Compositions and methods for treating neurological disorders
The present disclosure provides methods for treating neurological disorders, generally involving modulating protein kinase D1 (PKD1) activity levels in a neuron or glial cell in an individual in need thereof. The present disclosure provides antibodies specific for PKD1. The present disclosure provides a genetically modified non-human mammal deficient in PKD1 activity.
1. A method for treating a neurodegenerative disease in an individual, the method comprising administering to the individual an effective amount of an inhibitory nucleic acid that reduces the level of active protein kinase D1 (PKD1) in a neuronal cell and/or a glial cell in the individual, wherein the neurodegenerative disease is Huntington's disease or Alzheimer's disease.
2. The method of claim 1 , wherein the inhibitory nucleic acid comprises an antisense region that is complementary to a nucleotide sequence in a target PKD1-encoding nucleic acid.
3. The method of claim 2 , wherein the agent is an inhibitory nucleic acid comprises an antisense region that is complementary to a PKD1 target sequence from SEQ ID NOs: 17-21.
4. The method of claim 1 , wherein the inhibitory nucleic acid comprises one or more chemical modifications that increase stability.
5. The method of claim 1 , wherein the inhibitory nucleic acid is formulated with a lipid.