Treatment with metformin in twelve patients with Lafora disease

Francesca Bisulli†Email author View ORCID ID profile,
Lorenzo Muccioli†,
Giuseppe d’Orsi,
Laura Canafoglia,
Elena Freri,
Laura Licchetta,
Barbara Mostacci,
Patrizia Riguzzi,
Federica Pondrelli,
Carlo Avolio,
Tommaso Martino,
Roberto Michelucci and
Paolo Tinuper

†Contributed equally

Orphanet Journal of Rare Diseases201914:149

https://doi.org/10.1186/s13023-019-1132-3

Received: 11 April 2019
Accepted: 12 June 2019
Published: 21 June 2019

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.