Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN
Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speec...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Case Reports in Neurological Medicine |
| Online Access: | http://dx.doi.org/10.1155/2017/3247034 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556755927695360 |
|---|---|
| author | Yiolanda-Panayiota Christou George A. Tanteles Elena Kkolou Annita Ormiston Kostas Konstantopoulos Maria Beconi Randall D. Marshall Horacio Plotkin Kleopas A. Kleopa |
| author_facet | Yiolanda-Panayiota Christou George A. Tanteles Elena Kkolou Annita Ormiston Kostas Konstantopoulos Maria Beconi Randall D. Marshall Horacio Plotkin Kleopas A. Kleopa |
| author_sort | Yiolanda-Panayiota Christou |
| collection | DOAJ |
| description | Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief. We describe the treatment of the first, later-onset PKAN patient with oral fosmetpantotenate (previously known as RE-024), a novel replacement therapy developed to bypass the enzymatic defect. Methods. This was an open-label, uncontrolled, 12-month treatment with fosmetpantotenate of a single patient with a later-onset, moderately severe, and slowly progressive form of PKAN. Results. The patient showed improvement in all clinical parameters including the Unified Parkinson’s Disease Rating Scale (UPDRS), Barry-Albright Dystonia Scale, the EuroQol five-dimensional three-level (EQ-5D-3L) scale, timed 25-foot walk test, and electroglottographic speech analysis. Fosmetpantotenate was well-tolerated with only transient liver enzyme elevation which normalized after dose reduction and did not recur after subsequent dose increases. Conclusions. Fosmetpantotenate showed promising results in a single PKAN patient and should be further studied in controlled trials. |
| format | Article |
| id | doaj-art-8cdb795e117241519cd8e48effa0d8c8 |
| institution | Kabale University |
| issn | 2090-6668 2090-6676 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Neurological Medicine |
| spelling | doaj-art-8cdb795e117241519cd8e48effa0d8c82025-02-03T05:44:23ZengWileyCase Reports in Neurological Medicine2090-66682090-66762017-01-01201710.1155/2017/32470343247034Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKANYiolanda-Panayiota Christou0George A. Tanteles1Elena Kkolou2Annita Ormiston3Kostas Konstantopoulos4Maria Beconi5Randall D. Marshall6Horacio Plotkin7Kleopas A. Kleopa8Neurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusClinical Genetics Clinic, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusNeurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusNeurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusEuropean University Cyprus, Nicosia, CyprusRetrophin Inc., New York, NY, USARetrophin Inc., New York, NY, USARetrophin Inc., New York, NY, USANeurology Clinics, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusObjective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief. We describe the treatment of the first, later-onset PKAN patient with oral fosmetpantotenate (previously known as RE-024), a novel replacement therapy developed to bypass the enzymatic defect. Methods. This was an open-label, uncontrolled, 12-month treatment with fosmetpantotenate of a single patient with a later-onset, moderately severe, and slowly progressive form of PKAN. Results. The patient showed improvement in all clinical parameters including the Unified Parkinson’s Disease Rating Scale (UPDRS), Barry-Albright Dystonia Scale, the EuroQol five-dimensional three-level (EQ-5D-3L) scale, timed 25-foot walk test, and electroglottographic speech analysis. Fosmetpantotenate was well-tolerated with only transient liver enzyme elevation which normalized after dose reduction and did not recur after subsequent dose increases. Conclusions. Fosmetpantotenate showed promising results in a single PKAN patient and should be further studied in controlled trials.http://dx.doi.org/10.1155/2017/3247034 |
| spellingShingle | Yiolanda-Panayiota Christou George A. Tanteles Elena Kkolou Annita Ormiston Kostas Konstantopoulos Maria Beconi Randall D. Marshall Horacio Plotkin Kleopas A. Kleopa Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN Case Reports in Neurological Medicine |
| title | Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN |
| title_full | Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN |
| title_fullStr | Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN |
| title_full_unstemmed | Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN |
| title_short | Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN |
| title_sort | open label fosmetpantotenate a phosphopantothenate replacement therapy in a single patient with atypical pkan |
| url | http://dx.doi.org/10.1155/2017/3247034 |
| work_keys_str_mv | AT yiolandapanayiotachristou openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT georgeatanteles openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT elenakkolou openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT annitaormiston openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT kostaskonstantopoulos openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT mariabeconi openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT randalldmarshall openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT horacioplotkin openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan AT kleopasakleopa openlabelfosmetpantotenateaphosphopantothenatereplacementtherapyinasinglepatientwithatypicalpkan |