First; this study answered very important questions regarding creatine uptake into brain, and documented pharmacologic dosing levels. This is important because brain penetration is absolutely necessary for any (successful) Huntington’s drug. It can be argued that this type of drug/brain penetration testing should be required of any drug candidate prior to entering expensive phase III trials in Huntington’s.

Second; the authors used MRS, a radiologic technique reviewed previously at Lighthouse, ( NAA - biomarker for HD?) to measure creatine brain levels. MRS technique may prove useful as a sensitive measure of disease progression in the future. And sensitive measures of progression will shorten the time needed for clinical trials.

Third, they reported increased levels of 8OH2dG in the blood of Huntington’s people that was decreased with creatine use. Earlier reports had described elevation of this chemical in blood, urine and brain tissue of Huntington’s mice. This chemical is a measure of DNA oxidative injury, and is elevated in other neurodegenerative diseases as well. The authors showed that creatine decreased the level of this marker in Huntington’s people, suggesting that creatine also decreased oxidative injury. They further speculate that 8OH2dG is a promising biomarker for studying drug response in HD.

This is a scientifically elegant study with many practical (and promising) results for HD people. This is the kind of trial we’d like to see more of.

-- LaVonne Veatch Goodman, M.D.

 

Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG.

Authors: S. M. Hersch, MD, PhD, S. Gevorkian, MSc, K. Marder, MD, MPH, C. Moskowitz, MS, A. Feigin, MD, M. Cox, MS, RN, P. Como, PhD, C. Zimmerman, RN, M. Lin, MD, L. Zhang, MD, A. M. Ulug, PhD, M. F. Beal, MD, W. Matson, PhD, M. Bogdanov, E. Ebbel, A. Zaleta, BA, Y. Kaneko, BA, B. Jenkins, PhD, N. Hevelone, MPH, H. Zhang, MS, H. Yu, MPH, D. Schoenfeld, PhD, R. Ferrante, PhD, MSc and H. D. Rosas, MD, MS

The Journal Abstract

In a randomized, double-blind, placebo-controlled study in 64 subjects with Huntington disease (HD), 8 g/day of creatine administered for 16 weeks was well tolerated and safe. Serum and brain creatine concentrations increased in the creatine-treated group and returned to baseline after washout. Serum 8-hydroxy-2'-deoxyguanosine (8OH2'dG) levels, an indicator of oxidative injury to DNA, were markedly elevated in HD and reduced by creatine treatment.

The Press Release: Avicena's HD-02 Demonstrates Potential In Treatment Of Huntington's Disease

Study Shows Compound is Safe, Well-Tolerated and May Reduce Oxidative Injury

Avicena Group, Inc., a developer of novel pharmaceutical and therapeutic products, announced today that findings from a Phase I/II study of its proprietary drug candidate for the treatment of Huntington's disease (HD-02) demonstrated that the drug was safe and well-tolerated by patients at a dose of eight grams/day. Additionally, patients receiving HD-02 experienced elevated serum and brain levels of creatine. Results from this study, which was supported by the National Center for Complementary and Alternative Medicine (NIH/NCCAM), were published today in the journal Neurology.

Additional findings from the trial showed that serum 8-hydroxy-2'-deoxyguanosine (serum 8OH2'dG) levels, which are markedly elevated in Huntington's disease patients, were reduced for patients receiving HD-02. Some researchers believe that this decrease in serum 8OH2'dG may suggest reduced oxidative injury in patients with Huntington's disease.

"We are very encouraged by the outcome of this important study. Not only did our data show that HD-02 is safe and well-tolerated, but we were also able to collect compelling evidence to indicate that the compound may reduce oxidative injury in patients with Huntington's disease," stated Steven Hersch, M.D., Ph.D., director, Laboratory of Neurodegeneration and Neurotherapeutics, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Harvard Medical School and the study's lead investigator. "This study's findings clearly support the further evaluation of HD-02 as a potential neuroprotective treatment for Huntington's disease."

HD-02 is a proprietary therapeutic that incorporates an ultra-pure, clinical form of creatine that has demonstrated the ability to improve neurological function in certain patient populations. The 64 patients enrolled in this multi-site, double-blind, placebo-controlled trial were randomized to receive either eight grams of HD-02 or placebo each day for 16 weeks. The treatment period was followed by an eight week washout period. Following the washout period, elevated serum and brain creatine concentrations returned to pre-treatment levels for patients receiving HD-02.

The study's investigators intend to use the findings from this trial to design late-stage studies of HD-02 aimed at examining the drugs' ability to slow or halt the progression of Huntington's disease. Dr. Hersch, NIH/NCCAM, and Avicena are currently examining higher doses of the compound in a dose-escalation study, as well as a Phase II open-label trial.

"We are very pleased with the data from this study, as these findings will allow us to optimally design the upcoming studies in our Huntington's disease program," said Belinda Tsao-Nivaggioli, Ph.D., Avicena's chief executive officer. "Our continued clinical success with regard to our Huntington's disease compound, as well as our late-stage ALS and Parkinson's disease programs, place Avicena in the position of having multiple drug candidates advancing rapidly through clinical development."

Source: Neurology 2006 Jan 24;66(2):250-2