Neuropeptide-expressing vectors and methods for the treatment of epilepsy

A method for treating epilepsy comprising:

• administering a delivery vector which provides activation of human Kappa Opioid receptors in the epileptogenic focus,
• wherein the delivery vector comprises a DNA sequence comprising a sequence that encodes preprodynorphin or a preprodynorphin variant, wherein said sequence that encodes preprodynorphin or a preprodynorphin variant comprises a signal sequence that encodes a signal peptide,
• wherein said pre-prodynorphin or pre-prodynorphin-variant comprises at least one of the following sequences:
• a. Dyn A that is SEQ ID No. 7 (AA 207-223 of SEQ ID No. 1;
• ppDyn) or a variant thereof consisting of the first 13 AA (first from the N-terminal end) or a variant thereof consisting of the first 8 AA (first from the N-terminal end);
• b. Dyn B that is SEQ ID No. 8 (AA 226-238 of SEQ ID No. 1;
• ppDyn);
• c. leumorphin that is SEQ ID No. 9 (AA 226-254 of SEQ ID No. 1;
• ppDyn);
• d. variants of Dyn A according to SEQ ID No. 7 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 7 (YGGFLRRI (SEQ ID NO:
• 18));
• e. variants of Dyn B according to SEQ ID No. 8 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 8 (YGGFLRRQ (SEQ ID NO:
• 19));
• f. variants of leumorphin according to SEQ ID No. 9 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 9 (YGGFLRRQ (SEQ ID NO:
• 19));
• g. SEQ ID No. 10 (YGZFLRRZRPKLKWDNQ) wherein Z stands for any naturally occurring amino acid;
• h. SEQ ID No. 11 (YGZFLRRZFKVVT) wherein Z stands for any naturally occurring amino acid;
• and
• i. SEQ ID No. 12 (YGZFLRRZFKVVTRSQEDPNAYSGELFDA) wherein Z stands for any naturally occurring amino acid, and
• releasing dynorphins or dynorphin-variants on demand from said delivery vector.

A method of delivering a nucleic acid to a cell of the central nervous system, comprising:

• contacting the cell with the delivery vector or recombinant virus particle or liposome of under conditions sufficient for the DNA sequence encoding pre-prodynorphin or pre-prodynorphin-variant to be introduced into the cell,
• wherein the delivery vector drives expression of a pre-propeptide that is pre-prodynorphin or a pre-prodynorphin-variant wherein said pre-propeptide comprise the signal peptide and said signal peptide enables packing of a propeptide that is prodynorphin or a prodynorphin-variant, derived from said pre-propeptide, into vesicles,
• wherein the delivery vector comprises a DNA sequence comprising a sequence that encodes preprodynorphin or a preprodynorphin variant, wherein said sequence that encodes preprodynorphin or a preprodynorphin variant comprises a signal sequence that encodes a signal peptide, and
• wherein said pre-prodynorphin or pre-prodynorphin-variant comprises at least one of the following sequences:
• j. Dyn A that is SEQ ID No. 7 (AA 207-223 of SEQ ID No. 1;
• ppDyn) or a variant thereof consisting of the first 13 AA (first from the N-terminal end) or a variant thereof consisting of the first 8 AA (first from the N-terminal end);
• k. Dyn B that is SEQ ID No. 8 (AA 226-238 of SEQ ID No. 1;
• ppDyn);
• l. leumorphin that is SEQ ID No. 9 (AA 226-254 of SEQ ID No. 1;
• ppDyn);
• m. variants of Dyn A according to SEQ ID No. 7 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 7 (YGGFLRRI (SEQ ID NO:
• 18));
• n. variants of Dyn B according to SEQ ID No. 8 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 8 (YGGFLRRQ (SEQ ID NO:
• 19));
• o. variants of leumorphin according to SEQ ID No. 9 having an amino acid sequence identity of at least 60% within the first 8 AA counted from the N-terminus of SEQ ID No. 9 (YGGFLRRQ (SEQ ID NO:
• 19));
• p. SEQ ID No. 10 (YGZFLRRZRPKLKWDNQ) wherein Z stands for any naturally occurring amino acid;
• q. SEQ ID No. 11 (YGZFLRRZFKVVT) wherein Z stands for any naturally occurring amino acid;
• and
• SEQ ID No. 12 (YGZFLRRZFKVVTRSQEDPNAYSGELFDA) wherein Z stands for any naturally occurring amino acid.