Epilepsy treatment
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- モデュライト バイオ リミテッド
- Filing Date
- 2024-05-30
- Publication Date
- 2026-06-16
Smart Images
Figure 2026519545000002 
Figure 2026519545000003 
Figure 2026519545000004
Abstract
Claims
1. A method for treating epilepsy in a person requiring it, wherein the method is (a) administering to the target thalamic nucleus a therapeutically effective dose of a polynucleotide encoding the bistability type II opsin, conjugated to a heterogeneous endoplasmic reticulum transport signal and / or membrane transport signal that enables the transport of the bistability type II opsin to the presynaptic axon terminal; and (b) Exposing the target nerve region to light of a wavelength that activates the bistable type II opsin, wherein the nerve region includes the cell body and / or the axon of the thalamic nucleus. Includes, This allows for the treatment of epilepsy in the subject, method.
2. A method for treating epilepsy in a subject in need, comprising administering a therapeutically effective amount of a polynucleotide encoding bistable type II opsin, which is conjugated to a heterogeneous endoplasmic reticulum transport signal and / or membrane transport signal that enables the transport of bistable type II opsin to presynaptic axon terminals, to the thalamic nucleus, the method comprising exposing a neural region of the subject to light of a wavelength that activates the bistable type II opsin, wherein the neural region includes the cell body and / or the axon of the thalamic nucleus, thereby treating epilepsy in the subject.
3. The method according to claim 1, wherein the epilepsy is generalized epilepsy.
4. The method according to claim 3, wherein the generalized epilepsy is selected from the group consisting of developmental epilepsy and encephalopathy (DEE), drug-resistant generalized epilepsy, Lennox-Gastaut syndrome (LGS), Dravet syndrome, epilepsy associated with mutations in Slc6a1, epilepsy associated with mutations in WWOX, generalized epilepsy of unknown cause, multifocal epilepsy, absence epilepsy, and Rasmussen syndrome.
5. The method according to claim 1, wherein the epilepsy is focal-origin epilepsy.
6. The method according to claim 5, wherein the focal-origin epilepsy is selected from the group consisting of drug-resistant focal epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, parietal lobe epilepsy, Sturge-Weber syndrome, tuberous sclerosis, post-stroke epilepsy, post-traumatic brain injury epilepsy, focal cortical dysplasia, occipital lobe epilepsy, and persistent partial epilepsy (EPC).
7. The method according to claim 5, wherein the focal-origin epilepsy includes secondary generalized seizures.
8. The method according to claim 1, wherein the administration (administering) or administration (administration) is by stereotactic injection.
9. The method according to claim 1, wherein the thalamic nuclei are selected from the group consisting of the anterior thalamic nucleus (ANT), intralaminar nuclei of the thalamus, lateral thalamic nucleus, medial thalamic nucleus, central median nucleus (CM), posterior ventral nucleus (VB), ventromedial nucleus (VM), lateral central nucleus (CL), and pulvinar.
10. The method according to claim 1, wherein the polynucleotide is encapsulated in a viral vector.
11. The method according to claim 1, wherein the nucleic acid sequence encoding the bistable type II opsin is a codon optimized for mammalian expression.
12. The method according to claim 1, wherein the bistable type II opsin is selected from the group consisting of OPN3, OPN4, OPN5, LcPP, DrPP2, TrPP2, parapinopsin, PdCO, TMT, and peropsin.
13. The method according to claim 1, wherein the bistable type II opsin is OPN3.
14. The method according to claim 13, wherein the OPN3 is mosquito OPN3 (MosOpn3).
15. The method according to claim 1, wherein the endoplasmic reticulum transport signal and / or the membrane transport signal is a protein expressed in a nerve cell.
16. The method according to claim 1, wherein the endoplasmic reticulum transport signal and / or the membrane transport signal is of a Kir2.1 polypeptide.
17. The method according to claim 1, wherein the amino acid sequence of the endoplasmic reticulum transport signal includes SEQ ID NO:
2.
18. The method according to claim 1, wherein the amino acid sequence of the membrane transport signal includes SEQ ID NO:
1.
19. The method according to claim 1, wherein the exposure is performed for at least six weeks after the administration.
20. The method according to claim 1, wherein the exposure is performed for at least eight weeks after the administration.
21. The method according to claim 1, wherein the exposure includes repeated irradiation regardless of the detection of epileptic seizures.
22. The method according to claim 1, wherein the exposure is performed when an epileptic seizure is detected.
23. The method according to claim 22, wherein the detection is performed by electrodes.
24. The method according to claim 1, wherein the exposure is performed using a skull-mounted device.
25. The method according to claim 24, wherein the skull-mounted device enables electrophysiological recording and irradiation.
26. The method according to claim 1, wherein the wavelength is 450 to 650 nm.
27. The method according to claim 1, wherein the wavelength is 350 to 670 nm.
28. The method according to claim 1, wherein the nerve region includes the thalamic region.
29. The method according to claim 1, wherein the neural region includes a cortical region.
30. The method according to claim 1, wherein the nerve region includes the presynaptic terminal of the axon.