Composition and method for treating neuronal ceroid lipofuscinosis
Provided herein are methods for treatment of a neurodegenerative disease, such as neuronal ceroid lipofuscinosis including administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent that mediates upregulation of TPP 1.
1. A method for treatment of a neurodegenerative disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent that mediates upregulation of TPP1, the agent comprising a lipid-lowering drug, wherein the neurodegenerative disease is neuronal ceroid lipofuscinosis, wherein the lipid lowering drug is a fibrate.
2. The method of claim 1 , wherein the fibrate is gemfibrozil or fenofibrate.
3. The method of claim 1 , wherein the neuronal ceroid lipofuscinosis is late infantile neuronal ceroid lipofuscinosis or Batten disease.
4. The method of claim 1 , wherein TPP1 is upregulated by increasing TPP1 mRNA levels, increasing TPP1 protein levels, increasing TPP1 enzymatic activity, or activating a PPAR-RXR heterodimer.
5. The method of claim 1 , wherein the composition further comprises a therapeutically effective amount of all-trans retinoic acid.
6. The method of claim 5 , wherein administering all-trans retinoic acid and a fibrate provides a greater therapeutic effect in the subject than administration of all-trans retinoic acid or the fibrate alone.
7. A method for treatment of a neurodegenerative disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent wherein the agent restores TPP1 activity, the agent comprising a lipid-lowering drug, wherein the neurodegenerative disease is neuronal ceroid lipofuscinosis, wherein the lipid lowering drug is a fibrate.
8. The method of claim 7 , wherein the fibrate is gemfibrozil or fenofibrate.
9. The method of claim 7 , wherein the therapeutically effective amount of the fibrate is lower when the fibrate is administered in combination with all-trans retinoic acid.
10. A method for treatment of neurodegenerative disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent that mediates upregulation of a gene selected from the group of Cln1, Clin2, Cln3, and any combination thereof, the agent comprising a lipid-lowering drug, and wherein the neurodegenerative disease is neuronal ceroid lipofuscinosis, wherein the lipid lowering drug is a fibrate.
11. The method of claim 10 , wherein the fibrate is gemfibrozil or fenofibrate.