Ameliorating Nervous Systems Disorders
The present disclosure provides methods for the treatment of a mammal having a neurological condition, disease, or injury. The methods involve increasing the number of functional GABAergic interneurons at or near the site of the neurological disease, injury, or condition.
1 . A method for the treatment of a mammal having a neurological condition, disease, or injury comprising:
increasing the number of functional GABAergic interneurons at or near the site of the neurological disease, injury, or condition, wherein said functional GABAergic interneurons functionally integrate with endogenous neurons and restore balance to neuronal circuitry that is dysregulated in neurological conditions, diseases, or injuries.
2 . The method of claim 1 , wherein the increase in said functional GABAergic interneurons is by transplantation comprising the injection of MGE (medial ganglionic eminence) precursor cells.
3 . The method of claim 2 , wherein the MGE precursor cells are able to migrate at least 0.5 mm from the transplantation site.
4 . The method of claim 1 , wherein the neurological condition, disease, or injury is a degenerative disease, genetic disease, acute injury, or chronic injury.
5 . The method of claim 4 , wherein the neurological condition, disease, or injury comprises Parkinson's disease, epilepsy, spasticity, multiple sclerosis, stroke, spinal cord injury, brain injury, or chronic pain disorders.
6 . The method of claim 3 , wherein the MGE precursor cells express a therapeutic protein or peptide, or neurotransmitter.
7 . The method of claim 6 , wherein the therapeutic protein or peptide comprises a neurotrophin, a neuropoietic cytokine, a fibroblast growth factors (e.g., acidic and basic FGF), an inhibitory growth factor, or a cytokine useful in the treatment of infectious disease, brain tumors, or brain metastases.
8 . The method of claim 4 , wherein the neurological condition is epilepsy, wherein transplantation of MGE precursor cells result in at least a 10% reduction in spontaneous electrographic seizure activity.
9 . The method of claim 4 , wherein the neurological condition is epilepsy, wherein transplantation of MGE precursor cells result in at least a 10% reduction in seizure duration.
10 . The method of claim 4 , wherein the neurological condition is epilepsy, wherein transplantation of MGE precursor cells result in at least a 10% reduction in seizure frequency.
11 . The method of claim 4 , wherein the neurological condition is epilepsy, wherein transplantation of MGE precursor cells result in at least a 10% reduction in required antiepileptic drug use.
12 . The method of claim 4 , wherein the neurological disease is Parkinson's disease, wherein transplantation of MGE precursor cells result in at least a 10% reduction in required antiParkinsonian drug use.
13 . The method of claim 4 , wherein the neurological disease is Parkinson's disease, wherein transplantation of MGE precursor cells result in at least a 10% reduction in tremor at rest, rigidity, akinesia, bradykinesia, postural instability, flexed posture and/or freezing.
14 . The method of claim 4 , wherein the neurological disease is Parkinson's disease, wherein the MGE cells transplanted into the striatum survive for at least 6 months.
15 . The method of claim 4 , wherein the neurological condition is spasticity, wherein transplantation of MGE precursor cells obviates the need for intrathecal medication or surgery.
16 . The method of claim 4 , wherein the neurological condition is spasticity, wherein transplantation of MGE precursor cells result in at least a 10% reduction in required antispasmodic drug use.
17 . The method of claim 2 , wherein the MGE precursor cells are injected into the striatum, basal ganglia, dorsal ganglia, ventral horn, or lumbar theca.
18 . The method as in claim 2 , wherein the mammal does not require immunosuppressive therapy following transplantation.