L-DOPA microbiome therapy

Patent metadata

Field	Value
Publication number	US-12539287-B2
Application number	US-202318153739-A
Country	US
Kind code	B2
Filing date	Jan 12, 2023
Priority date	Feb 27, 2018
Publication date	Feb 3, 2026
Grant date	Feb 3, 2026

Abstract

The present invention generally provides methods and compositions for the treatment of Parkinson's disease and depression and/or anxiety. The invention relates to recombinant microorganisms, particularly gut-colonizing probiotics, modified to produce L-DOPA.

First claim

What is claimed is:

1 . A pharmaceutical composition comprising:
a recombinant E. coli Nissle 1917 (EcN) cell comprising a hpaB and hpaC nucleotide sequence as set forth in SEQ ID NO: 1 and 2 or an hpaBC nucleotide as set forth in SEQ ID NO: 3, wherein the recombinant EcN cell is capable of producing L-DOPA and colonizing the gut of a subject, thereby providing L-DOPA in a sustained manner, wherein L-DOPA produced by the recombinant EcN cell in the gut of the subject crosses the blood-brain barrier and increases dopamine levels in the brain to alleviate neurological symptoms of Parkinson's disease or symptoms of depression and/or anxiety; and a carrier.

2 . The pharmaceutical composition of claim 1 , wherein said composition comprises from about 10 6 CFU to about 10 12 CFU of said recombinant EcN cell.

3 . The pharmaceutical composition of claim 2 , wherein said composition comprises about 10 9 CFU of said recombinant EcN cell.

4 . The pharmaceutical composition of claim 1 , wherein said composition further comprises L-Tyrosine.

5 . The pharmaceutical composition of claim 1 , wherein said recombinant EcN cell comprises an hpaBC nucleotide as set forth in SEQ ID NO: 3.

6 . The pharmaceutical composition of claim 5 , wherein said hpaB and hpaC nucleotide sequence or said hpaBC nucleotide sequence is operably linked to promoter sequence comprising one or more of SEQ ID NOs: 4-6.

7 . A recombinant E. coli Nissle 1917 (EcN) cell comprising a hpaB and hpaC nucleotide sequence as set forth in SEQ ID NO: 1 and 2 or an hpaBC nucleotide as set forth in SEQ ID NO: 3, wherein the recombinant EcN cell is capable of producing L-DOPA and colonizing the gut of a subject, thereby providing L-DOPA in a sustained manner, wherein L-DOPA produced by the recombinant EcN cell in the gut of the subject crosses the blood-brain barrier and increases dopamine levels in the brain to alleviate neurological symptoms of Parkinson's disease or symptoms of depression and/or anxiety.

8 . The recombinant EcN cell of claim 7 , wherein said recombinant EcN cell comprises an hpaBC nucleotide as set forth in SEQ ID NO: 3.

9 . The recombinant EcN cell of claim 8 , wherein said hpaB and hpaC nucleotide sequence or said hpaBC nucleotide sequence is operably linked to promoter sequence comprising one or more of SEQ ID NOs: 4-6.

Assignees

• Univ Iowa State Res Found Inc
• Univ Texas

Inventors

• Kanthasamy Anumantha G
• Abdalla Ahmed
• Phillips Gregory
• Backes Nicholas
• Ellington Andrew D
• THYER Ross

Classifications

• A61K2035/115

  Probiotics · CPC title

• C12N9/0073

  with NADH or NADPH as one donor, and incorporation of one atom of oxygen 1.14.13 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title