Targeting NAD+ to treat chemotherapy and radiotherapy induced cognitive impairment, neuropathies and inactivity

Patent metadata

Field	Value
Publication number	US-10603334-B2
Application number	US-201615570210-A
Country	US
Kind code	B2
Filing date	Apr 28, 2016
Priority date	Apr 28, 2015
Publication date	Mar 31, 2020
Grant date	Mar 31, 2020

Abstract

Methods and compositions for preventing or treating peripheral neuropathy, cognitive deficits, inactivity, depression, chemotherapy and/or radiotherapy induced peripheral neuropathy and cognitive deficits, and improving cognitive performance, in a subject in need thereof are disclosed. The disclosed methods include the step of administering to the subject an effective amount of an agent that increases the level of NAD + in the subject.

First claim

The invention claimed is:

1. A method for prophylactically treating chemotherapy induced cognitive impairments (CICI) in a subject, comprising administering to a subject who has undergone exposure to a chemotherapy agent, is undergoing exposure to a chemotherapy agent, or will undergo exposure to a chemotherapy agent, an effective amount of an agent that increases the level of NAD + in the subject, whereby chemotherapy agent-induced cognitive impairments (CICI) are prophylactically treated,
wherein the agent that increases the level of NAD + is an NAD + precursor selected from nicotinamide mononucleotide (NMN), nicotinic acid, nicotinamide, nicotinamide riboside (NR), nicotinic acid mononucleotide, nicotinic acid riboside, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), adenosine, adenine, and adenosine monophosphate.

2. The method of claim 1 , wherein the chemotherapy agent induced neurotoxic damage prophylactically treated comprises chemotherapy induced peripheral neuropathies (CIPN).

3. The method of claim 1 , wherein the chemotherapy agent induced neurotoxic damage prophylactically treated comprises chemotherapy induced inactivity.

4. The method of claim 1 , wherein the chemotherapy agent induced neurotoxic damage prophylactically treated comprises chemotherapy induced depression, anxiety, melancholy, post-traumatic stress disorder, impaired sleep, circadian rhythm disorders, or other mental health/psychological disorder.

5. The method of claim 1 , wherein the agent that increases the level of NAD+ in the subject is administered at the same time as the subject undergoes exposure to the chemotherapy agent.

6. The method of claim 1 , wherein the neurotoxic damage prophylactically treated comprises pain and/or peripheral neuropathy.

7. The method of claim 1 , wherein the neurotoxic damage prophylactically treated comprises inactivity, lethargy, or malaise.

8. The method of claim 1 , wherein the neurotoxic damage prophylactically treated comprises depression, anxiety, melancholy, post-traumatic stress disorder or other mental health/psychological disorder.

9. The method of claim 1 , wherein the chemotherapy agent is selected from cisplatin, carboplatin, oxaliplatin, cyclophosphamide, altretamine, plicamydin, chlorambucil, chlormethine, ifosfamide, melphalan, carmustine, fotemustine, lomustine, streptozocin, busulfan, dacarbazine, mechlorethamine, procarbazine, temozolomide, thioTEPA, uramustine, paclitaxel, docetaxel, vinblastine, vincristine, vindesine, vinorelbine, hexamethylmelamine, etoposide, teniposide, methotrexate, pemetrexed, raltitrexed, cladribine, clofarabine, fludarabine, mercaptopurine, tioguanine, capecitabine, cytarabine, fluorouracil, fluxuridine, gemcitabine, daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, valrubicin, bleomycin, hydroxyurea, mitomycin, topotecan, irinotecan, aminolevulinic acid, methyl aminolevulinate, porfimer sodium, verteporfin, alitretinoin, altretamine, amsacrine, anagrelide, arsenic trioxide, asparaginase, bexarotene, bortezomib, celecoxib, denileukin, diftitox, erlotinib, estramustine, gefitinib, hydroxycarbamide, imatinib, pentostatin, masoprocol, mitotane, pegaspargase, and tretinoin, or combinations thereof.

10. The method of claim 1 , wherein the agent that increases the level of NAD + is an activator to an enzyme involved in NAD + biosynthesis.

11. The method of claim 1 , wherein the agent that increases the level of NAD + is administered at a dose of between 0.5-5 grams per day.

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

13. The method of claim 1 , comprising administering the agent that increases the level of NAD+ in the subject before the subject undergoes exposure to the chemotherapy agent.

14. The method of claim 1 , comprising administering the agent that increases the level of NAD+ in the subject after the subject undergoes exposure to the chemotherapy agent.

Assignees

• Newsouth Innovations Pty Ltd
• Newsouth Innovation Pty Ltd

Inventors

• Wu Lindsay Edward
• Sinclair David A

Classifications

• A61K38/45

  Transferases (2) · CPC title

• A61K31/706 Primary

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• C12Y204/02012

  Nicotinamide phosphoribosyltransferase (2.4.2.12), i.e. visfatin · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title