HD Australia

http://www.hdlighthouse.org/showUpdate. ... Number=664


HD Lighthouse Contributing Editor's Comment:

CHDIscientists and their colleagues at Psychogenics have conducted arigorous mouse study and found that neither CoQ10 nor minocycline werehelpful in the R6/2 mouse and that high doses of minocycline resultedin decreased survival time.

CHDI contracted with Psychogenicsto carry out studies of promising compounds in mouse models ofHuntington's Disease, including compounds that had already beenreported as helpful.  The mice are housed in better conditions withbetter and more accessible food.   The studies involve larger numbersof mice, matched control and experimental groups, semi-randomlyselected, assessment on several behavioral measures, and real ratherthan estimated survival time data.

CoQ10 had been previouslyreported as helpful in a mouse model of HD.  A Phase III clinical trialwhich ended in 2001 found a modest trend in slowing disease progressionbut it did not reach statistical significance.  The rationale behindthe interest in CoQ10 is that it may boost cellular energy, known to beimpaired in Huntington's Disease and it is an antioxidant.  Oxidativestress is also believed to be a problem in the disease.

Whataccounts for the difference between the findings in this study andprevious studies?  Why did a promising compound fail to help the mice? There are a number of possibilities.   One likely possibility concernsbioavailability.   CoQ10 has poor bioavailability in the brain and itmay be that sufficient levels weren't achieved in the brain.   On theother hand, supplementation can help raise levels in the brain if theyare too low because of poor nutrition.  If the mice in the previousstudies were nutritionally deprived as compared to those in the currentstudy, this may explain why supplementation did help them.   Thequestion of whether an analogue of CoQ10 with better bioavailabilitymight help the HD mice and  Huntington's patients is still an openquestion.  

Another possibility is that the enriched housingaddresses the energy deficiency to the extent that CoQ10 cannot addadditional effects.

Studies with minocycline have had mixedresults.  Some studies with the R6/2 mice found it to be helpful butothers did not.  Minocycline did not help the N171-82Q model andactually was toxic in the 3NP mouse model.  A clinical trial of higherdose minocycline in ALS patients found that the minocycline group diedsooner than those in the treatment group but a lower dose trial in HDpatients found no safety issues although the results did not warrantpursuing it as a treatment.

The initial interest in monoclinewas because it was hoped that it would prevent apoptosis, programmedcell death.  Later researchers were interested in the antibiotic'spossible effect on neuroinflammation, free radical damage,excitotoxicity, and aggregation.
In this study, a small dosewas injected in one experimental group and two higher doses wereadministered in food to two additional experimental groups.   In thefirst group, there were statisticalyl significant improvements in bodyweight and two behavioral measures; however they did not persist andthere was no improvement in survival time.
In the higher dose groups, no improvements were found and survival time was decreased.

Theauthors also note that there is a publishing bias in that studies withgood results are more likely to be published than studies that find adrug or supplement to be ineffective.  The standard of statisticalsignificance is that it should be no more likely than one in twentythat the results are due just to chance rather than being meaningful. If twenty studies of possible treatments are carried out, the chancesare good that that one of them might have a statistically significantresult just due to random differences between the two groups ratherthan treatment effects.  If disappointing results are not made publiclyavailable, we won't know if something has been tried before and itexaggerates the importance of achieving one.   The authors call for apublic forum to make the results of all these studies known regardlessof whether an academic journal has an interest in publishing them
Giventhe results of the study, people with HD taking CoQ10 may want toreconsider and wait until there are results from additional studies.  Given previous reports on minocycline, people with HD who were takingminocycline hoping it might be a treatment should have talked to theirdoctor about discontinuing it.

-- Marsha L. Miller, Ph.D.

Posted to the HDL:
04-14-2010