Alkaline phosphatase agents for treatment of neurodevelopmental disorders
Inventors
Kaleko, Michael • FURLAN FREGUIA, Christian • Connelly, Sheila
Assignees
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Publication Number
US-11338020-B2
Publication Date
2022-05-24
Expiration Date
Abstract
Compositions and methods, including therapeutic alkaline phosphatases that find use in the treatment or prevention of various neurodevelopmental diseases or disorders, are described.
Core Innovation
The invention relates to therapeutic alkaline phosphatase (AP) agents and pharmaceutical compositions for preventing or treating neurodevelopmental disorders. The approach targets an unborn child by administering a bovine intestinal alkaline phosphatase (bIAP) agent to a mother at risk.
The disclosed methods emphasize preventing or treating autism spectrum disorder (ASD) in an unborn/newborn child through maternal administration of bIAP. The mother is characterized by gastrointestinal dysbiosis, obesity, metabolic syndrome, gut-mediated systemic inflammation, and/or leaky gut.
The bIAP agents include mammalian intestinal/bovine IAP and related forms, with embodiments described using sequences identified as SEQ ID NOs, including hIAP, bIAP II, and bIAP IV. Performance and formulation attributes are described in terms of activity and gastrointestinal stability, including pH stability and chyme stability.
Claims Coverage
Two independent claims are identified. Each claim requires maternal administration of a bovine intestinal alkaline phosphatase (bIAP) to treat or prevent a neurodevelopmental disorder in an unborn child, with each independent claim further narrowing the disorder scope and bIAP composition requirements.
Maternal bIAP administration to an unborn child for neurodevelopmental disorder prevention or treatment
A method of treating or preventing a neurodevelopmental disorder in an unborn child comprising administering to the subject an effective amount of a bovine intestinal alkaline phosphatase (bIAP) agent, wherein the neurodevelopmental disorder is selected from autism spectrum disorder (ASD), schizophrenia, attention deficit hyperactivity disorder (ADHD), schizoaffective disorder, and bipolar affective disorder.
Maternal condition-restricted bIAP treatment of ASD using high sequence identity bIAP
A method of treating or preventing autism spectrum disorder (ASD) in an unborn child comprising administering to the mother an effective amount of a bovine intestinal alkaline phosphatase (bIAP), wherein the mother is afflicted with one or more of gastrointestinal dysbiosis, obesity, metabolic syndrome, gut-mediated systemic inflammation, and leaky gut, and wherein the bovine IAP comprises an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 2 or SEQ ID NO: 3.
Across the independent claims, the inventive concept is maternal administration of bIAP to an unborn child to prevent or treat neurodevelopmental disorders, with one claim covering multiple disorder types and the other claim narrowing to ASD with specified maternal gut/metabolic conditions and requiring high sequence identity (at least 97%) to SEQ ID NO: 2 or SEQ ID NO: 3.
Stated Advantages
Reduced social deficits in offspring compared to high fat vehicle controls.
Social behavior patterns in offspring closer to normal controls.
Documented Applications
Use of SYN BIAPII (bovine intestinal alkaline phosphatase II) in an autism-relevant mouse model with maternal regular chow or high fat diet and offspring behavioral testing including three-chamber social interaction, reciprocal social interaction, open field metrics, and jumping/repetitive measures.
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