Methods and uses of slit for treating fibrosis

Patent metadata

Field	Value
Publication number	US-2016120940-A1
Application number	US-201414896168-A
Country	US
Kind code	A1
Filing date	Jun 4, 2014
Priority date	Jun 4, 2013
Publication date	May 5, 2016
Grant date	—

Abstract

The present disclosure provides methods and uses of Slit protein and nucleic acid for inhibiting fibrosis and fibrotic-related disorders, for example, of the kidney, lung, heart, liver, or a wound. The Slit protein can be, for example, Slit2 or Slit2-N, or a Slit variant that can bind the Robo receptor and induce signalling. Also provided are pharmaceutical compositions comprising the Slit protein or nucleic acid and an additional anti-fibrotic agent.

First claim

1 . A method of inhibiting fibrosis comprising administering a Slit protein or nucleic acid to a cell or animal in need thereof.

2 . The method of claim 1 , wherein the fibrosis is due to increased collagen deposition and/or synthesis.

3 . The method of claim 1 , wherein the fibrosis is kidney fibrosis, lung fibrosis, cardiac fibrosis, liver fibrosis or fibrosis deposited due to a wound.

4 . A method of treating a fibrotic-related disorder, condition or disease or a risk of a fibrosis comprising administering a Slit protein or nucleic acid to a cell or animal in need thereof.

5 . The method of claim 4 , wherein the fibrotic-related disorder, condition or disease is glomerulonephritis, diabetic nephropathy, lupus nephritis, toxic nephropathy, chronic pyelonephritis, polycystic kidney disease, renal scarring, wound scarring, post-cardiac infarction, cystic fibrosis, idiopathic pulmonary fibrosis, cirrhosis, chronic obstructive pulmonary disease, cardiomyopathy, and all other progressive diseases marked by fibrosis.

6 . The method of claim 4 , wherein the fibrotic-related disorder, condition or disease is chronic kidney disease.

7 . The method of claim 6 , wherein the Slit2 protein or nucleic acid is used 5 days after acute kidney injury, or later.

8 . The method of claim 7 , wherein the Slit2 protein or nucleic acid is used 10 days after acute kidney injury, or later.

9 . The method of claim 6 , wherein the subject with chronic kidney disease has a glomerular filtration rate of less than 60 ml/min/1.73 m 2 .

10 . The method of claim 6 , wherein the subject with chronic kidney disease is at stage 3 or greater.

11 . The method of claim 4 , wherein the fibrotic disorder, condition or disease is diabetic nephropathy.

12 . (canceled)

13 . The method of claim 1 , wherein the Slit protein or nucleic acid is suitable for daily, weekly or monthly use.

14 . (canceled)

15 . (canceled)

16 . The method of claim 1 , wherein the Slit protein or nucleic acid is suitable for local administration.

17 . The method of claim 1 , wherein the Slit protein or nucleic acid is suitable for long-term use.

18 . The method of claim 1 , wherein the Slit protein is Slit1, 2 or 3, or a variant thereof that binds the Robo receptor and induces signaling.

19 . The method of claim 18 , wherein the Slit protein is Slit2 or Slit2-N.

20 . A pharmaceutical composition comprising a Slit protein or nucleic acid and an additional anti-fibrotic agent.

21 . The pharmaceutical composition of claim 20 , wherein the Slit protein is Slit1, 2 or 3, or a variant thereof that binds the Robo receptor and induces signaling.

22 . The pharmaceutical composition of claim 21 , wherein the Slit protein is Slit2 or Slit2-N.

Assignees

• Hospital For Sick Children

Inventors

• Robinson Lisa Annette
• Yuen Darren Arthur Vee-Yip

Classifications

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61K38/1709 Primary

  from mammals · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title