Methods of treating Parkinson's disease using aminosterols and compositions comprising the same
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Publication Number
US-10633413-B2
Publication Date
2020-04-28
Expiration Date
Abstract
This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminosterol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias, or derivatives thereof, to a subject in need.
Core Innovation
The document describes orally administered aminosterols, including Aminosterol 1436, as therapeutics for Parkinson’s disease. It also describes orally administered squalamine and other aminosterol variants and derivatives, and frames the response as an “Aminosterol-Induced GI Response.” The response is characterized as controlled activation of the intestinal enteric nervous system, with downstream effects relevant to neurodegeneration.
The problem described is that neurodegenerative diseases, including Parkinson’s disease, involve alpha-synuclein accumulation and related symptoms, including onset, development, or advancement. The document connects the intestinal secretory response and intestinal enteric nervous system signaling to potential modulation of neurodegenerative processes.
Mechanistically, the document states that aminosterol activity is associated with alpha-synuclein displacement in neurons, including an effect described as displacing alpha-synuclein accumulation. The document also describes supporting evidence including GI behavior changes after oral dosing, a mesenteric nerve activation study supporting enteric-to-CNS signaling, and in vitro alpha-synuclein displacement.
Claims Coverage
The independent claim covers one core therapeutic concept: orally administering a pharmaceutically acceptable aminosterol composition specifically containing Aminosterol 1436, or a pharmaceutically acceptable salt or derivative, in a therapeutically effective amount to treat Parkinson’s disease. Dependent claims add co-administration with squalamine, alpha-synuclein accumulation prevention, oral bloodstream level targeting after dosing, and specific oral formulation disintegration and dissolution-rate requirements.
Oral aminosterol therapy for Parkinson’s disease with Aminosterol 1436
A method of treating Parkinson’s disease in a subject comprising orally administering a therapeutically effective amount of a pharmaceutically acceptable grade aminosterol composition, wherein the aminosterol is Aminosterol 1436, or a pharmaceutically acceptable salt or derivative thereof.
Co-administration of squalamine and Aminosterol 1436
Administering to the subject a combination of pharmaceutically acceptable squalamine and pharmaceutically acceptable Aminosterol 1436, with the two components provided in the same or separate compositions.
Preventing alpha-synuclein accumulation to prevent or slow progression
Preventing the accumulation of alpha synuclein to prevent or slow onset, development, or advancement of Parkinson’s disease or related symptoms.
Oral dosing with targeted low bloodstream levels after administration
Following oral administration, achieving less than about 10 ng/ml of the administered aminosterol in the subject’s bloodstream measured between about 1 to about 12 hours.
Oral dosage-form disintegration and dissolution-rate for intended therapeutic benefit
Formulating the composition into an oral liquid, capsule, or tablet that disintegrates in the stomach, upper small intestine, or more distal portions with a dissolution rate appropriate to achieve intended therapeutic benefit.
Across the claim set, the inventive coverage centers on oral treatment of Parkinson’s disease using Aminosterol 1436, or its salt or derivative, optionally in combination with squalamine. Additional inventive features include preventing alpha-synuclein accumulation, achieving targeted low bloodstream levels after oral dosing, and formulating an oral dosage form with specified disintegration location and dissolution-rate appropriate to intended therapeutic benefit.
Stated Advantages
Treating Parkinson’s disease in a subject.
Preventing or slowing onset, development, or advancement of Parkinson’s disease or related symptoms through preventing alpha-synuclein accumulation.
Achieving low bloodstream levels (less than about 10 ng/ml) of the administered aminosterol following oral administration.
Documented Applications
Treating Parkinson’s disease in a subject through oral administration of a therapeutically effective amount of a composition comprising Aminosterol 1436, or a pharmaceutically acceptable salt or derivative.
Preventing or slowing progression of Parkinson’s disease or related symptoms by preventing accumulation of alpha synuclein.
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