Abstract
Background: Lafora disease (LD) is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Studies on a mouse model of LD showed a good response to metformin, a drug with a well known neuroprotective effect. For this reason, in 2016, the European Medicines Agency granted orphan designation to metformin for the treatment of LD. However, no clinical data is available thus far. Methods: We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. Results: Twelve patients with genetically confirmed LD (6 EPM2A, 6 NHLRC1) at middle/late stages of disease were treated with add-on metformin for a mean period of 18 months (range: 6-36). Metformin was titrated to a mean maintenance dose of 1167 mg/day (range: 500-2000 mg). In four patients dosing was limited by gastrointestinal side-effects. No serious adverse events occurred. Three patients had a clinical response, which was temporary in two, characterized by a reduction of seizure frequency and global clinical improvement. Conclusions: Metformin was overall safe in our small cohort of LD patients. Even though the clinical outcome was poor, this may be related to the advanced stage of disease in our cases and we cannot exclude a role of metformin in slowing down LD progression. Therefore, on the grounds of the preclinical data, we believe that treatment with metformin may be attempted as early as possible in the course of LD.
| Original language | English |
|---|---|
| Article number | 149 |
| Journal | Orphanet Journal of Rare Diseases |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jun 21 2019 |
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Keywords
- EPM2A
- EPM2B
- Lafora disease
- Metformin
- NHLRC1
- Progressive myoclonus epilepsy
ASJC Scopus subject areas
- Genetics(clinical)
- Pharmacology (medical)
Cite this
Treatment with metformin in twelve patients with Lafora disease. / Bisulli, Francesca; Muccioli, Lorenzo; D'Orsi, Giuseppe; Canafoglia, Laura; Freri, Elena; Licchetta, Laura; Mostacci, Barbara; Riguzzi, Patrizia; Pondrelli, Federica; Avolio, Carlo; Martino, Tommaso; Michelucci, Roberto; Tinuper, Paolo.
In: Orphanet Journal of Rare Diseases, Vol. 14, No. 1, 149, 21.06.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Treatment with metformin in twelve patients with Lafora disease
AU - Bisulli, Francesca
AU - Muccioli, Lorenzo
AU - D'Orsi, Giuseppe
AU - Canafoglia, Laura
AU - Freri, Elena
AU - Licchetta, Laura
AU - Mostacci, Barbara
AU - Riguzzi, Patrizia
AU - Pondrelli, Federica
AU - Avolio, Carlo
AU - Martino, Tommaso
AU - Michelucci, Roberto
AU - Tinuper, Paolo
N1 - Ricercatori distaccati presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Bisulli Francesca, Licchetta Laura, Tinuper Paolo).
PY - 2019/6/21
Y1 - 2019/6/21
N2 - Background: Lafora disease (LD) is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Studies on a mouse model of LD showed a good response to metformin, a drug with a well known neuroprotective effect. For this reason, in 2016, the European Medicines Agency granted orphan designation to metformin for the treatment of LD. However, no clinical data is available thus far. Methods: We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. Results: Twelve patients with genetically confirmed LD (6 EPM2A, 6 NHLRC1) at middle/late stages of disease were treated with add-on metformin for a mean period of 18 months (range: 6-36). Metformin was titrated to a mean maintenance dose of 1167 mg/day (range: 500-2000 mg). In four patients dosing was limited by gastrointestinal side-effects. No serious adverse events occurred. Three patients had a clinical response, which was temporary in two, characterized by a reduction of seizure frequency and global clinical improvement. Conclusions: Metformin was overall safe in our small cohort of LD patients. Even though the clinical outcome was poor, this may be related to the advanced stage of disease in our cases and we cannot exclude a role of metformin in slowing down LD progression. Therefore, on the grounds of the preclinical data, we believe that treatment with metformin may be attempted as early as possible in the course of LD.
AB - Background: Lafora disease (LD) is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Studies on a mouse model of LD showed a good response to metformin, a drug with a well known neuroprotective effect. For this reason, in 2016, the European Medicines Agency granted orphan designation to metformin for the treatment of LD. However, no clinical data is available thus far. Methods: We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. Results: Twelve patients with genetically confirmed LD (6 EPM2A, 6 NHLRC1) at middle/late stages of disease were treated with add-on metformin for a mean period of 18 months (range: 6-36). Metformin was titrated to a mean maintenance dose of 1167 mg/day (range: 500-2000 mg). In four patients dosing was limited by gastrointestinal side-effects. No serious adverse events occurred. Three patients had a clinical response, which was temporary in two, characterized by a reduction of seizure frequency and global clinical improvement. Conclusions: Metformin was overall safe in our small cohort of LD patients. Even though the clinical outcome was poor, this may be related to the advanced stage of disease in our cases and we cannot exclude a role of metformin in slowing down LD progression. Therefore, on the grounds of the preclinical data, we believe that treatment with metformin may be attempted as early as possible in the course of LD.
KW - EPM2A
KW - EPM2B
KW - Lafora disease
KW - Metformin
KW - NHLRC1
KW - Progressive myoclonus epilepsy
UR - http://www.scopus.com/inward/record.url?scp=85068510737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068510737&partnerID=8YFLogxK
U2 - 10.1186/s13023-019-1132-3
DO - 10.1186/s13023-019-1132-3
M3 - Article
C2 - 31227012
AN - SCOPUS:85068510737
VL - 14
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 149
ER -