Article
Clinical Neurology
Michael Dietrich, Hans-Peter Hartung, Philipp Albrecht
Summary: 4-aminopyridine is used as a symptomatic therapy in various neurological disorders, with potential neuroprotective features beyond its symptomatic action, particularly in patients with multiple sclerosis.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2021)
Article
Clinical Neurology
Cecilie Dollerup Skov, Christina Borgen Sorensen, Maria Thorning, Kate Lykke Lambertsen, Lars Henrik Frich, Henrik Boye Jensen, Anders Holsgaard-Larsen, Helle H. Nielsen
Summary: The purpose of this study was to evaluate changes in functional hand and walking measurements in multiple sclerosis patients with walking disability after fampridine treatment. The combination of self-reported walking capacity and walking endurance was found to be the most effective measurement for detecting clinically meaningful improvement after fampridine treatment.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Clinical Neurology
Maria A. Rocca, Paola Valsasina, Bruno Colombo, Vittorio Martinelli, Massimo Filippi
Summary: Fatigue in multiple sclerosis patients improved regardless of treatment. Changes in resting state functional connectivity were located in sensorimotor, inferior frontal, and subcortical regions for fampridine- and amantadine-treated patients, while in associative sensory cortices for placebo-treated patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Clinical Neurology
Sahar Ghorbanpour, Sarvenaz Rahimibarghani, Setareh Rohani, Mohsen Rastkar, Mahsa Ghajarzadeh
Summary: This systematic review and meta-analysis found that fampridine improves gait imbalance in patients with multiple sclerosis (MS).
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Sepehr Mamoei, Henrik Boye Jensen, Andreas Kristian Pedersen, Mikkel Karl Emil Nygaard, Simon Fristed Eskildsen, Ulrik Dalgas, Egon Stenager
Summary: In a 1-year longitudinal study, responders and non-responders to Fampridine treatment among persons with multiple sclerosis were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and MRI outcomes. Non-responders were found to have prolonged peripheral motor conduction times compared to responders. The study also showed associations between certain tests and measurements, such as the six spot step test with central motor conduction times and the symbol digit modalities test with T2-weighted lesion characteristics.
FRONTIERS IN NEUROLOGY
(2021)
Article
Cell Biology
Ulrike B. S. Hedrich, Stephan Lauxmann, Markus Wolff, Matthis Synofzik, Thomas Bast, Adrian Binelli, Jose M. Serratosa, Pedro Martinez-Ulloa, Nicholas M. Allen, Mary D. King, Kathleen M. Gorman, Bruria Ben Zeev, Michal Tzadok, Lily Wong-Kisiel, Dragan Marjanovic, Guido Rubboli, Sanjay M. Sisodiya, Florian Lutz, Harshad Pannikkaveettil Ashraf, Kirsten Torge, Pu Yan, Christian Bosselmann, Niklas Schwarz, Monika Fudali, Holger Lerche
Summary: Developmental and epileptic encephalopathies are severe disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms with limited treatment options. Through a precision medicine approach, it was found that the K+ channel blocker 4-aminopyridine could effectively alleviate symptoms in patients with KCNA2-encephalopathy caused by variants in the K(V)1.2 subunit. Results from n-of-1 trials showed that most patients benefited from the treatment with 4-aminopyridine, with well-tolerated dosages up to 2.6 mg/kg per day.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Clinical Neurology
Ali Amini Harandi, Hossein Pakdaman, Faezeh Karamiani, Faezeh Mohammadi, Siavash Shirzadeh Barough, Fatemeh Siavoshi, Saba Ilkhani, Mohammadali Sahraian
Summary: Using fampridine plus IVMP in the acute phase of transverse myelitis in MS patients improved the disease's symptoms and increased the daily activity ability of patients.
NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ivanka Kostadinova, Boycho Landzhov, Lyubomir Marinov, Lyubomir Vezenkov, Nikolai Danchev
Summary: The study assessed the effects of newly synthesized 4-AP derivatives on a cuprizone-induced mouse model of brain demyelination, with compounds 4b and 4c showing promise in improving memory processes and reversing the effects of cuprizone.
Article
Engineering, Biomedical
Maxime Valet, Souraya El Sankari, Vincent Van Pesch, Christine Detrembleur, Thierry Lejeune, Gaetan Stoquart
Summary: This study found that prolonged release-fampridine can improve gait pattern in patients with multiple sclerosis by increasing knee flexion and reducing external mechanical work. However, no significant differences were observed in other walking tests and patient-reported outcomes at the group level.
CLINICAL BIOMECHANICS
(2021)
Article
Engineering, Biomedical
Maria Thorning, Helle Hvilsted Nielsen, Lars Henrik Frich, Henrik Boye Jensen, Kate Lykke Lambertsen, Anders Holsgaard-Larsen
Summary: The study aimed to investigate the effects of Fampridine treatment on gait quality and function in patients with multiple sclerosis. The findings showed that while Fampridine treatment improved gait function, there was no change in the overall kinematic quality of gait.
CLINICAL BIOMECHANICS
(2022)
Article
Clinical Neurology
Maria A. Rocca, Paola Valsasina, Maria Teresa Lamanna, Bruno Colombo, Vittorio Martinelli, Massimo Filippi
Summary: This study aimed to investigate the pathogenesis of fatigue in multiple sclerosis (MS) patients. The researchers found that there were modifications in fatigue severity and resting state functional connectivity (RS FC) in monoaminergic networks after different symptomatic treatments. These modifications involved dopamine, noradrenaline, and serotonin-related RS FC.
JOURNAL OF NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Yang Sun, Karla M. Ramos-Torres, Pedro Brugarolas
Summary: [18F]3-fluoro-4-aminopyridine ([18F]3F4AP) is a PET tracer used for imaging demyelination. It was found to be stable in anesthetized rodents and nonhuman primates, but its stability is greatly decreased in awake humans and mice. The metabolism of 3F4AP by the enzyme CYP2E1 was investigated, and its primary metabolites were identified as 5-hydroxy-3F4AP and 3F4AP N-oxide. Deuteration did not decrease the rate of CYP2E1-mediated oxidation, but the findings provide insights into the metabolic stability of drugs and PET ligands.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Review
Pharmacology & Pharmacy
Cinzia Dello Russo, Kathryn Anne Scott, Munir Pirmohamed
Summary: Dimethyl fumarate (DMF) is a first line medication for multiple sclerosis, but concerns have been raised regarding its adverse effects such as lymphopenia. The molecular mechanisms underlying these effects are not well understood, and the relative toxicity of DMF and its metabolite MMF in vivo remains unclear.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Neurosciences
Andrej Roczkowsky, Matthew A. L. Doan, Brittyne A. Hlavay, Manmeet K. Mamik, William G. Branton, Brienne A. McKenzie, Leina B. Saito, Laura Schmitt, Gary Eitzen, Francesca Di Cara, Melinda Wuest, Frank Wuest, Richard Rachubinski, Christopher Power
Summary: This study investigates the peroxisomal injury and the effects of peroxisome-restorative therapy on inflammatory demyelination in multiple sclerosis (MS) models. It reveals that peroxisomes play critical roles in CNS homeostasis and their dysfunction is associated with neuroinflammation and demyelination in MS. The therapeutic peroxisome proliferator, 4-phenylbutyrate (4-PBA), shows potential in mitigating neuroinflammation and promoting myelin repair in MS.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Crystallography
Laura Marincas, Graziella Liana Turdean, Monica Tosa, Zsolt Kovacs, Bela Kovacs, Reka Barabas, Noemi-Izabella Farkas, Liliana Bizo
Summary: The study demonstrated the suitability of Si-HAP for drug delivery of 4AP, with a release rate five times slower than HAP, attributed to the chemical bonding between silicon and the drug.