HD Lighthouse Contributing Editor's Comment: This study of minocycline in the N171-82Q mice is the latest research in the controversy over minocycline as a potential treatment for Huntington's Disease.

The researchers administered 10 mgs/kg of minocycline daily but observed no benefit over the untreated HD mice. The minocycline did cross the blood brain barrier and did inhibit the expression of caspase 1 which plays an important role in apoptosis (programmed cell death). However, the minocycline-treated mice did not survive longer or perform better on motor tests and did not experience less weight loss or less neuropathology compared to the untreated mice.

In contrast, a study of the minocycline alone and in combination with CoQ10 in the R6/2 mice did yield positive results. See our update here: HDL: A milestone: combined treatment of minocycline and CoQ10 helped the R6/2 mice

For a 2004 review of the evidence on minocycline, go here: Huntington Project: Minocycline (pdf)

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 22 Dec 2006

Lack of Minocycline Efficiency in Genetic Models of Huntington's Disease.

Stéphane, Mievis; Marc, Levivier; David, Communi; Gilbert, Vassart; Jacques, Brotchi; Catherine, Ledent; David, Blum

According to the recent controversy regarding the effects of minocycline in the R6/2 transgenic model of Huntington’s disease (HD), this tetracycline has been re-evaluated in another model, the N171-82Q strain. Ten miligrams per kilogram minocycline was given daily from the age of 2 mo, corresponding to an early symptomatic stage. We did not observe improvement in survival, weight loss, or motor function in treated transgenic mice. In addition, minocycline failed to mitigate the ventricle enlargement as well as the striatal and cortical atrophies induced by the transgene. Using high-performance liquid chromatography, it was observed that minocycline was similarly present in the plasma and the brain of both wild-type and N171-82Q mice following 14 daily injections. Using Western blot, we show that the increased expression of procaspase-1 induced by the transgene in the cortex was significantly reduced by the antibiotic. Combining together these data support that despite minocycline crosses blood–brain barrier in N171-82Q mice and displays an expected effect on procaspase-1 expression, it does not provide protection in this HD model. These in vivo results are in accordance with in vitro data, since minocycline failed to protect against mutated Huntingtin in an inducible PC12-clone expressing exon1 of mutated Huntingtin103Q. Altogether, the present data does not support minocycline as a beneficial drug for HD. # # #

Source: NeuroMolecular Medicine February 2007, Volume 9, Issue 1, pps. 47-54

printer friendly version

 

	Read the HDAC/HDLighthouse Forum. Post your comments