Methods of lysosomal storage disease therapy
Methods of treating a lysosomal storage disorder and methods of increasing cellular uptake of a lysosomal enzyme using β2 agonists or therapeutic agents that increase expression of receptors for a lysosomal enzyme.
1. A method of treating a patient having a lysosomal storage disease characterized by reduced or deficient activity of a lysosomal enzyme comprising administering a β2 agonist to the patient to thereby increase expression of receptors for the lysosomal enzyme and to decrease lysosomal enzyme metabolite accumulation of the lysosomal storage disease in the patient.
2. The method of claim 1 , wherein the β2 agonist is administered prior to or subsequent to a lysosomal enzyme replacement therapy.
3. The method of claim 1 , wherein the patient is a human patient.
4. The method of claim 1 , wherein the lysosomal storage disease is Pompe disease, adult-onset glycogen storage disease II (GSD II), Gaucher disease, Fabry disease, mucopolysaccharidosis type I, mucopolysaccharidosis type II, or Niemann-Pick disease.
5. The method of claim 1 , wherein the lysosomal storage disease is characterized by reduced or deficient activity of the lysosomal enzyme in the brain of the patient.
6. The method of claim 1 , wherein the lysosomal enzyme is acid α-glucosidase.
7. The method of claim 1 , wherein the receptors are Cation Independent Mannose-6-Phosphate Receptors (CI-MPR).
8. The method of claim 1 , wherein the β2 agonist is clenbuterol, formoterol, salmeterol, albuterol, or a combination thereof.
9. The method of claim 1 , wherein the administering is performed orally, intranasally, intravenously, intramuscularly, or transdermally.
10. The method of claim 1 , wherein expression of receptors for the lysosomal enzyme is increased in the brain of the patient.
11. The method of claim 1 , wherein the β2 agonist is administered prior to or subsequent to a gene therapy, wherein the gene therapy comprises expression of a vector encoding a lysosomal enzyme in the patient.
12. The method of claim 11 , wherein the vector is a viral vector.
13. The method of claim 12 , wherein the viral vector is an adeno-associated virus (AAV) vector.
14. The method of claim 2 , wherein the patient receives the lysosomal enzyme replacement therapy prior to increasing expression of receptors for the lysosomal enzyme in the patient.
15. The method of claim 2 , wherein the patient receives the lysosomal enzyme replacement therapy subsequent to increasing expression of receptors for the lysosomal enzyme in the patient.
16. The method of claim 1 , further comprising administering a lysosomal enzyme replacement therapy to the patient concurrently with the β2 agonist.
17. The method of claim 2 , whereby efficacy of the enzyme replacement therapy in brain is enhanced.