USE OF NRF2 INDUCERS TO TREAT EPIDERMOLYSIS BULLOSA SIMPLEX AND RELATED DISEASES

• US 20110003747A1
• Filed: 07/17/2008
• Published: 01/06/2011
• Est. Priority Date: 07/20/2007
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Coloumbe, Pierre A., Kerns, Michelle L.
• Application Number:
  US12/690,494
• Publication Number:
  US 20110003747A1
• Time in Patent Office: Days
• US Class Current: 514/9.2
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61K 31/275 Nitriles; Isonitriles
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders

Abstract

The present invention relates to methods and compositions for the prevention and treatment of keratin-based skin diseases. In particular, the application describes compositions and methods of treating a patient suffering from skin blistering comprising the use of phase II enzyme inducers.

Claims

1. A method to ameliorate the mechanical resilience of skin in a patient in need thereof comprising administering to the patient a composition comprising a therapeutically effective amount of an Nrf2 inducer.

2. The method of claim 1, wherein the patient suffers from skin blistering.

3. The method of claim 1, wherein the Nrf2 inducer is a phase II enzyme inducer.

4. The method of claim 3, wherein the phase II inducer is an isothiocyanate.

5. The method of claim 4, wherein the phase IT enzyme inducer is sulforaphane.

6. The method of claim 4, wherein the phase II enzyme inducer is a sulforaphane synthetic analogue.

8. The method of claim 1, wherein the Nrf2 inducer is keratinocyte growth factor.

12. The method of claim 1, wherein the composition comprising the Nrf2 inducer is topically administered to the patient.

16. The method of claim 1, wherein the patient is a mammal.

17. The method of claim 16, wherein the mammal is a human.

7. (canceled)

9-11. -11. (canceled)

13-15. -15. (canceled)

18. A method for treating or preventing skin blistering in a patient comprising administering to the patient a composition comprising a therapeutically effective amount of an Nrf2 inducer.

19. The method of claim 18, wherein the patient suffers from Epidermolysis bullosa simplex.

20. The method of claim 18, wherein the patient suffers from Epidermolysis bullosa simplex-Weber-Cockayne type, Epidermolysis bullosa simplex-Koebner type, Epidermolysis bullosa simplex with mottled pigmentation, Epidermolysis bullosa simplex-Dowling-Meara type, or Epidermolysis bullosa simplex with muscular dystrophy.

21. The method of claim 20, wherein the Epidermolysis bullosa simplex is caused by a mutation at the K14 locus.

22. The method of claim 18, wherein the Nrf2 inducer is a phase II enzyme inducer.

23-36. -36. (canceled)

37. A method for treating or preventing a keratin-based skin disease in a patient comprising administering to the patient a composition comprising a therapeutically effective amount of an Nrf2 inducer.

38. The method of claim 37, wherein the keratin-based skin disease is selected from the group consisting of epidermolytic hyperkeratosis, ichtyosis bullosa of Siemens, pachyonychia congenita, epidermolytic or non-epidermolytic palmoplantar keratoderma (diffuse or focal) steatocystoma multiplex, Nacgeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis.

39-54. -54. (canceled)

55. A composition for topical application to the skin comprising a therapeutically effective amount of an Nrf2 inducer and a carrier that allows the Nrf2 inducer to reach basal keratinocytes in the epidermis.

57. The composition of claim 55, wherein the Nrf2 inducer is a phase II enzyme inducer.

56. (canceled)

58-67. -67. (canceled)