USE OF ADENOSINE DEAMINASE FOR TREATING PULMONARY DISEASE
Provided are methods for treating an adenosine deaminase-mediated pulmonary disease such as asthma, pulmonary fibrosis, cystic fibrosis and chronic obstructive pulmonary disease in a mammal in need thereof, by administering and effective amount of a polymer-conjugated adenosine deaminase.
1 . A method of treating an adenosine deaminase-mediated pulmonary disease, comprising administering an effective amount of adenosine deaminase to a mammal in need thereof.
2 . The method of claim 1 , wherein the pulmonary disease is mediated with an elevated level of adenosine.
3 . The method of claim 1 , wherein the pulmonary disease is selected from the group consisting of asthma, pulmonary fibrosis, cystic fibrosis and chronic obstructive pulmonary disease.
4 . The method of claim 1 , wherein the pulmonary disease is a chemotherapy-mediated pulmonary disease.
5 . The method of claim 1 wherein the adenosine deaminase is administered by inhalation or parenterally.
6 . The method of claim 1 , wherein the adenosine deaminase is administered prophylactically, concurrently or subsequently with a chemotherapeutic agent.
7 . The method of claim 1 , wherein the adenosine deaminase is conjugated to a polyalkylene oxide.
8 . The method of claim 7 , wherein the polyalkylene oxide-conjugated adenosine deaminase is administered as an aerosol or as a dry powder.
9 . The method of claim 1 wherein the adenosine deaminase is obtained from a bovine source.
10 . The method of claim 1 wherein the adenosine deaminase is obtained from a human source.
11 . The method of claim 1 , wherein the adenosine deaminase is a recombinant adenosine deaminase.
12 . The method of claim 7 , wherein the polyalkylene oxide ranges in size from about 5,000 Daltons to about 45,000 daltons.
13 . The method of claim 7 , wherein the polyalkylene oxide comprises a straight, branched or multi-arm chain.
14 . The method of claim 7 , wherein the polyalkylene oxide is polyethylene glycol.
15 . The method of claim 14 , wherein the adenosine deaminase conjugated to polyethylene glycol is pegademase bovine.
16 . The method of claim 1 , wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to maintain plasma ADA activity in the range of from about 15 to about 35 μmol/hr/mL.
17 . The method of claim 1 , wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to reduce lung adenosine levels to less than about 10 nmoles per mg protein.
18 . The method of claim 17 , wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to reduce lung adenosine levels to less than about 5 nmoles per mg protein.
19 . The method of claim 1 , further comprising administering an effective dose of a second pharmacologically active agent in combination with the adenosine deaminase.
20 . The method of claim 19 , wherein the second pharmacologically active agent is theophylline or a bronchodilator.
21 . The method of claim 19 , wherein the bronchodilator is beta-adrenergic bronchodilator.
22 . The method of claim 21 , wherein the beta-adrenergic bronchodilator is selected from the group consisting of salmeterol, albuterol or terbutaline.
23 . A kit for treating pulmonary disease in mammals, comprising adenosine deaminase and instructions for use in the treatment of pulmonary disease.
24 . An inhalable formulation, comprising adenosine deaminase and a bronchodilator.
25 . An inhaler suitable for use in the treatment of pulmonary conditions, comprising the inhalable formulation of claim 24 and a propellant.