GMDP for psoriasis

Authors: D. Williamson, M. Chawla, R. Marks
Edition: THE LANCET, August 1998, Volume 352, Issue 9127, Page 545
Year: 1998

Annotation: GMDP, N-acetylglucosaminyl-N-acetylmuramyldipeptide, is a derivative of muramyl dipeptide, MDP, the peptidoglycan fraction of mycobacterial cell walls which acts as the functional component in Freund's complete adjuvant. Both MDP and GMDP have aroused interest as immunomodulants; GMDP is considered to be less pyrogenic and to be less toxic than MDP. In-vitro studies of GMDP have shown selective immunostimulant and anti-inflammatory properties, as well as both up-regulation and down-regulation of components of the cutaneous immune system. It has been suggested that GMDP may be effective in the treatment of psoriasis. Pilot studies in Moscow have supported this suggestion.

Keywords: gmdp, n-acetylglucosaminyl-n-acetylmuramyldipeptide, mdp, psoriasis

RESEARCH LETTERS

THE LANCET, August 1998, Volume 352, Issue 9127, Page 545

GMDP for psoriasis

D Williamson, M Chawla, R Marks

GMDP, N-acetylglucosaminyl-N-acetylmuramyldipeptide, is a derivative of muramyl dipeptide, MDP, the peptidoglycan fraction of mycobacterial cell walls which acts as the functional component in Freund’s complete adjuvant. Both MDP and GMDP have aroused interest as immunomodulants; GMDP is considered to be less pyrogenic  and to be less toxic than MDP. In-vitro studies of GMDP have shown selective immunostimulant and anti-inflammatory properties, as well as both up-regulation and down-regulation of components of the cutaneous immune system. It has been suggested that GMDP may be effective in the treatment of psoriasis. Pilot studies in Moscow have supported this suggestion.

The study we report was approved by the Bro T af Local Research Ethics Committee. Ten patients with stable, chronic plaque psoriasis were treated with GMDP. Patients were given 20 mg of oral GMDP daily for 14 days. Severity of psoriasis was assessed at baseline, 3, 7, and 14 days by the psoriasis area and severity index (PASI) score, and plaque thickness was determined by pulsed A-scan ultrasound. Assessments of overall improvement by patients and investigators, and assessment of itch with a visual analogue score (VAS) were also made. Blood samples were taken before and after treatment to assess any change in activity of T -lymphocyte subsets.

Results showed significant change in PASI score with time (table). There was a reduction in plaque thickness, but this was not significant (p=0·0613, paired t test) nor was a reduction in VAS (p=0·70). Assessments of response to treatment by investigators at the end of the study was that there showed an improvement in all ten cases, but assessments by patients was of improvement in eight and no change in two. Four patients failed to complete the 14-day course of GMDP; two patients had epigastric pain and vomiting during the second week of treatment, one was withdrawn due to coryzal symptoms, a respiratory infection with fever (GMDP is pyrogenic3), and the other withdrew because of muscle and joint pains. Lymphocyte subset analysis showed no abnormalities and no change.

After treatment with GMDP, there was a marked improvement in the psoriasis of all patients; although possible side-effects limited the use of the drug in four of ten patients. Further studies, with the option of reducing the dosage if side-effects occurred would be useful to assess the efficacy of an extended treatment period.

Ellouz F, Adams A, Ciorbaru, Lederer D. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res 1974; 59: 1317–25.

Andronova T , Ivonova V. T he structure and immunomodulating function of glucosaminylmuramyl peptides. Sov Med Rev D Immunol 1991; 4: 1–63.

Dinarella CA, Elin RJ, Chedid L, Wolff SM. The pyrogenicity of the synthetic adjuvant muramyl dipeptide and two structural analogues. J Infect Dis 1978; 138: 760–67.

Chedid L, Parant M, Parant F, Lefrancier P, Choay J, Lederer E. Enhancement of non specific immunity to Klebsiella pneumoniae infection by a synthetic adjuvant (N-acetylmuramyl-L-alanyl-D- isoglutamine) and several analogues. Proc Natl Acad Sci 1977; 74: 2089.

Zidek Z, Capkova J, Boubelik M, Masek K. Opposite effects of the synthetic immunomodulator muramyl dipeptide on the rejection of mouse skin allografts. Eur J Immunol 1983; 13: 859.

Department of Dermatology, University Hospital of Wales and University of Wales College of Medicine, Cardiff CF4 4XN, UK (D Williamson)

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