Compositions and methods for improving mitochondrial function

Patent metadata

Field	Value
Publication number	US-12285446-B2
Application number	US-202318351198-A
Country	US
Kind code	B2
Filing date	Jul 12, 2023
Priority date	Jan 23, 2018
Publication date	Apr 29, 2025
Grant date	Apr 29, 2025

Abstract

Provided herein are methods and compositions comprising a bacterium or a metabolite thereof for enhancing mitochondrial and/or peroxisomal function.

First claim

The invention claimed is:

1. A method of treating Friedrich's Ataxia, the method comprising:
administering to a subject at risk of or suffering from Friedrich's Ataxia, a therapeutically effective amount of a composition, thereby reducing the severity of at least one symptom of Friedrich's Ataxia compared to a subject without the administration, and
wherein the composition comprises:
a measured amount of a bacterial species that comprises and expresses nucleic acid sequences encoding membrane-bound PQQ-dependent glucose dehydrogenase (mGDH), ubiquinol-cytochrome c reductase iron-sulfur subunit, TonB-dependent receptor, carbon-nitrogen hydrolase, and ubiquinol oxidase subunit II, or an extract or fraction derived therefrom,
wherein the extract or fraction of the bacterial species comprises membrane-bound PQQ-dependent glucose dehydrogenase (mGDH), ubiquinol-cytochrome c reductase iron-sulfur subunit, TonB-dependent receptor, carbon-nitrogen hydrolase, and ubiquinol oxidase subunit II expressed from the nucleic acid sequences,
wherein the bacterial species is from the Acetobacteriaceae family.

2. The method of claim 1 , wherein the bacterium is Gluconobacter spp, Acetobacter spp., Gluconoacaetobacter spp., Acidomonas spp, Ameyamaea spp., Asaia spp., Granulibacter spp., Kozakia spp., Neoasaia spp., Neokomagataea spp., Saccharibacter spp., Swaminathania spp., or Tanticharoenia spp.

3. The method of claim 1 , wherein one or more of the nucleic acid sequences are exogenous nucleic acid sequences.

4. The method of claim 1 , wherein the composition further comprises one or more added bacterial metabolites selected from the group consisting of gluconic acid, 2-keto-gluconic acid, 5-keto-gluconic acid, and 2,5-diketo-D-gluconic acid.

5. The method of claim 1 , wherein the bacterial species expresses and/or produces one or more added bacterial metabolites selected from the group consisting of gluconic acid, 2-keto-gluconic acid, 5-keto-gluconic acid, and 2,5-diketo-D-gluconic acid.

6. The method of claim 1 , wherein the composition is formulated as a food, a beverage, a feed composition, a probiotic, a nutritional supplement, or a pharmaceutical composition.

7. The method of claim 1 , wherein the composition further comprises a prebiotic.

8. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.

9. The method of claim 1 , wherein the step of administering comprises orally administering the composition.

10. The method of claim 8 , wherein the composition is formulated for oral administration.

11. The method of claim 9 , wherein the composition is an enteric-coated formulation.

12. The method of claim 1 , wherein the subject is human.

13. The method of claim 1 , wherein the administering increases one or more of expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), mitochondrial transcription factor A (TFAM), AMP-activated protein kinase (AMPK) phosphorylation level, nuclear respiratory factor-2 (Nrf2) protein level, PGC-la mRNA level, TFAM mRNA level, mitochondrial DNA replication, mitochondrial DNA copy number (mtDNA), and expression of at least one mitochondrial β-oxidation enzyme, compared to a subject without the administration.

14. The method of claim 1 , wherein the at least one symptom is selected from the group consisting of impaired speech, visual/hearing problems, cardiovascular disease, diabetes, cognitive decline, confusion, delusion, disorientation, forgetfulness, difficulty concentrating, inability to generate new memories, inability to do simple math, inability to recognize common items, aggression, agitation, irritability, meaningless repetition of own words, personality changes, restlessness, lack of restraint, wandering, anger, apathy, general discontent, loneliness, mood swings, depression, hallucination, paranoia, loss of appetite, inability to combine muscle movements, and jumbled speech.

Assignees

• Massachusetts Gen Hospital

Inventors

• Ruvkun Gary
• Govindan J Amaranath
• Jayamani Elamparithi

Classifications

• A61K9/0056

  Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C12N2500/16

  Magnesium; Mg chelators · CPC title

• C12N2500/34

  Sugars · CPC title

• C12N2500/14

  Calcium; Ca chelators; Calcitonin · CPC title