Use of mannose 6 phosphate and modifications thereof for memory enhancement and reducing memory impairment
Inventors
ALBERINI, CRISTINA MARIA • Trauner, Dirk • ARP, CHRISTOPHER JAMES
Assignees
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Publication Number
US-12491203-B2
Publication Date
2025-12-09
Expiration Date
Abstract
Provided are compositions and methods for memory enhancement, including recovery of memory impairment. The compositions and methods relate to mannose-6-phosphate and derivatives of mannose-6-phosphate. The methods relate to administration of M6P or derivatives thereof to individuals in whom memory enhancement is desired.
Core Innovation
The invention provides compositions and methods for enhancing memory in a subject in whom enhancement of memory is desired. The method includes administering a therapeutically effective amount of a compound having a specified structure and/or a pharmaceutically acceptable salt. The therapeutic concept is directed to memory enhancement and to reducing memory impairment.
The compound is described as mannose-6-phosphate (M6P; L1) or derivatives, including modifications as agonists/activators of the IGF-2 receptor other than IGF-2. The compound scope includes structurally defined L-series derivatives (L2-L9) with modifications described for carbon 1 and/or carbon 6, and includes pharmaceutically acceptable salts.
The disclosed therapeutic benefit is described as increased retention/recall and/or reduced decay of memory, including memory enhancement and reversal in animal models using M6P/L1 and a phosphonate derivative (PnM6P; L2) across multiple memory paradigms and time points.
Claims Coverage
The independent claim covers administering a therapeutically effective amount of a structurally defined M6P (L1) and/or M6P-derivative compound (including pharmaceutically acceptable salts) to enhance memory. The dependent claims add multiple inventive feature constraints, including dosage range limits, measurement of memory outcomes, clinical context narrowing, and structural/binding specificity constraints for the L2 derivative.
Administering a therapeutically effective M6P-structured compound for memory enhancement
A method for enhancing memory in a subject by administering to a subject in whom enhancement of memory is desired, a composition comprising a therapeutically effective amount of a compound having the following structure, and/or a pharmaceutically acceptable salt thereof.
Memory enhancement measured by retention of memory and/or duration of memory
Enhancement of memory is assessed as retention of memory and/or duration of memory.
Therapeutically effective dosage range of 1 to 2000 µg/kg
The compound is administered in an amount in the range of 1 to 2,000 µg/kg body weight.
Neurodegenerative disease selection for targeted memory enhancement
The neurodegenerative disease is selected from Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).
Non-conjugated L2 structural constraint
L2 is not conjugated to another moiety.
L2 as the only agent specifically binding IGF-2 receptor
L2 is the only agent in the composition that specifically binds to IGF-2 receptor.
Overall claim coverage is centered on administering a therapeutically effective amount of a structurally defined M6P (and/or pharmaceutically acceptable salt) for memory enhancement, with dependent claims further constraining assessment metrics, dosage range, selected neurodegenerative diseases, and structural/binding specificity for the L2 derivative.
Stated Advantages
Increased retention/recall of memory.
Reduced decay of memory.
Memory enhancement and reversal in animal models.
Documented Applications
Memory enhancement and reversal in animal models using novel object recognition paradigms.
Memory enhancement and reversal in animal models using contextual fear memory paradigms.
Memory enhancement and reversal in animal models using inhibitory avoidance paradigms.
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