Journal of Psychopharmacology 17(4) (2003) 461
2003 British Association for Psychopharmacology (ISSN 0269-8811)
Letter to the Editors
Why minocycline is helpful in Huntington’s disease
Raphael M. Bonelli and Hans-Peter Kapfhammer
University Clinic of Psychiatry, Karl-Franzens University Graz, Austria.
We would like to congratulate Denovan-Wright and colleagues for
brain able to restore function even with the toxic pathways being
their important observation (Denovan-Wright et al.
, 2002) in a
blocked? The recent findings may lead in this direction.
recent issue of the Journal of Psychopharmacology
. They treated a
Ona et al.
(1999) and Chen et al.
(2000) started minocycline ‘in
patient with advanced Huntington’s disease (HD) with minocycline
the late presymptomatic stage’ of transgenic HD mice. It would be
for more than 1 year and observed positive effects. They suggest
interesting to repeat their trials in a symptomatic stage to
that minocycline may be of benefit in those patients with advanced
investigate a possible duplication of the effects observed by
HD and can be used safely in these patients.
Yamamoto et al.
(2000), which would be clinically more relevant.
We ourselves found a similar improvement of motor function in
A double-blind, placebo-controlled trial appears highly warranted
10 out of 14 patients and an amelioration of cognitive function in
to definitively establish the value of minocycline in HD.
seven out of 14 HD patients with minocycline after 6 months onthe drug (Bonelli et al
., 2003) and underline their conclusions. Weobserved these ameliorative effects in all HD stages, not only in the
advanced group, as suggested by Denovan-Wright and colleagues,and so would extend their suggestion to all symptomatic HD
patients. Ona et al.
(1999) previously demonstrated evidence of
University Clinic of PsychiatryKarl-Franzens University Graz
caspase-1 activation in the brains of R6/2 transgenic mouse models
mice and humans with the disease. In the mouse model, expression
of a dominant-negative caspase-1 mutant extended survival and
: [email protected]
delayed the appearance of neuronal inclusions, neurotransmitterreceptor alterations and onset of symptoms, indicating thatcaspase-1 is important in the pathogenesis of HD. The authors also
demonstrated that intracerebroventricular administration of acaspase inhibitor delayed disease progression and mortality in the
Alarcon G S (1998) Minocycline for the treatment of rheumatoid
arthritis. Rheum Dis Clin North Am 24: 489–499
mouse model. (Ona et al.
Berger A (2000) Minocycline slows progress of Huntington’s disease
Subsequently, Chen et al.
(2000) decided to evaluated the
therapeutic efficacy of minocycline in mouse model of HD after
Bonelli R M, Heuberger C, Reisecker F (2003) Minocycline for
Huntington’s disease: an open label study. Neurology 60:883–884
Yrjanheikki et al.
showed that mice treated with minocycline both
Chen M, Ona V O, Li M, Ferrante R J, Fink K B, Zhu S, Bian J, Guo
before and after the induction of stroke seemed to sustain less brain
L, Farrell L A, Hersch S M, Hobbs W, Vonsattel J P, Cha J H,
damage (Berger, 2000). Minocycline delayed disease progression,
Friedlander R M (2000) Minocycline inhibits caspase-1 andcaspase-3 expression and delays mortality in a transgenic
inhibited caspase-1 and caspase-3 mRNA upregulation, and
mouse model of Huntington disease. Nature Med 6: 797–801
decreased inducible nitric oxide synthetase activity in the R6/2
Denovan-Wright E M, Devarajan S, Dursun S M, Robertson H A
model. Survival was extended by 14%. Effective pharmacotherapy
(2002) Maintained improvement with minocycline of a patientwith advanced Huntington’s disease. J Psychopharmacol 16:
in R6/2 mice required caspase-1 and caspase-3 inhibition. (Chen et
Langevitz P, Livneh A, Bank I, Pras M (2000) Benefits and risks of
Minocycline is a second-generation tetracycline commonly
minocycline in rheumatoid arthritis. Drug Saf 22: 405–414
used for a prolonged period to treat acne and rheumatoid arthritis.
Ona V O, Li M, Vonsattel J P, Andrews L J, Khan S Q, Chung W M,
Frey A S, Menon A S, Li X J, Stieg P E, Yuan J, Penney J B,
(Alarcon, 1998; Patel et al.
, 1998; Langevitz et al.
, 2000) It
Young A B, Cha J H, Friedlander R M (1999) Inhibition of
effectively crosses the blood-brain barrier and inhibits IL-1β
caspase-1 slows disease progression in a mouse model ofHuntington’s disease. Nature 399: 263–267
converting enzyme and inducible nitric oxide synthase up-
Patel K, Cheshire D, Vance A (1998) Oral and systemic effects of
regulation in animal models of ischemic stroke. After ischemia,
prolonged minocycline therapy. Br Dent J 185: 560–562
minocycline inhibits caspase-1 and inducible nitric oxide
Tikka T M, Koistinaho J E (2001) Minocycline provides
synthetase upregulation, and reduces infarction (Chen et al.
neuroprotection against n-methyl-d-aspartate neurotoxicity byinhibiting microglia. J Immunol 166: 7527–7533
Minocycline protects neurons in mixed spinal cord cultures against
Yamamoto A, Lucas J J, Hen R (2000) Reversal of neuropathology
NMDA excitotoxicity (Tikka and Koistinaho, 2001).
and motor dysfunction in a conditional model of Huntington’s
What is the explanation for the findings of Denovan-Wright and
Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH,
our group? The disappearance of aggregates and symptoms in the
Koistinaho J (1999) A tetracycline derivative, minocycline,
HD mice studied by Yamamoto et al.
(2000) (i.e. by switching on
reduces inflammation and protects against focal cerebral
or off the mutant exon 1 HD gene) suggests that mutant proteins
ischemia with a wide therapeutic window. Proc NatlAcad Sci U S A 96:13496-13500
can be cleared even after the cells manifest dysfunction. Is the
NHS Greater Glasgow and Clyde Equality Impact Assessment Tool For Frontline Patient Services It is essential to follow the EQIA Guidance in completing this form Name of Current Service/Service Development/Service Redesign: Meticillen Resistant Staphylococcus Aureus (MRSA) Screening Project Please tick box to indicate if this is a :Current Service ; Service Development
Title: Impact of a new electronic handover system in surgeryAuthors: S. Ryan, J.M. O'riordan, S. Tierney, K.C. Conlon, P.F. RidgwayReceived Date: 9 June 2010Revised Date: 29 October 2010Accepted Date: 23 November 2010Please cite this article as: Ryan S, O'riordan JM, Tierney S, Conlon KC, Ridgway PF. Impact of anew electronic handover system in surgery, International Journal of Surgery (2010