Directed differentiation of oligodendrocyte precursor cells to a myelinating cell fate
The present invention provides methods of inducing differentiation of oligodendrocyte progenitor cells to a mature myelinating cell fate with a neurotransmitter receptor modulating agent. The present invention also provides methods of stimulating increased myelination in a subject in need thereof by administering said neurotransmitter receptor modulating agent. Methods of treating a subject having a demyelinating disease using a neurotransmitter receptor modulating agent are also provided.
1. A composition comprising:
a neurotransmitter receptor modulating agent, wherein the neurotransmitter receptor modulating agent is a muscarinic receptor antagonist and wherein the muscarinic receptor antagonist is benztropine, clemastine, or a salt thereof; and
an immunomodulatory agent useful for treating multiple sclerosis, wherein the immunomodulatory agent is a sphingosine 1-phosphate (S1P) agonist and wherein the S1P agonist is fingolimod (FTY720) or a salt thereof,
wherein the neurotransmitter receptor modulating agent and the immunomodulatory agent are formulated in a single pharmaceutical composition and wherein the immunomodulatory agent is formulated as a subtherapeutic dose.
2. The composition of claim 1 , wherein the muscarinic receptor antagonist is benztropine or a salt thereof.
3. The composition of claim 1 , wherein the composition is formulated for systemic administration.
4. The composition of claim 1 , wherein the composition is formulated for oral administration.
5. The composition of claim 1 , wherein the muscarinic receptor antagonist is clemastine or a salt thereof.
6. A kit comprising:
a neurotransmitter receptor modulating agent that is a muscarinic receptor antagonist, wherein the muscarinic receptor antagonist is benztropine, clemastine, or a salt thereof; and
an immunomodulatory agent useful for treating multiple sclerosis, wherein the immunomodulatory agent is a S1P agonist, and wherein the S1P agonist is fingolimod (FTY720) or a salt thereof;
wherein the immunomodulatory agent is formulated as a subtherapeutic dose.
7. The kit of claim 6 , wherein the neurotransmitter receptor modulating agent and the immunomodulatory agent are formulated in a single pharmaceutical composition.
8. The kit of claim 6 , wherein the muscarinic receptor antagonist is benztropine or a salt thereof.
9. The kit of claim 6 , wherein the muscarinic receptor antagonist is clemastine or a salt thereof.