Effect of pioglitazone treatment in a patient with secondary multiple sclerosis

Journal of Neuroinflammation

Douglas L Feinstein³  Daniel J Broeske⁴  Navin M Amin²  Rashmi Saini²  Michael T Heneka¹  Harrihar A Pershadsingh¹ 

[1] Department of Neurology, University of Bonn, Bonn, Germany;Departments of Family Medicine, Kern Medical Center, Bakersfield, and University of California, Irvine, California, USA;Department of Anesthesiology, University of Illinois, Chicago, Illinois, USA;Department of Internal Medicine, Kern Medical Center, Bakersfield, California, USA

关键词: inflammation;    pioglitazone;    PPARγ;    thiazolidinedione;    Multiple sclerosis;   

Others  :  1213704
DOI  :  10.1186/1742-2094-1-3

 received in 2004-03-24, accepted in 2004-04-20,  发布年份 2004

【 摘 要 】

Background

Ligands of the peroxisome proliferator-activated receptor-gamma (PPARγ) induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARγ agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS.

Case presentation

The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32%) and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events.

Conclusions

In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events. Pioglitazone should therefore be considered for further testing of therapeutic potential in MS patients.

【 授权许可】

   
2004 Pershadsingh et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

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