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Bdnf Mimetic Peptide Amphiphiles
| Content Provider | The Lens |
|---|---|
| Description | L'invention concerne des amphiphiles peptidiques (PA) et des nanostructures de PA supramoléculaires qui imitent le facteur neurotrophique dérivé du cerveau (BDNF), un facteur de croissance qui induit une survie neuronale, une maturation et une activité électrique accrue. En particulier, l'invention concerne des biomatériaux injectables comprenant des PA mimétiques du BDNF, ainsi que des méthodes d'utilisation des PA mimétiques du BDNF pour le traitement ou la prévention de lésions, de maladies et de troubles neurologiques. |
| Abstract | Provided herein are peptide amphiphiles (PAs) and supramolecular PA nanostructures that mimic brain derived neurotrophic factor (BDNF), a growth factor that induces neuronal survival, maturation, and increased electrical activity. In particular, injectable biomaterials comprising BDNF mimetic PAs are provided, as well as methods of using BDNF mimetic PAs for the treatment or prevention of neurological injuries, diseases, and disorders. |
| Related Links | https://www.lens.org/lens/patent/010-218-250-916-48X/frontpage |
| Language | English |
| Publisher Date | 2019-10-10 |
| Access Restriction | Open |
| Alternative Title | Amphiphiles Peptidiques Mimétiques Du Bdnf |
| Content Type | Text |
| Resource Type | Patent |
| Date Applied | 2019-04-05 |
| Agent | Staple, David W. |
| Applicant | Univ Northwestern |
| Application No. | 2019026077 |
| Claim | CLAIMS A composition comprising brain derived neurotrophic factor (BDNF) peptide amphiphiles. The composition of claim 1, wherein the peptide amphiphiles comprise a hydrophobic non-peptide tail, a structured peptide segment, a charged peptide segment, and a BDNF peptide. The composition of claim 2, wherein the hydrophobic non-peptide tail comprises an 8-24 carbon alkyl chain (C 8-24 ). 4 The composition of claim 2, wherein the structured peptide segment comprises VVAA (SEQ ID NO: 2) or any suitable combination or V and/or A residues. The composition of claim 2, wherein the structured peptide segment has propensity to form b-sheet-like structures with adjacent structured peptide segments. The composition of claim 2, wherein the charged peptide segment comprises an acidic, basic, or zwitterionic peptide segment. The composition of claim 2, wherein the charged peptide segment comprises EE or KK. The composition of claim 7, wherein the charged peptide segment comprises EEEE (SEQ ID NO: 10). The composition of claim 2, wherein the peptide amphiphile comprises EEEEAAVV- C 8-24 (SEQ ID NO: 3). The composition of claim 2, wherein the BDNF peptide comprises at least 70% sequence similarity with one of SEQ ID NO: 1. The composition of claim 10, wherein the BDNF peptide comprises at least 70% sequence identity with one of SEQ ID NO: 1. The composition of claim 11, wherein the BDNF peptide comprises SEQ ID NO: 1. The composition of claim 2, wherein the BDNF peptide is a cyclic peptide. The composition of claim 13, wherein the BDNF peptide comprises SEQ ID NO: 1 and is cyclized using the d-Proline[dP]. The composition of claim 2, wherein the BDNF peptide is attached to the charged peptide by a linker. The composition of claim 15, wherein the linker comprises a PEG linker. The composition of claim 16, wherein the linker comprises a PEG6 linker. The composition of claim 15, wherein the linker is attached to the BDNF peptide at lysine(aK). The composition of claim 2, wherein the peptide amphiphile comprises RKK(aK)(dP)-(PEG6 Spacer)-EEEEAAVV-C 8 -24 (SEQ ID NO: 4). The composition of claim 19, wherein the peptide amphiphile comprises RKK(aK)(dP)-(PEG6 Spacer)-EEEEAAVV-Ci 6 (SEQ ID NO: 5). A nanofiber comprising the self-assembled peptide amphiphiles of one of claims 1-20. The nanofiber of claim 21, further comprising filler peptide amphiphiles, wherein the filler peptide amphiphiles do not comprise a bioactive moiety. The nanofiber of claim 22, wherein the filler peptide amphiphiles comprise a hydrophobic non-peptide tail, a structured peptide segment, and a charged peptide segment. The nanofiber of claim 23, wherein the hydrophobic non-peptide tail of the filler peptide comprises an 8-24 carbon alkyl chain (Ce-24). The nanofiber of claim 21, wherein the structured peptide segment of the filler peptide comprises VVAA (SEQ ID NO: 2) or any suitable combination or V and/or A residues. The nanofiber of claim 25, wherein the structured peptide segment of the filler peptide has propensity to form b-sheet-like structures with adjacent structured peptide segments. The nanofiber of claim 21, wherein the charged peptide segment of the filler peptide comprises an acidic, basic, or zwitterionic peptide segment. The nanofiber of claim 27, wherein the charged peptide segment comprises EE or KK. The nanofiber of claim 18, wherein the filler peptide amphiphile comprises EEAAVV-C8-24 (SEQ ID NO: 6). A method comprising administering a nanofiber of one of claims 21-29 to a subject. The method of claim 30, wherein the nanofiber is pharmaceutically formulated. The method of claim 31, wherein the nanofiber is administered by injection. The method of claim 30, wherein the nanofiber is administered to enhance neuronal survival, growth, and/or synaptic plasticity. The method of claim 30, wherein the nanofiber is administered to treat and/or prevent a neurological and/or psychiatric disease or condition. The method of claim 30, wherein administering the nanofiber activates TrkB signaling. The method of claim 35, wherein administering the nanofiber activates MAPK, PI3K and/or PLCy. The method of claim 30, wherein administering the nanofiber guides endogenous neural cells to repopulate dysfunctional areas of the central nervous system. A kit comprising the nanofiber of one of claims 21-29, and one or more additional components for delivering the nanofiber, storing the nanofiber, and/or for the treatment/prevention of a neurological and/or psychiatric disease or condition. |
| CPC Classification | Preparations For Medical; Dental Or Toiletry Purposes PEPTIDES |
| Extended Family | 004-316-907-627-618 010-218-250-916-48X 163-993-240-594-216 |
| Patent ID | 2019195741 |
| Inventor/Author | Stupp Samuel I Kolberg Alexandra N Alvarez Zaida |
| IPC | A61K9/70 C07K14/475 |
| Status | Pending |
| Simple Family | 004-316-907-627-618 010-218-250-916-48X 163-993-240-594-216 |
| CPC (with Group) | A61K9/70 C07K14/475 A61K9/0019 C07K7/64 |
| Issuing Authority | United States Patent and Trademark Office (USPTO) |
| Kind | Patent Application Publication |
