Use of BGP15 to treat familial dysautonomia
Inventors
LEFCORT, Frances Brenda • BROWNSTEIN, Michael Jay
Assignees
Montana State University Bozeman • N-Gene Research Laboratories Inc
Publication Number
US-10702514-B2
Publication Date
2020-07-07
Expiration Date
2037-06-29
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Abstract
Disclosed is the use of O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidoxime (BGP15), its tautomers, enantiomers and pharmaceutically acceptable salts thereof for the treatment of Familial Dysaustonomia.
Core Innovation
The invention relates to the use of O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidoxime (BGP15), including its tautomers, enantiomers, and pharmaceutically acceptable salts, for treating familial dysautonomia (FD). The inventors have discovered that BGP15 unexpectedly provides benefit in the treatment of FD by targeting neuronal deficits associated with the disease.
Familial dysautonomia is a hereditary sensory and autonomic neuropathy mainly observed in individuals of Ashkenazi descent, characterized by symptoms including insensitivity to pain, unstable blood pressure, growth issues, chronic lung and kidney diseases, optic neuropathy, and shortened lifespan. The disorder is caused by a mutation in the IKBKAP gene, leading to tissue-specific reduction of the IKAP protein. Current treatments address only the symptoms, not the underlying neuronal pathology, and there is an urgent need for a therapy that modulates the effects of IKAP deficiency.
Studies described in the invention used both cellular and animal models of FD, specifically the IKBKAP conditional knock-out mouse (Wnt1-cre:Ikbkap−/−). In these models, BGP15 was shown to decrease the death of sensory neurons both in vitro and in vivo, improve mitochondrial function, restore mitochondrial membrane potential and network morphology, and significantly enhance cardiac innervation. Thus, the invention provides a method for modulating neuronal deficits and mitochondrial dysfunction underlying familial dysautonomia through administration of BGP15.
Claims Coverage
There is one independent claim, which defines the principal inventive feature of the patent.
Method of treating familial dysautonomia using BGP15
The main inventive feature is a method for treating familial dysautonomia in a subject by administering an effective amount of O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidoxime (BGP15), including its tautomers, enantiomers, and pharmaceutically acceptable salts. - The method specifies the disease being treated (familial dysautonomia). - The compound to be administered is structurally defined as BGP15 and its related forms. - The claim encompasses administration to any subject in need of such treatment.
The independent claim provides coverage for the use of BGP15 and its derivatives in the treatment of familial dysautonomia.
Stated Advantages
BGP15 is able to rescue impaired mitochondrial function in familial dysautonomia neurons and mitigate the effects of the disease at a neuronal level.
Treatment with BGP15 decreases neuronal cell death in both in vitro and in vivo models relevant to familial dysautonomia.
Administration of BGP15 improves cardiac innervation in animal models of familial dysautonomia.
Documented Applications
Use of BGP15 and its tautomers, enantiomers, and pharmaceutically acceptable salts for the treatment of familial dysautonomia.
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