Methods and pharmaceutical compositions for treating peripheral demyelinating diseases

Patent metadata

Field	Value
Publication number	US-12053480-B2
Application number	US-202016934142-A
Country	US
Kind code	B2
Filing date	Jul 21, 2020
Priority date	May 20, 2015
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present invention relates to methods and pharmaceutical compositions for treating peripheral demyelinating diseases. In particular the present invention relates to a method of treating a peripheral demyelinating disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of VDAC1 activity or expression.

First claim

The invention claimed is:

1. A method for screening a drug for the treatment of a peripheral demyelinating disease comprising the steps of i) providing a test compound, ii) determining whether the test compound is able to inhibit VDAC1 activity or expression and iii) positively selecting the test compound when it inhibits VDAC1 activity or expression.

2. The method of claim 1 wherein the peripheral demyelinating disease is selected from the group consisting of Refsum's disease, Abetalipoproteinemia, Tangier disease, Krabbe's disease, Metachromatic leukodystrophy, Fabry's disease, Dejerine-Sottas syndrome, Amyotrophic lateral sclerosis and Charcot-Marie-Tooth Diseases.

3. A method of treating an acquired peripheral demyelinating disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of VDAC1 activity or expression in Schwann cells, wherein said therapeutically effective amount is sufficient to inhibit VDAC1 expression in said Schwann cells, wherein said acquired peripheral demyelinating disease is selected from the group consisting of immune-mediated neuropathies, neuropathies associated with vasculitis or inflammation of the blood vessels in peripheral nerves, neuropathies associated with monoclonal gammopathies, neuropathies associated with tumors or neoplasms, neuropathies caused by infections, neuropathies caused by nutritional imbalance, and hypothyroid neuropathies.

4. The method of claim 3 wherein the inhibitor of VDAC1 expression is a siRNA.

5. A method of preventing, reducing or inhibiting Schwann cell demyelination in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of VDAC1 expression in Schwann cells.

6. The method of claim 5 wherein the subject suffers from a peripheral demyelinating disease.

7. The method of claim 6 wherein the peripheral demyelinating disease is hereditary.

8. The method of claim 7 wherein the hereditary peripheral demyelinating disease is selected from the group consisting of Refsum's disease, Abetalipoproteinemia, Tangier disease, Krabbe's disease, Metachromatic leukodystrophy, Fabry's disease, Dejerine Sottas syndrome, Amyotrophie lateral sclerosis and Charcot-Marie-Tooth Diseases.

9. The method of claim 6 wherein the peripheral demyelinating disease is acquired.

10. The method of claim 9 wherein acquired peripheral demyelinating disease is selected from the group consisting of diabetic neuropathies, immune-mediated neuropathies, neuropathies associated with vasculitis or inflammation of the blood vessels in peripheral nerves, neuropathies associated with monoclonal gammopathies, neuropathies associated with tumors or neoplasms, neuropathies caused by a chemotherapeutic agent, neuropathies caused by infections, neuropathies caused by nutritional imbalance, hypothyroid neuropathies, neuropathies caused by alcohol, peripheral demyelinating diseases caused by drugs or toxins and neuropathies caused by trauma or compression.

11. The method of claim 5 wherein the inhibitor of VDAC1 expression is a siRNA.

12. The method of claim 1 wherein the peripheral demyelinating disease is selected from the group consisting of diabetic neuropathies, immune-mediated neuropathies, neuropathies associated with vasculitis or inflammation of the blood vessels in peripheral nerves, neuropathies associated with monoclonal gammopathies, neuropathies associated with tumors or neoplasms, neuropathies caused by a chemotherapeutic agent, neuropathies caused by infections, neuropathies caused by nutritional imbalance, hypothyroid neuropathies, neuropathies caused by alcohol, peripheral demyelinating diseases caused by drugs or toxins and neuropathies caused by trauma or compression.

Assignees

• Inst Nat Sante Rech Med
• Univ Montpellier

Inventors

• Tricaud Nicolas
• Gonzalez Sergio

Classifications

• G01N33/5008

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title