SOBETIROME IN THE TREATMENT OF MYELINATION DISEASES
Methods of treating a subject having or at risk of developing a neurodegenerative disease or condition associated with demyelination, insufficient myelination, or underdevelopment of myelin sheath are described. The methods include administration of a therapeutically effective amount of sobetirome, or a pharmaceutically acceptable salt thereof.
1 . A method of treating a subject having or at risk of developing a disease or condition associated with demyelination, insufficient myelination, or underdevelopment of myelin sheath, comprising administering to the subject a therapeutically effective amount of sobetirome or a pharmaceutically acceptable salt thereof.
2 . A method of inhibiting demyelination of a neuron, or promoting myelination of a neuron, in a patient in need thereof, comprising contacting the neuron with sobetirome, or a pharmaceutically acceptable salt thereof, wherein the patient has or is at risk of developing a disease or condition associated with demyelination, insufficient myelination, or underdevelopment of myelin sheath.
3 . The method of claim 1 , wherein the disease or condition is multiple sclerosis, a leukodystrophy, a leukoencephalopathy, an idiopathic inflammatory demyelinating disease, or Alzheimer's disease.
4 . The method of claim 3 , wherein the multiple sclerosis is relapsing-remitting multiple sclerosis, primary-progressive multiple sclerosis, secondary-progressive multiple sclerosis, or progressive-relapsing multiple sclerosis.
5 . The method of claim 1 , wherein the disease or condition is central pontine myelinolysis, acute disseminated encephalomyelitis, Balo concentric sclerosis, Marburg multiple sclerosis, tumefactive multiple sclerosis, diffuse myelinoclastic sclerosis, acute hemorrhagic leukoencephalitis, neuromyelitis optica, a chronic inflammatory demyelinating polyneuropathy, Leber hereditary optic neuropathy, multifocal motor neuropathy, paraproteinemic demyelinating polyneuropathy, tropical spastic paraparesis, a Guillain-Barré syndrome, infantile Refsum disease, adult Refsum disease 1, adult Refsum disease 2, Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy, Krabbe disease, Pelizaeus-Merzbacher disease, Canavan disease, Alexander disease, peroneal muscular atrophy, cerebrotendineous xanthomatosis, Binswanger's disease, leukoencephalopathy with vanishing white matter, toxic leukoencephalopathy, van der Knaap disease, progressive multifocal leukoencephalopathy, Marchiafava-Bignami disease or transverse myelitis.
6 . The method of claim 5 , wherein the X-linked adrenoleukodystrophy is adrenomyeloneuropathy or Addison's disease.
7 . The method of claim 1 , wherein the disease or condition is a chronic axonal neuropathy.
8 . The method of claim 1 , wherein the disease or condition results from intraventricular hemorrhage, neonatal hypoxia, or acute hypoxemic respiratory failure.
9 . The method of claim 1 , wherein the disease or condition is cerebral palsy.
10 . The method of claim 1 , wherein administration of the sobetirome or pharmaceutically acceptable salt thereof prevents or mitigates at least one symptom of the disease or condition.
11 . The method of claim 10 , wherein the symptom is a lack of sphincter control, erectile dysfunction, paraparesis, ataxia, adrenocortical insufficiency, progressive neuropathy, paresthesia, dysarthria, dysphagia, clonus, or any combination thereof.
12 . The method of claim 1 , wherein administration of the sobetirome or pharmaceutically acceptable salt thereof prevents or mitigates damage to central nervous system myelin, peripheral nervous system myelin, adrenal cortex, testicular Leydig cells, or any combination thereof.
13 . The method of claim 1 , wherein the sobetirome, or pharmaceutically acceptable salt thereof, is administered orally, parenterally, or topically.
14 . The method of claim 13 , wherein the sobetirome, or pharmaceutically acceptable salt thereof, is administered orally.
15 . The method of claim 14 , wherein the sobetirome, or pharmaceutically acceptable salt thereof, is administered enterally, buccally, sublingually, sublabially, or by inhalation.
16 . The method of claim 13 , wherein the sobetirome, or pharmaceutically acceptable salt thereof, is administered parenterally.
17 . The method of claim 16 , wherein the sobetirome, or pharmaceutically acceptable salt thereof, is administered intra-arterially, intravenously, intraventricularly, intramuscularly, subcutaneously, intraspinally, intraorbitally, or intracranially.
18 . The method of claim 1 , wherein the sobetirome or pharmaceutically acceptable salt thereof is administered at a dose of about 1 μg to about 500 μg daily, or about 10 μg to about 100 μg daily.
19 . The method of claim 1 , wherein the disease or condition is not X-ALD, is not multiple sclerosis, or is not cerebral palsy, or any combination thereof.
20 . A method of treating a patient having or at risk of developing multiple sclerosis administering to the patient 1 mg/kg/day of sobetirome, or a pharmaceutically acceptable salt thereof.