Lafora Disease

A form of stimulus sensitive MYOCLONIC EPILEPSY inherited as an autosomal recessive condition. The most common presenting feature is a single seizure in the second decade of life. This is followed by progressive myoclonus, myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, and severe motor and coordination impairments. Most affected individuals do not live past the age of 25 years. Concentric amyloid (Lafora) bodies are found in neurons, liver, skin, bone, and muscle (From Menkes, Textbook of Childhood Neurology, 5th ed, pp111-110).

Also Known As:

Epilepsy Progressive Myoclonic 2; Epilepsy, Progressive Myoclonic 2A; Lafora Body Disease; Lafora Body Disease, Late Onset; Lafora Body Disorder; Lafora Progressive Myoclonic Epilepsy; Lafora Progressive Myoclonus Epilepsy; Lafora Type Progressive Myoclonic Epilepsy; Lafora-Body Disease, Late Onset; Late Onset Lafora Body Disease; Myoclonic Epilepsy of Lafora; Progressive Myoclonic Epilepsy Type 2; Progressive Myoclonic Epilepsy, Lafora; Progressive Myoclonus Epilepsy, Lafora Type; Lafora Myoclonic Epilepsy; Epilepsy, Progressive Myoclonic, Lafora; Progressive Myoclonic Epilepsy, Lafora Type

Networked: 235 relevant articles (8 outcomes, 13 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neuroinflammatory Diseases
2.	Progressive Myoclonic Epilepsies (Progressive Myoclonic Epilepsy)
3.	Unverricht-Lundborg Syndrome (Disease, Unverricht)
4.	Myoclonus (Nocturnal Myoclonus)
5.	Glycogen Storage Disease (Glycogenosis)

Experts

1.	Minassian, Berge A: 33 articles (01/2022 - 01/2002)
2.	Sanz, Pascual: 32 articles (06/2021 - 12/2003)
3.	Gentry, Matthew S: 22 articles (07/2021 - 06/2005)
4.	Ganesh, Subramaniam: 22 articles (03/2021 - 05/2002)
5.	Roach, Peter J: 21 articles (01/2020 - 12/2004)
6.	Wang, Peixiang: 19 articles (01/2022 - 12/2010)
7.	Zhao, Xiaochu: 15 articles (01/2022 - 10/2003)
8.	Guinovart, Joan J: 11 articles (02/2022 - 11/2007)
9.	DePaoli-Roach, Anna A: 11 articles (01/2020 - 01/2007)
10.	Romá-Mateo, Carlos: 11 articles (01/2016 - 01/2011)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Lafora Disease:

1.	perampanelIBA 01/01/2013 - "Sustained seizure remission on perampanel in progressive myoclonic epilepsy (Lafora disease)." 01/01/2021 - "Frontal Hypoperfusion and the Effectiveness of Perampanel in Long-Lived Patient with Lafora Disease." 01/01/2016 - "Efficacy and tolerability of perampanel in ten patients with Lafora disease." 01/01/2014 - "Perampanel is the first potentially efficacious treatment for Lafora disease. " 01/01/2014 - "Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel."
2.	Glucose (Dextrose)FDA LinkGeneric 04/01/2010 - "Posterior glucose hypometabolism in Lafora disease: early and late FDG-PET assessment." 12/01/1999 - "Glucose metabolism evaluated by positron emission tomography in Lafora disease." 02/01/1995 - "Based on these findings and review of the literature, it is unlikely that there is a significant deficit in cortical energy metabolism in patients with Lafora disease and it would be less plausible to have some enzymatic deficits in glucose metabolic process." 10/20/2020 - "Neuroimaging studies of patients with Lafora disease have shown different degrees of brain atrophy, decreased glucose brain uptake and alterations on different brain metabolites mainly in the frontal cortex, basal ganglia and cerebellum. " 01/01/2020 - "To describe cerebral glucose metabolism pattern as assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in Lafora disease (LD), a rare, lethal form of progressive myoclonus epilepsy caused by biallelic mutations in EPM2A or NHLRC1. "
3.	polyglucosanIBA 03/23/2023 - "Deciphering the Polyglucosan Accumulation Present in Lafora Disease Using an Astrocytic Cellular Model." 12/01/2022 - "Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. " 09/01/2021 - "Lafora disease is a genetic neurodegenerative metabolic disorder caused by insoluble polyglucosan aggregate accumulation throughout the central nervous system and body. " 07/15/2020 - "Polyglucosan body structure in Lafora disease." 10/01/2018 - "Astrocytes and neurons produce distinct types of polyglucosan bodies in Lafora disease."
4.	Proteins (Proteins, Gene)FDA Link 09/01/2018 - "Correction to: Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease." 01/01/2018 - "Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With EPM2B Repeat Expansion." 12/01/2015 - "Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease." 08/14/2015 - "Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway." 03/01/2014 - "PTG protein depletion rescues malin-deficient Lafora disease in mouse."
5.	Ubiquitin-Protein Ligases (Ubiquitin-Protein Ligase)IBA 01/01/2023 - "P-Rex1 is a novel substrate of the E3 ubiquitin ligase Malin associated with Lafora disease." 06/14/2005 - "Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin." 10/01/2019 - "In this work, we present new in vivo evidence of a GLT-1 dysfunction, contributing to increased levels of extracellular glutamate in the hippocampus of a mouse model of Lafora disease (Epm2b-/-, lacking the E3-ubiquitin ligase malin). " 01/28/2014 - "Lafora disease can be caused by defects in the EPM2A gene, which encodes the laforin protein phosphatase, or in the NHLRC1 gene (also called EPM2B) codifying the malin E3 ubiquitin ligase. " 07/01/2012 - "Mutations in either EPM2A, the gene encoding a dual-specificity phosphatase named laforin, or NHLRC1, the gene encoding an E3 ubiquitin ligase named malin, cause Lafora disease in humans. "
6.	UbiquitinIBA 02/24/2012 - "Using yeast-two hybrid screening followed by co-immunoprecipitation assay, we have found that the Lafora disease ubiquitin ligase malin interacts with dishevelled2, a key mediator of Wnt signaling pathway. " 08/01/2010 - "The laforin-malin complex, involved in Lafora disease, promotes the incorporation of K63-linked ubiquitin chains into AMP-activated protein kinase beta subunits." 01/08/2010 - "Co-chaperone CHIP stabilizes aggregate-prone malin, a ubiquitin ligase mutated in Lafora disease." 10/01/2011 - "Lafora disease ubiquitin ligase malin promotes proteasomal degradation of neuronatin and regulates glycogen synthesis." 03/29/2013 - "Lafora disease (LD) is a teenage-onset inherited progressive myoclonus epilepsy characterized by the accumulations of intracellular inclusions called Lafora bodies and caused by mutations in protein phosphatase laforin or ubiquitin ligase malin. "
7.	TrehaloseIBA 06/20/2022 - "Trehalose Treatment in Zebrafish Model of Lafora Disease." 03/01/2021 - "Trehalose Ameliorates Seizure Susceptibility in Lafora Disease Mouse Models by Suppressing Neuroinflammation and Endoplasmic Reticulum Stress."
8.	Zonisamide (Zonegran)FDA LinkGeneric 09/01/2001 - "Long-term observations of two siblings with Lafora disease treated with zonisamide." 09/01/2016 - "Newer drugs which have been shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. "
9.	Levetiracetam (Keppra)FDA LinkGeneric 11/05/2010 - "Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease." 09/01/2016 - "Newer drugs which have been shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. "
10.	Selenic AcidIBA 01/01/2017 - "Sodium selenate could be beneficial for ameliorating some symptoms that present in patients with Lafora disease." 01/01/2017 - "Sodium selenate treatment improves symptoms and seizure susceptibility in a malin-deficient mouse model of Lafora disease."

Therapies and Procedures

1.	Therapeutics 06/01/2010 - "With this protocol, we were able for the first time, to produce and purify laforin without fusion tags in the amounts traditionally needed for the crystallographic structural studies paving the way to the understanding of the molecular mechanisms of laforin activity and to the development of novel therapies for Lafora disease." 10/01/2023 - "Gys1 Antisense Therapy Prevents Disease-Driving Aggregates and Epileptiform Discharges in a Lafora Disease Mouse Model." 01/01/2022 - "Here we evaluated the effect of restoring malin in a malin-deficient mouse model of Lafora disease as a proof of concept for gene replacement therapy. " 11/29/2021 - "Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease." 10/01/2020 - "[Lafora disease in a Beagle - diagnosis and therapy]."
2.	Vagus Nerve Stimulation 03/01/2017 - "Managing Lafora body disease with vagal nerve stimulation." 01/01/2013 - "Vagus nerve stimulation in Lafora body disease." 11/01/2019 - "Super refractory status epilepticus in Lafora disease interrupted by vagus nerve stimulation: A case report."
3.	Ketogenic Diet 12/01/2020 - "Ketogenic diet reduces Lafora bodies in murine Lafora disease." 05/01/2006 - "A pilot study of a ketogenic diet in patients with Lafora body disease."
4.	Subcutaneous Injections 06/01/1987 - "Antisera against Lafora bodies were made in rabbits by subcutaneous injection of the myocardium from a patient died of Lafora disease. "