (such as mad cow) and even chronic pain (opioid receptors misfolded in the endoplasmic reticulum).”2 (Emphasis added, reference removed.)

While the role of creatine for Huntington’s disease is not new and in fact was reported as early as 2003,3 the new trial was preventative. It involved 64 eligible participants who were randomly allocated to two groups, one taking 15 g twice daily of creatine monohydrate or placebo for a 6-month double-blind phase followed by a 12-month open-label extension. Subjects were either predisposed by test or untested individuals (but predisposed by heredity) without clinical symptoms or signs of Huntington’s disease.

For the double-blinded portion of the trial in which half of the participants received a placebo and the rest received 15 to 30 grams creatine per day for six months. This was followed by a 12-month open-label period in which some of the participants who received a placebo were switched to creatine.

At the end of the placebo-controlled phase of the trial, degeneration in the brain’s cortex and striatum among Huntington disease carriers, as determined by MRI, was slower among those who received creatine than among the placebo group, who experienced progression. This benefit was also observed among presymptomatic subjects who began creatine supplementation after the placebo-controlled phase. Creatine was found to be safe and well-tolerated by the majority of those who received it.

The results demonstrate the likelihood that prevention trials for Huntington’s disease and the safety of high-dose creatine, provide evidence of disease modification.

References

  1. Rosas HD, Doros G, Gevorkian S, Malarick K, Reuter M, Coutu JP, Triggs TD, Wilkens PJ, Matson W, Salat DH, Hersch SM. PRECREST: A phase II prevention and biomarker trial of creatine in at-risk Huntington disease. Neurology. 2014 Feb 7. [Epub ahead of print]
  2. Papp E, Csermely P. Chemical chaperones: mechanisms of action and potential use. Handb Exp Pharmacol. 2006;172:405-16.

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