Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial

Orphanet Journal of Rare Diseases

Naoki Ishiguro⁴  Kinji Ohno⁵  Benedetta C Sallustio²  John D Horowitz²  Izumi Kadono¹  Masaki Matsushita⁴  Kenichi Mishima⁴  Hiroshi Kaneko⁴  Masataka Achiwa³  Hiroshi Kitoh⁴ 

[1] Department of Rehabilitation, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan;Department of Cardiology and Clinical Pharmacology, Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia;Department of Radiological Technology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan;Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan;Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan

关键词: Whole body CT;    Biomarker;    Clinical trial;    Perhexiline maleate;    Fibrodysplasia ossificans progressiva;   

Others  :  863469
DOI  :  10.1186/1750-1172-8-163

 received in 2013-04-24, accepted in 2013-10-13,  发布年份 2013

【 摘 要 】

Background

Currently, there are no effective medical treatment options to prevent the formation of heterotopic bones in fibrodysplasia ossificans progressiva (FOP). By the drug repositioning strategy, we confirmed that perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in model cells and mice. Here, we conducted a prospective study to assess the efficacy and safety of Pex in the treatment of FOP patients.

Methods

FOP patients in this open-label single-center study were treated with Pex for a total of 12 months, and followed up for 12 consecutive months after medication discontinuation. The safety of the treatment was assessed regularly by physical and blood examinations. The efficacy of Pex for preventing heterotopic ossifications was evaluated by the presence of flare-ups, measurements of serum bone markers, and changes in the total bone volume calculated by the three-dimensional computed tomography (3D-CT) images.

Results

Five patients with an average age of 23.4 years were enrolled. Within safe doses of Pex administration in each individual, there were no drug-induced adverse effects during the medication phase. Three patients showed no intense inflammatory reactions during the study period, while two patients had acute flare-ups around the hip joint without evidence of trauma during the medication phase. In addition, one of them became progressively incapable of opening her mouth over the discontinuation phase. Serum levels of alkaline phosphatase (ALP) and bone specific ALP (BAP) were significantly and synchronously increased with the occurrence of flare-ups. Volumetric 3D-CT analysis demonstrated a significant increase in the total bone volume of Case 2 (378 cm³) and Case 3 (833 cm³) during the two-year study period.

Conclusions

We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP.

【 授权许可】

   
2013 Kitoh et al.; licensee BioMed Central Ltd.

【 图 表 】

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