Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment.
Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.
Inserm, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000 Grenoble, France.
F
F
Studer
Inserm, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000 Grenoble, France.
R
R
Serduc
SynapCell SAS, 38700 La Tronche, France.
B
B
Pouyatos
Inserm, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000 Grenoble, France.
T
T
Chabrol
European Synchrotron Research Facility, Biomedical Beamline ID17, Grenoble, France.
E
E
Bräuer-Krisch
European Synchrotron Research Facility, Biomedical Beamline ID17, Grenoble, France.
M
M
Donzelli
European Synchrotron Research Facility, Biomedical Beamline ID17, Grenoble, France.
C
C
Nemoz
University of Bern, Switzerland.
J A
JA
Laissue
Inserm, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000 Grenoble, France; CHU de Grenoble, F-38000 Grenoble, France.
F
F
Estève
Inserm, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, F-38000 Grenoble, France; CHU de Grenoble, F-38000 Grenoble, France. Electronic address: antoine.depaulis@ujf-grenoble.fr.
A
A
Depaulis
D000818:Animals; D001683:Biological Clocks; D019583:Dose Fractionation, Radiation; D000069279:Drug Resistant Epilepsy / Q000503:physiopathology* / Q000601:surgery*; D004867:Equipment Design; D005240:Feasibility Studies; D006624:Hippocampus / Q000503:physiopathology / Q000528:radiation effects / Q000601:surgery; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000503:physiopathology / Q000601:surgery; D016634:Radiosurgery / Q000295:instrumentation* / Q000379:methods; D011882:Radiotherapy, High-Energy / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017356:Synchrotrons / Q000295:instrumentation*; D016896:Treatment Outcome
Animal models; Epilepsy; Radiosurgery; Synchrotron X-ray microbeams