Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study

Xuting Chang,Bufan Yao,Ye Wu,Jingmin Wang,Jie Zhang,Yuwu Jiang

doi:10.1186/s13023-020-01530-5

Abstract

ObjectiveThis study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).MethodsA single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson’s Disease Rating Scale (UPDRS) I–III and Fahn–Marsden (FM) score from baseline to week 24 after treatment.ResultsFifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60 mg/kg per day, there was no difference in either UPDRS I–III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as “slightly improved” by doctors through blinded video assessment. Patients with lower baseline UPDRS I–III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study.ConclusionsPantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day.Trial registrationClinical trial registration number at www.chictr.org.cn:ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered.

Highlights

Pantothenate kinase-associated neurodegeneration (PKAN, OMIM#234200, formerly known as Hallervorden–Spatz syndrome), an autosomal recessive disease caused by mutations in the PANK2 [1], is classified into two subtypes, namely, classic and atypical phenotype [2]
The mutations in PANK2 result in decreased activity of pantothenic acid kinase 2, which is essential for the biosynthesis of coenzyme A (CoA) using pantothenic acid, thereby leading to the reduction of CoA and iron accumulation in specific brain regions [4]
As well as blood routine remained normal during the study period. In this pilot study on 15 children with pantothenate kinaseassociated neurodegeneration (PKAN), we did not find 24 weeks of pantethine could significantly improve the motor function, but we found that it may delay the progression of motor dysfunction

Summary

Introduction

Pantothenate kinase-associated neurodegeneration (PKAN, OMIM#234200, formerly known as Hallervorden–Spatz syndrome), an autosomal recessive disease caused by mutations in the PANK2 [1], is classified into two subtypes, namely, classic and atypical phenotype [2]. Two-thirds of patients are classic phenotype, which is usually characterized by dystonia before 10 years of age and loss of ambulation 10–15 years after the disease onse t[3]. The mutations in PANK2 result in decreased activity of pantothenic acid kinase 2, which is essential for the biosynthesis of coenzyme A (CoA) using pantothenic acid, thereby leading to the reduction of CoA and iron accumulation in specific brain regions [4]. Therapies tried in patients with PKAN included deep brain stimulation (DBS), deferiprone and fosmetpantotenate (RE-024).

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