Search Our Scientific Publications & Authors

J Mov Disord 2021 May 26;14(2):148-152. Epub 2021 May 26.

Department of Radiology, CEDIMAT, Santo Domingo, Dominican Republic.

Objective: To determine the volume changes in gray and white matter during a long-term follow-up in patients suffering from pantothenate kinase-associated neurodegeneration (PKAN).

Methods: Magnetic resonance imaging was repeated in 13 patients and 14 age-matched controls after a mean interval of more than 7 years. T1-weighted sequences were evaluated by fully automated atlas-based volumetry, compared between groups and correlated with disease progression. Read More

Case Rep Radiol 2021 7;2021:6633217. Epub 2021 May 7.

Children's Hospital, Radiology Department, Mohamed V University, Rabat, Morocco.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation caused by a recessive mutation in pantothenate kinase 2 gene (PANK2). We present a case of an 11 year-old boy presenting extrapyramidal signs and developmental regression. T2-weighted images showed the classic eye of the tiger sign seen in pantothenate kinase-associated neurodegeneration. Read More

PLoS One 2021 21;16(5):e0251981. Epub 2021 May 21.

ADME/DMPK Department, IRBM SpA, Pomezia, Roma, Italy.

Coenzyme A (CoA) is a fundamental cofactor involved in a number of important biochemical reactions in the cell. Altered CoA metabolism results in severe conditions such as pantothenate kinase-associated neurodegeneration (PKAN) in which a reduction of the activity of pantothenate kinase isoform 2 (PANK2) present in CoA biosynthesis in the brain consequently lowers the level of CoA in this organ. In order to develop a new drug aimed at restoring the sufficient amount of CoA in the brain of PKAN patients, we looked at its turnover. Read More

Mov Disord 2021 May 18. Epub 2021 May 18.

Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.

Background: This review highlights the recent scientific advances that have enabled rational design of novel clinical trials for pantothenate kinase-associated neurodegeneration (PKAN), a rare autosomal recessive neurogenetic disorder associated with progressive neurodegenerative changes and functional impairment. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in pantothenate kinase 2 (PANK2) enzyme activity, with consequent disruption of coenzyme A (CoA) synthesis, and subsequent accumulation of brain iron. The clinical phenotype is varied and may include dystonia, rigidity, bradykinesia, postural instability, spasticity, loss of ambulation and ability to communicate, feeding difficulties, psychiatric issues, and cognitive and visual impairment. Read More

Orphanet J Rare Dis 2021 May 5;16(1):201. Epub 2021 May 5.

Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas, Universidad Pablo de Olavide, Carretera de Utrera Km 1, 41013, Sevilla, Spain.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Read More

Front Neurol 2021 15;12:629414. Epub 2021 Apr 15.

Department of Neurology With Friedrich Baur Institute, University Hospital of Ludwig-Maximilians-Universität München, Munich, Germany.

Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra. As of today, 15 distinct monogenetic disease entities have been identified. The four most common forms are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN) and mitochondrial membrane protein-associated neurodegeneration (MPAN). Read More

Psychiatr Genet 2021 Jun;31(3):95-99

Department of Medical Genetics, Centro Médico Ecatepec, Instituto de Seguridad Social del Estado de México y Municipios, Ecatepec City, México.

The proband in this study was a 16-year-old Mexican girl with psychotic and dyskinetic symptoms, and brain MRI showed at the basal ganglia the 'eye-of-the-tiger' sign. DNA direct sequencing identified a novel compound heterozygous mutation in the PANK2 gene. The diagnosis of pantothenate kinase-associated neurodegeneration (PKAN) disorder was made. Read More

Front Neurosci 2021 18;15:618435. Epub 2021 Feb 18.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. Read More

Brain Commun 2020 26;2(2):fcaa178. Epub 2020 Oct 26.

Kids Neuroscience Centre, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalization of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. Read More

eNeurologicalSci 2021 Mar 19;22:100314. Epub 2021 Jan 19.

Brain Imaging Facility, IZKF Aachen, RWTH Aachen University, Aachen, Germany.

Purpose: To demonstrate deviations of functional connectivity within the motor system in dystonic patients suffering from Pantothenate Kinase Associated Neurodegeneration, a genetic and metabolic disease, which is characterized by a primary lesion in the globus pallidus.

Material And Methods: Functional Magnetic Resonance Imaging data were measured during resting state in 12 patients suffering from a confirmed mutation of the PANK2 gene. In this region-of-interest based analysis, data were evaluated in respect to correlation of signal time course between basal ganglia, motor-related cortical regions and cerebellum, were related to clinical data and were compared to a control group of 20 healthy volunteers. Read More

Stem Cell Res 2021 03 22;51:102190. Epub 2021 Jan 22.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Neurodegeneration with brain iron accumulation (NBIA) is a genetically and phenotypically heterogeneous group of inherited neurodegenerative disorder characterized by basal ganglia iron deposition. Mutations in Pantothenate Kinase 2 (PANK2) are major genetic causes for patients with NBIA. The location of PANK2 in the mitochondria suggests mutant PANK2 causing mitochondrial dysfunction in the pathogenesis of NBIA. Read More

Int J Mol Sci 2020 Dec 30;22(1). Epub 2020 Dec 30.

Department of Chemistry, Life Science and Environmental Sustainability, University of Parma, 43124 Parma, Italy.

Mutations in the pantothenate kinase 2 gene () are the cause of pantothenate kinase-associated neurodegeneration (PKAN), the most common form of neurodegeneration with brain iron accumulation. Although different disease models have been created to investigate the pathogenic mechanism of PKAN, the cascade of molecular events resulting from CoA synthesis impairment is not completely understood. Moreover, for PKAN disease, only symptomatic treatments are available. Read More

Int J Mol Sci 2020 Dec 19;21(24). Epub 2020 Dec 19.

Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy.

COASY protein-associated neurodegeneration (CoPAN) is a rare but devastating genetic autosomal recessive disorder of inborn error of CoA metabolism, which shares with pantothenate kinase-associated neurodegeneration (PKAN) similar features, such as dystonia, parkinsonian traits, cognitive impairment, axonal neuropathy, and brain iron accumulation. These two disorders are part of the big group of neurodegenerations with brain iron accumulation (NBIA) for which no effective treatment is available at the moment. To date, the lack of a mammalian model, fully recapitulating the human disorder, has prevented the elucidation of pathogenesis and the development of therapeutic approaches. Read More

J Med Chem 2020 12 15;63(24):15785-15801. Epub 2020 Dec 15.

Travere, 3721 Valley Centre Drive, San Diego, California 92130, United States.

Mutations in the human PANK2 gene are implicated in neurodegenerative diseases such as pantothenate kinase-associated neurodegeneration (PKAN) and result in low levels of coenzyme-A (CoA) in the CNS due to impaired production of phosphopantothenic acid (PPA) from vitamin B5. Restoration of central PPA levels by delivery of exogenous PPA is a recent strategy to reactivate CoA biosynthesis in PKAN patients. Fosmetpantotenate is an oral PPA prodrug. Read More

Bull Exp Biol Med 2020 Nov 25;170(1):58-63. Epub 2020 Nov 25.

Section of Biotechnology, Brescia, Italy.

Mutations in pank2 gene encoding pantothenate kinase 2 determine a pantothenate kinase-associated neurodegeneration, a rare disorder characterized by iron deposition in the globus pallidus. To extend our previous work, we performed microinjections of a new pank2-specific morpholino to zebrafish embryos and thoroughly analyzed vasculature development. Vessels development was severely perturbed in the head, trunk, and tail, where blood accumulation was remarkable and associated with dilation of the posterior cardinal vein. Read More

Mov Disord 2021 06 16;36(6):1342-1352. Epub 2020 Nov 16.

Research and Development, Retrophin, Inc., San Diego, California, USA.

Background: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments.

Objectives: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression.

Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Read More

Int J Neurosci 2020 Oct 14:1-7. Epub 2020 Oct 14.

Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

Aim: Pantothenate kinase associated neurodegeneration (PKAN) is a severe autosomal recessive rare disease and characterized by iron accumulation in the basal ganglia. To investigate the pathogenesis of this disease in two sibling patients with PANK in a Chinese family, whole-exome variant detection and functional analysis were performed.

Materials And Methods: Clinical and radiographic investigations were performed in the two brother patients. Read More

Mov Disord Clin Pract 2020 Sep 29;7(Suppl 3):S71-S73. Epub 2020 Sep 29.

Department of Neurology University of Colorado School of Medicine Aurora Colorado USA.

J Mov Disord 2021 Jan 21;14(1):86-88. Epub 2020 Sep 21.

Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA.

Orphanet J Rare Dis 2020 09 14;15(1):248. Epub 2020 Sep 14.

Department of Pediatrics, Peking University First Hospital, No.1, Xi'an Men Street, West District, Beijing, 100034, China.

Objective: This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).

Methods: A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. Read More

Neuroradiol J 2020 Dec 27;33(6):479-485. Epub 2020 Aug 27.

Department of Neurology, Centros de Diagnóstico y Medicina Avanzada y de Conferencias Médicas y Telemedicina, Dominican Republic.

Background And Purpose: The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron.

Material And Methods: Under resting conditions, cerebral blood flow was measured by the magnetic resonance imaging technique of arterial spin labelling in cortical areas and basal ganglia in eight pantothenate kinase-associated neurodegeneration patients and 14 healthy age-matched control subjects and correlated to T2* time of these areas and - in patients - to clinical parameters.

Results: Despite highly significant differences of T2* time of the globus pallidus (20 vs 39 ms,  < 0. Read More

Int J Mol Sci 2020 May 22;21(10). Epub 2020 May 22.

IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Pantothenate Kinase-associated Neurodegeneration (PKAN) belongs to a wide spectrum of diseases characterized by brain iron accumulation and extrapyramidal motor signs. PKAN is caused by mutations in PANK2, encoding the mitochondrial pantothenate kinase 2, which is the first enzyme of the biosynthesis of Coenzyme A. We established and characterized glutamatergic neurons starting from previously developed PKAN Induced Pluripotent Stem Cells (iPSCs). Read More

Neurocase 2020 06 20;26(3):175-182. Epub 2020 Apr 20.

The First Affiliated Hospital of Zhengzhou University, Zhengzhou University , Zhengzhou, Henan, China.

Panthothenate kinase-associated neurodegeneration (PKAN) is arare neurodegeneration caused by mutations in the pantothenate kinase () gene, which is located on chromosome 20p13. These mutations result in iron accumulation in the brain basal ganglia leading to parkinsonism, dysarthria, spasticity, cognitive impairment, and retinopathy. Herein, we report acase of adult-onset PKAN who presented with young-onset action tremor, bradykinesia, dysarthria, and bilateral interossei atrophy. Read More

Eur J Case Rep Intern Med 2020 13;7(3):001488. Epub 2020 Feb 13.

Service de Médecine Interne, Diabète et Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

We report the case of a 27-year-old man presenting with slowly progressive extrapyramidal dysfunction and learning disability considered to have a syndromic intellectual disability. The re-evaluation of the clinical features and the investigations performed led to the diagnosis of atypical pantothenate kinase-associated neurodegeneration (PKAN).

Learning Points: Patients with an intellectual disability should be carefully evaluated. Read More

CNS Neurosci Ther 2020 07 11;26(7):754-761. Epub 2020 Feb 11.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Aims: To investigate the natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration.

Methods: We collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. Read More

J Assoc Physicians India 2020 Jan;68(1):62

Gandhi Medical College.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020011. Epub 2020 Jan 1.

Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus.

Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G. J. following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use. Read More

Biochim Biophys Acta Mol Basis Dis 2020 05 7;1866(5):165663. Epub 2020 Jan 7.

St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA. Electronic address:

Pantothenate kinase (PanK) is the first enzyme in the coenzyme A (CoA) biosynthetic pathway. The differential expression of the four-active mammalian PanK isoforms regulates CoA levels in different tissues and PANK2 mutations lead to Pantothenate Kinase Associated Neurodegeneration (PKAN). The molecular mechanisms that potentially underlie PKAN pathophysiology are investigated in a mouse model of CoA deficiency in the central nervous system (CNS). Read More

J Neurol Sci 2020 03 19;410:116639. Epub 2019 Dec 19.

Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK; Center for Neurology and Hertie Institute for Clinical Brain Research, Eberhard Karls-University, Tübingen, Germany. Electronic address: