Lafora_Disease

1. Disease Information

1.1 Definition and current understanding

LD is described in recent literature as a “rare, autosomal recessive neurodegenerative disorder” and a “progressive myoclonus epilepsy” with disrupted glycogen metabolism and “pathognomonic… Lafora bodies.” (aggradi2023laforadiseasea pages 1-2)

Abstract-supported definition quotes (recent): - “Lafora disease is a rare genetic disorder characterized by a disruption in glycogen metabolism. It manifests as progressive myoclonus epilepsy and cognitive decline during adolescence.” (Dec 2023; Brain Sciences) (aggradi2023laforadiseasea pages 1-2) - “Background Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1.” (Sep 2023; Orphanet J Rare Dis) (pondrelli2023prognosticvalueof pages 1-2)

1.2 Key identifiers, synonyms, and data provenance

The retrieved evidence directly supports MONDO and OMIM identifiers; other identifier systems (Orphanet/MeSH/ICD) were not captured in the retrieved sources.

Table: This table summarizes key disease identifiers and naming information for Lafora disease using only retrieved evidence. It highlights confirmed MONDO and OMIM identifiers and clearly marks systems not directly captured in the available sources.

Common synonyms/alternative names (supported in retrieved sources): - “Lafora disease” and “progressive myoclonus epilepsy” (PME) framing (aggradi2023laforadiseasea pages 1-2, zimmern2024progressivemyoclonusepilepsy pages 6-7) - Genetic subtypes: “myoclonic epilepsy of Lafora 1/2” appear as MONDO entities in Open Targets (MONDO_0958199; MONDO_0800306), reflecting EPM2A vs NHLRC1 subtypes (Open Targets output embedded in evidence stream; disease MONDO confirmed) (aggradi2023laforadiseasea pages 1-2)

Evidence type note: This report primarily uses aggregated disease-level resources (systematic review/meta-analysis; scoping review; ClinicalTrials.gov records) plus patient-level case report evidence and multiple model organism studies. (pondrelli2023prognosticvalueof pages 1-2, aggradi2023laforadiseasea pages 1-2, NCT03876522 chunk 1)

2. Etiology

2.1 Disease causal factors

LD is a Mendelian disorder caused by loss-of-function biallelic pathogenic variants in: - EPM2A → laforin (glucan phosphatase/dual-specificity phosphatase) (pondrelli2023prognosticvalueof pages 1-2, donohue2023gys1antisensetherapy pages 1-2) - NHLRC1 (EPM2B) → malin (E3 ubiquitin ligase) (pondrelli2023prognosticvalueof pages 1-2, donohue2023gys1antisensetherapy pages 1-2)

Mechanistic genetic etiology: laforin and malin regulate glycogen metabolism and prevent conversion of soluble glycogen into insoluble polyglucosan aggregates (Lafora bodies). (pondrelli2023prognosticvalueof pages 1-2, duran2023roleofastrocytes pages 2-4)

2.2 Genetic risk factors (causal variants)

A 2023 systematic review/meta-analysis (patient-level) compiled 250 genetically confirmed cases and characterized variant classes and prognostic correlations. (pondrelli2023prognosticvalueof pages 1-2)

Table: This table summarizes the two established causal genes for Lafora disease, their protein products, inheritance, variant classes, and the main genotype–phenotype findings from the 2023 patient-level meta-analysis. It is useful as a compact reference for disease-gene annotation and prognostic interpretation.

Key statistics from the 2023 meta-analysis: - 250 cases from 70 articles; 114 pathogenic variants total (67 EPM2A, 47 NHLRC1) (pondrelli2023prognosticvalueof pages 1-2) - Gene distribution: NHLRC1 in ~56% vs EPM2A in ~44% (pondrelli2023prognosticvalueof pages 2-4, zimmern2024progressivemyoclonusepilepsy pages 6-7) - Prognosis: NHLRC1 PT/PT genotype associated with shorter survival (HR 2.88, 95% CI 1.23–6.78) (pondrelli2023prognosticvalueof pages 1-2)

2.3 Non-genetic risk/protective factors; gene–environment interaction

No specific environmental risk factors, protective factors, or gene–environment interactions were captured in the retrieved evidence. In the current understanding from retrieved sources, LD is primarily driven by genetic disruption of glycogen homeostasis and secondary neuroinflammation. (duran2023roleofastrocytes pages 2-4, rubio2024beneficialeffectof pages 1-2)

3. Phenotypes

3.1 Core phenotype spectrum (human)

Clinical features described in recent clinical literature include: - Progressive myoclonic epilepsy: generalized tonic–clonic seizures, myoclonic jerks/spasms; visual phenomena/seizures can occur (aggradi2023laforadiseasea pages 1-2, aggradi2023laforadiseasea pages 4-6) - Progressive cognitive decline/dementia and neuropsychiatric symptoms (aggradi2023laforadiseasea pages 1-2, aggradi2023laforadiseasea pages 4-6) - Ataxia and other cerebellar signs may appear (aggradi2023laforadiseasea pages 4-6, zimmern2024progressivemyoclonusepilepsy pages 6-7)

Abstract quote (clinical): “It manifests as progressive myoclonus epilepsy and cognitive decline during adolescence.” (aggradi2023laforadiseasea pages 1-2)

3.2 Phenotype characteristics (onset, progression, severity)

• Typical onset: adolescence; Italian cohort mean onset 13.4 years (zimmern2024progressivemyoclonusepilepsy pages 6-7)
• Rapidly progressive course: cognitive decline commonly emerges 2–6 years after onset in one review/case synthesis (aggradi2023laforadiseasea pages 4-6)
• Fatal outcome: often within ~10 years of onset (multiple recent sources; also expressed as 5–10 years after onset) (aggradi2023laforadiseasea pages 4-6, duran2023roleofastrocytes pages 1-2)

3.3 Natural history statistics and prognosis

From a large Italian natural-history cohort summarized in a 2024 PME scoping review: - Survival: 93% at 5 years, 62% at 10 years, 57% at 15 years (zimmern2024progressivemyoclonusepilepsy pages 6-7) - Median time to loss of autonomy: 6 years (zimmern2024progressivemyoclonusepilepsy pages 6-7) - Median survival: 11 years (zimmern2024progressivemyoclonusepilepsy pages 6-7)

From a 2023 patient-level meta-analysis (subset statistics reported): for EPM2A cases, “overall survival was 92% at 5 years, 59% at 10 years, and 49% at 15 years (mean age at death 22.4 years).” (pondrelli2023prognosticvalueof pages 2-4)

3.4 Suggested HPO terms (not exhaustive)

Based on the retrieved phenotype descriptions: - Seizures: HP:0001250 (Seizures); generalized tonic–clonic seizures HP:0002069 - Myoclonus: HP:0001336 (Myoclonus) - Progressive cognitive decline/dementia: HP:0001268 (Mental deterioration); dementia HP:0000726 - Ataxia: HP:0001251 (Ataxia) - Dysarthria: HP:0001260 (Dysarthria) (aggradi2023laforadiseasea pages 2-4) - Dysphagia: HP:0002015 (Dysphagia) (aggradi2023laforadiseasea pages 2-4)

Frequency-by-phenotype was not available in the retrieved excerpts; cohort-level frequency extraction would require additional full-text/registry sources.

4. Genetic/Molecular Information

4.1 Causal genes and variant architecture

LD is caused by biallelic pathogenic variants in EPM2A or NHLRC1/EPM2B. (pondrelli2023prognosticvalueof pages 1-2, donohue2023gys1antisensetherapy pages 1-2)

Variant architecture highlights: - Extreme allelic heterogeneity: “More than 150 different causative genetic variants” reported (pondrelli2023prognosticvalueof pages 1-2) - Variant types: missense/in-frame vs protein truncating (nonsense/frameshift/splice/deletions) (pondrelli2023prognosticvalueof pages 2-4)

4.2 Functional consequences (protein dysfunction)

• Laforin deficiency affects glycogen phosphate homeostasis and/or glycogen architecture; malin deficiency disrupts regulation of glycogen-related proteins (e.g., PTG) and contributes to abnormal glycogen accumulation (mitra2023laforintargetsmalin pages 10-10, duran2023roleofastrocytes pages 8-10)

4.3 Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes, epigenetic mechanisms, or chromosomal abnormalities were captured in the retrieved evidence.

5. Environmental Information

No non-genetic environmental, lifestyle, or infectious causes were captured in the retrieved evidence, consistent with LD being a primarily genetic neurodegenerative epilepsy syndrome in these sources. (pondrelli2023prognosticvalueof pages 1-2)

6. Mechanism / Pathophysiology

6.1 Causal chain (current model)

A synthesis consistent across 2023–2024 sources: 1. Biallelic EPM2A or NHLRC1 variants → loss of laforin/malin complex function (pondrelli2023prognosticvalueof pages 1-2, duran2023roleofastrocytes pages 2-4) 2. Dysregulated glycogen metabolism → abnormal glycogen chain length/branching (and in some models hyperphosphorylation) → “transition of soluble glycogen to insoluble polyglucosan” (duran2023roleofastrocytes pages 8-10, mitra2023laforintargetsmalin pages 1-2) 3. Formation of Lafora bodies (polyglucosan aggregates) containing glycogen metabolism proteins and proteostasis/adaptor proteins including GS, ubiquitin, p62 (duran2023roleofastrocytes pages 1-2, duran2023roleofastrocytes pages 2-4) 4. Predominant accumulation in astrocytes (with neuronal inclusions also present) → network dysfunction, neuroinflammation, progressive seizures and neurodegeneration (duran2023roleofastrocytes pages 1-2, duran2023roleofastrocytes pages 2-4)

Abstract quote (astrocyte emphasis): “However, it was recently identified that most of these glycogen aggregates are present in astrocytes. Importantly, astrocytic Lafora bodies have been shown to contribute to pathology in Lafora disease.” (Feb 2023; Cells) (duran2023roleofastrocytes pages 1-2)

6.2 Cellular processes and pathways

• Autophagy/endolysosomal dysfunction: LD inclusions and associated proteins implicate autophagic handling; autophagy impairment is described as secondary to glycogen accumulation and normalizes when glycogen accumulation is prevented in models (duran2023roleofastrocytes pages 2-4, duran2023roleofastrocytes pages 10-11)
• Neuroinflammation: reactive astrocytes/microglia are described; a 2024 Epm2b-/- mouse study identified inflammatory pathway involvement including “mainly TNF and IL-6 signaling pathways” and demonstrated infiltration of peripheral immune cells (T-lymphocytes) (rubio2024beneficialeffectof pages 1-2)

6.3 Anatomical and cell-type localization

• Lafora bodies accumulate in brain and peripheral tissues (e.g., liver, muscle, sweat glands) (aggradi2023laforadiseasea pages 4-6)
• Cell types: both neuronal and astrocytic inclusions; “most LBs are present in astrocytes” with distinct morphologies (neuronal perinuclear nLBs vs corpora-amylacea-like astrocytic bodies) (duran2023roleofastrocytes pages 2-4)

6.4 Suggested ontology terms

GO biological process (examples): - Glycogen metabolic process (GO:0005977) - Glycogen biosynthetic process (GO:0005978) - Macroautophagy (GO:0016236) - Neuroinflammatory response (GO:0150076)

Cell Ontology (CL) suggestions: - Astrocyte (CL:0000127) - Neuron (CL:0000540) - Microglial cell (CL:0000129) - T cell (CL:0000084)

7. Anatomical Structures Affected

7.1 Organ/tissue systems

• Central nervous system (primary): progressive epilepsy, cognitive decline, neurodegeneration (zimmern2024progressivemyoclonusepilepsy pages 6-7)
• Peripheral tissues: Lafora bodies may be found in “brain, liver, muscle, and sweat glands” (aggradi2023laforadiseasea pages 4-6)

7.2 Suggested UBERON terms (examples)

• Brain (UBERON:0000955)
• Hippocampus (LBs enriched in astrocytes notably in hippocampus per review) (UBERON:0001954) (duran2023roleofastrocytes pages 2-4)
• Skeletal muscle tissue (UBERON:0001134)
• Skin (sweat glands/ducts) (UBERON:0002097)

8. Temporal Development

• Onset: typically adolescence; previously healthy children develop seizures (duran2023roleofastrocytes pages 1-2)
• Progression: progressive, rapid; median loss of autonomy 6 years and median survival 11 years (zimmern2024progressivemyoclonusepilepsy pages 6-7)

No remission patterns were captured in the retrieved evidence.

9. Inheritance and Population

9.1 Inheritance

Autosomal recessive, due to biallelic variants in EPM2A or NHLRC1. (pondrelli2023prognosticvalueof pages 1-2)

9.2 Epidemiology and geographic distribution

Prevalence estimates in retrieved sources: - “approximately four cases per one million individuals” (aggradi2023laforadiseasea pages 1-2) - Germany: 1.69 per 10 million (zimmern2024progressivemyoclonusepilepsy pages 6-7)

Geographic concentration (qualitative): “occurs most frequently in Mediterranean countries, South India, North Africa, and the Middle East.” (aggradi2023laforadiseasea pages 1-2)

Population-genetic details not captured in retrieved excerpts: incidence, carrier frequency, sex ratio, and explicit consanguinity rates.

10. Diagnostics

10.1 Clinical and electrophysiology

EEG findings include generalized/multifocal epileptiform discharges; in one case report EEG showed “multiple discharges across both brain hemispheres.” (aggradi2023laforadiseasea pages 1-2)

The 2024 scoping review highlights characteristic electrophysiology (photo-paroxysmal response, giant SSEP) though milder genotypes may show these less often. (zimmern2024progressivemyoclonusepilepsy pages 6-7)

10.2 Neuroimaging

MRI can be normal early: “Brain magnetic resonance imaging was unremarkable” in a genetically confirmed case (aggradi2023laforadiseasea pages 1-2); later disease may show widespread degeneration (aggradi2023laforadiseasea pages 4-6)

10.3 Biopsy

• Axillary skin biopsy can detect PAS-positive inclusions in sweat duct cells but has “false-positive/false-negative limitations” (diagnostic pitfalls). (aggradi2023laforadiseasea pages 4-6)
• Muscle biopsy may be atypical or lack Lafora bodies (as in a confirmed NHLRC1 case). (aggradi2023laforadiseasea pages 1-2, aggradi2023laforadiseasea pages 2-4)

10.4 Genetic testing

Genetic confirmation requires identifying biallelic pathogenic variants in EPM2A or EPM2B/NHLRC1; a case report used targeted NGS (clinical exome) plus Sanger confirmation and parental testing, with ACMG classification. (aggradi2023laforadiseasea pages 1-2, aggradi2023laforadiseasea pages 2-4)

10.5 Differential diagnosis

LD should be considered among progressive, refractory myoclonic epilepsies in children/young adults, and overlapping polyglucosan storage disorders are part of the differential. (aggradi2023laforadiseasea pages 1-2, aggradi2023laforadiseasea pages 6-7)

11. Outcome / Prognosis

LD is severe and progressive with high morbidity and premature mortality. Key quantitative outcomes from natural history are summarized above (Section 3.3). Prognosis can vary by genotype; truncating NHLRC1 genotypes are associated with shorter survival in the patient-level meta-analysis, and NHLRC1 p.Asp146Asn is associated with a more favorable course. (pondrelli2023prognosticvalueof pages 1-2, zimmern2024progressivemyoclonusepilepsy pages 6-7)

12. Treatment

12.1 Current clinical management (supportive)

There is no established disease-modifying therapy in routine practice in the retrieved sources. Management is supportive and symptom-focused (seizure control, supportive care), with diet-based interventions historically explored. (aggradi2023laforadiseasea pages 1-2, NCT00007124 chunk 1)

12.2 Experimental / translational therapeutics (2023–2024 emphasis)

A major contemporary strategy is substrate reduction—reducing glycogen synthesis in brain to prevent polyglucosan/Lafora body formation.

Table: This table summarizes the main retrieved Lafora disease clinical studies, expanded-access programs, and leading 2023–2024 preclinical therapeutic strategies. It is useful for quickly comparing mechanisms, populations/models, endpoints, and development status across the current translational landscape.

Key 2023–2024 developments from retrieved evidence: - GYS1 antisense (preclinical): intracerebroventricular Gys1-ASO at 4/7/10 months reduced Gys1 protein and Lafora body burden and reduced epileptiform discharges in Epm2b-/- mice (donohue2023gys1antisensetherapy pages 4-6) - ION283 (clinical trial): intrathecal ASO trial uses EEG biomarkers over 2 years as efficacy endpoints; recruiting ages 10–18 (NCT06609889) (NCT06609889 chunk 2) - Neuroinflammation modulation (preclinical): fingolimod reduced reactive astrocyte-derived neuroinflammation and T-lymphocyte infiltration and improved behavior in Epm2b-/- mice; inflammatory signaling implicated includes TNF and IL-6 (rubio2024beneficialeffectof pages 1-2, rubio2024beneficialeffectof pages 2-4) - VAL-1221 expanded access: IV 20 mg/kg every other week, up to 10 patients, genetically confirmed mid-stage disease (NCT05930223) (NCT05930223 chunk 1)

12.3 Suggested MAXO terms (examples)

• Antisense oligonucleotide therapy (MAXO term family; label: antisense therapy)
• Ketogenic diet therapy (dietary therapy)
• Expanded access treatment program
• Gene therapy / gene replacement therapy (preclinical in retrieved sources) (zafrapuerta2023genereplacementtherapy pages 21-24)

Specific MAXO IDs were not captured in retrieved sources; mapping would require ontology lookup.

13. Prevention

No primary prevention strategies beyond genetic counseling and family planning are detailed in retrieved sources. Genetic confirmation and family testing are implied by autosomal recessive inheritance and use of parental testing in case reports. (aggradi2023laforadiseasea pages 2-4)

14. Other Species / Natural Disease

Naturally occurring Lafora-like disease has been described in dogs and linked to NHLRC1 repeat expansions, including an “NHLRC1 repeat expansion in two beagles” and an “NHLRC1 homozygous dodecamer expansion in a Newfoundland dog,” with reports spanning multiple breeds (e.g., Basset hound, beagle, Newfoundland dog, miniature Wirehaired Dachshunds). (vincent2023retinalphenotypingof pages 9-10)

15. Model Organisms

15.1 Mammalian models (mouse)

Common murine models include Epm2a−/− (laforin KO) and Epm2b−/− (malin KO), which develop Lafora bodies and neurological phenotypes and are used for therapy testing (ASO, gene replacement). (donohue2023gys1antisensetherapy pages 1-2, zafrapuerta2023genereplacementtherapy pages 1-4)

Retinal biomarker/endpoint development (quantitative): In Epm2a−/− mice, retinal PASD staining showed inner plexiform layer Lafora body density 1743 ± 533/mm² at 10 months and 2615 ± 915/mm² at 14 months, while ERG parameters and retinal thickness were preserved, supporting retinal LB quantification as a potential monitoring readout in mice. (vincent2023retinalphenotypingof pages 1-2)

Neuromuscular model phenotype (2024): Laforin-deficient mice show neuromuscular junction dysfunction and motor neuron loss with an electrophysiological decrement reported as “(14.93±4.26%) at 50 Hz at the age of 5 months.” (shukla2024neuromuscularjunctiondysfunction pages 1-2)

15.2 Invertebrate models

A 2023 mechanistic review cites Drosophila and indicates forced neuronal glycogen accumulation can cause neuronal apoptosis, supporting glycogen excess as a driver of neurodegeneration. (duran2023roleofastrocytes pages 2-4)

Recent developments and expert analysis (2023–2024 priority)

1. Genotype–prognosis associations were quantitatively strengthened by a 2023 patient-level meta-analysis showing truncating NHLRC1 genotypes predict worse survival (HR 2.88), which is directly relevant for stratification and interpretation of disease-modifying trials. (pondrelli2023prognosticvalueof pages 1-2)
2. Cell-type re-framing toward astrocytes: a 2023 review emphasized that “most” Lafora bodies are astrocytic and that astrocytic aggregates contribute to pathology, shifting mechanistic and therapeutic attention to glial glycogen metabolism and glia-driven inflammation. (duran2023roleofastrocytes pages 1-2, duran2023roleofastrocytes pages 2-4)
3. Translational pipeline maturity: the existence of an Ionis-sponsored natural history study (NCT03876522) defining outcome measures and biomarkers, plus a recruiting ASO trial (NCT06609889) with EEG endpoints, indicates field movement from preclinical substrate reduction to biomarker-driven clinical development. (NCT03876522 chunk 1, NCT06609889 chunk 2)

Data gaps and limitations (from retrieved sources)

• Orphanet/MeSH/ICD identifiers were not captured in retrieved evidence.
• Incidence, carrier frequency, sex ratio, and explicit consanguinity statistics were not available in the retrieved excerpts.
• Phenotype frequencies (percent affected) for individual HPO terms were not extractable from the retrieved excerpts; fuller cohort papers would be needed.

Key resources (URLs; access dates not applicable)

• Open Targets disease page (MONDO_0009697): https://platform.opentargets.org/disease/MONDO_0009697 (aggradi2023laforadiseasea pages 1-2)
• OMIM entry #254780: https://omim.org/entry/254780 (aggradi2023laforadiseasea pages 1-2)
• Pondrelli et al., 2023 (Orphanet J Rare Dis; DOI 10.1186/s13023-023-02880-6): https://doi.org/10.1186/s13023-023-02880-6 (pondrelli2023prognosticvalueof pages 1-2)
• Zimmern & Minassian, 2024 (Genes; DOI 10.3390/genes15020171): https://doi.org/10.3390/genes15020171 (zimmern2024progressivemyoclonusepilepsy pages 6-7)
• Donohue et al., 2023 (Neurotherapeutics; DOI 10.1007/s13311-023-01434-9): https://doi.org/10.1007/s13311-023-01434-9 (donohue2023gys1antisensetherapy pages 4-6)
• Duran, 2023 (Cells; DOI 10.3390/cells12050722): https://doi.org/10.3390/cells12050722 (duran2023roleofastrocytes pages 1-2)
• Rubio et al., 2024 (Molecular Neurobiology; DOI 10.1007/s12035-023-03766-1): https://doi.org/10.1007/s12035-023-03766-1 (rubio2024beneficialeffectof pages 1-2)
• ClinicalTrials.gov: NCT06609889 https://clinicaltrials.gov/study/NCT06609889 ; NCT03876522 https://clinicaltrials.gov/study/NCT03876522 ; NCT05930223 https://clinicaltrials.gov/study/NCT05930223 ; NCT00007124 https://clinicaltrials.gov/study/NCT00007124 (NCT06609889 chunk 2, NCT03876522 chunk 1, NCT05930223 chunk 1, NCT00007124 chunk 1)

References

1. (aggradi2023laforadiseasea pages 1-2): Carola Rita Ferrari Aggradi, Martina Rimoldi, Gloria Romagnoli, Daniele Velardo, Megi Meneri, Davide Iacobucci, Michela Ripolone, Laura Napoli, Patrizia Ciscato, Maurizio Moggio, Giacomo Pietro Comi, Dario Ronchi, Stefania Corti, and Elena Abati. Lafora disease: a case report and evolving treatment advancements. Brain Sciences, 13:1679, Dec 2023. URL: https://doi.org/10.3390/brainsci13121679, doi:10.3390/brainsci13121679. This article has 8 citations.

2. (pondrelli2023prognosticvalueof pages 1-2): Federica Pondrelli, Raffaella Minardi, Lorenzo Muccioli, Corrado Zenesini, Luca Vignatelli, Laura Licchetta, Barbara Mostacci, Paolo Tinuper, Craig W. Vander Kooi, Matthew S. Gentry, and Francesca Bisulli. Prognostic value of pathogenic variants in lafora disease: systematic review and meta-analysis of patient-level data. Orphanet Journal of Rare Diseases, Sep 2023. URL: https://doi.org/10.1186/s13023-023-02880-6, doi:10.1186/s13023-023-02880-6. This article has 16 citations and is from a peer-reviewed journal.

3. (NCT06609889 chunk 2): Berge Minassian. A Safety and Efficacy of Intrathecally Administered ION283 in Patients With Lafora Disease. Berge Minassian. 2024. ClinicalTrials.gov Identifier: NCT06609889

4. (zimmern2024progressivemyoclonusepilepsy pages 6-7): Vincent Zimmern and Berge Minassian. Progressive myoclonus epilepsy: a scoping review of diagnostic, phenotypic and therapeutic advances. Genes, 15:171, Jan 2024. URL: https://doi.org/10.3390/genes15020171, doi:10.3390/genes15020171. This article has 20 citations.

5. (rubio2024beneficialeffectof pages 1-2): Teresa Rubio, Ángela Campos-Rodríguez, and Pascual Sanz. Beneficial effect of fingolimod in a lafora disease mouse model by preventing reactive astrogliosis-derived neuroinflammation and brain infiltration of t-lymphocytes. Molecular Neurobiology, 61:3105-3120, Nov 2024. URL: https://doi.org/10.1007/s12035-023-03766-1, doi:10.1007/s12035-023-03766-1. This article has 5 citations and is from a peer-reviewed journal.

6. (NCT03876522 chunk 1): Natural History and Functional Status Study of Patients With Lafora Disease. Ionis Pharmaceuticals, Inc.. 2019. ClinicalTrials.gov Identifier: NCT03876522

7. (donohue2023gys1antisensetherapy pages 1-2): Katherine J. Donohue, Bethany Fitzsimmons, Ronald C. Bruntz, Kia H. Markussen, Lyndsay E.A. Young, Harrison A. Clarke, Peyton T. Coburn, Laiken E. Griffith, William Sanders, Jack Klier, Sara N. Burke, Andrew P. Maurer, Berge A. Minassian, Ramon C. Sun, Holly B. Kordasiewisz, and Matthew S. Gentry. Gys1 antisense therapy prevents disease-driving aggregates and epileptiform discharges in a lafora disease mouse model. Neurotherapeutics, 20:1808-1819, Oct 2023. URL: https://doi.org/10.1007/s13311-023-01434-9, doi:10.1007/s13311-023-01434-9. This article has 18 citations and is from a peer-reviewed journal.

8. (duran2023roleofastrocytes pages 2-4): Jordi Duran. Role of astrocytes in the pathophysiology of lafora disease and other glycogen storage disorders. Cells, 12:722, Feb 2023. URL: https://doi.org/10.3390/cells12050722, doi:10.3390/cells12050722. This article has 9 citations.

9. (pondrelli2023prognosticvalueof pages 2-4): Federica Pondrelli, Raffaella Minardi, Lorenzo Muccioli, Corrado Zenesini, Luca Vignatelli, Laura Licchetta, Barbara Mostacci, Paolo Tinuper, Craig W. Vander Kooi, Matthew S. Gentry, and Francesca Bisulli. Prognostic value of pathogenic variants in lafora disease: systematic review and meta-analysis of patient-level data. Orphanet Journal of Rare Diseases, Sep 2023. URL: https://doi.org/10.1186/s13023-023-02880-6, doi:10.1186/s13023-023-02880-6. This article has 16 citations and is from a peer-reviewed journal.

10. (aggradi2023laforadiseasea pages 4-6): Carola Rita Ferrari Aggradi, Martina Rimoldi, Gloria Romagnoli, Daniele Velardo, Megi Meneri, Davide Iacobucci, Michela Ripolone, Laura Napoli, Patrizia Ciscato, Maurizio Moggio, Giacomo Pietro Comi, Dario Ronchi, Stefania Corti, and Elena Abati. Lafora disease: a case report and evolving treatment advancements. Brain Sciences, 13:1679, Dec 2023. URL: https://doi.org/10.3390/brainsci13121679, doi:10.3390/brainsci13121679. This article has 8 citations.

11. (duran2023roleofastrocytes pages 1-2): Jordi Duran. Role of astrocytes in the pathophysiology of lafora disease and other glycogen storage disorders. Cells, 12:722, Feb 2023. URL: https://doi.org/10.3390/cells12050722, doi:10.3390/cells12050722. This article has 9 citations.

12. (aggradi2023laforadiseasea pages 2-4): Carola Rita Ferrari Aggradi, Martina Rimoldi, Gloria Romagnoli, Daniele Velardo, Megi Meneri, Davide Iacobucci, Michela Ripolone, Laura Napoli, Patrizia Ciscato, Maurizio Moggio, Giacomo Pietro Comi, Dario Ronchi, Stefania Corti, and Elena Abati. Lafora disease: a case report and evolving treatment advancements. Brain Sciences, 13:1679, Dec 2023. URL: https://doi.org/10.3390/brainsci13121679, doi:10.3390/brainsci13121679. This article has 8 citations.

13. (mitra2023laforintargetsmalin pages 10-10): Sharmistha Mitra, Baozhi Chen, Peixiang Wang, Erin E. Chown, Mathew Dear, Dikran R. Guisso, Ummay Mariam, Jun Wu, Emrah Gumusgoz, and Berge A. Minassian. Laforin targets malin to glycogen in lafora progressive myoclonus epilepsy. Disease Models & Mechanisms, Jan 2023. URL: https://doi.org/10.1242/dmm.049802, doi:10.1242/dmm.049802. This article has 19 citations and is from a domain leading peer-reviewed journal.

14. (duran2023roleofastrocytes pages 8-10): Jordi Duran. Role of astrocytes in the pathophysiology of lafora disease and other glycogen storage disorders. Cells, 12:722, Feb 2023. URL: https://doi.org/10.3390/cells12050722, doi:10.3390/cells12050722. This article has 9 citations.

15. (mitra2023laforintargetsmalin pages 1-2): Sharmistha Mitra, Baozhi Chen, Peixiang Wang, Erin E. Chown, Mathew Dear, Dikran R. Guisso, Ummay Mariam, Jun Wu, Emrah Gumusgoz, and Berge A. Minassian. Laforin targets malin to glycogen in lafora progressive myoclonus epilepsy. Disease Models & Mechanisms, Jan 2023. URL: https://doi.org/10.1242/dmm.049802, doi:10.1242/dmm.049802. This article has 19 citations and is from a domain leading peer-reviewed journal.

16. (duran2023roleofastrocytes pages 10-11): Jordi Duran. Role of astrocytes in the pathophysiology of lafora disease and other glycogen storage disorders. Cells, 12:722, Feb 2023. URL: https://doi.org/10.3390/cells12050722, doi:10.3390/cells12050722. This article has 9 citations.

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