Treatment and prevention of alzheimer's disease (AD)
Inventors
Mandler, Markus • Schneeberger, Achim • Zauner, Wolfgang • Von Bonin, Arne • Mattner, Frank • Schmidt, Walter
Assignees
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Publication Number
US-11065273-B2
Publication Date
2021-07-20
Expiration Date
Abstract
The invention discloses an aluminium salt for use in the treatment and prevention of dementias associated with β-amyloid deposition, preferably AD.
Core Innovation
The invention relates to a disease-modifying treatment and prevention for dementias associated with β-amyloid deposition by administering to a subject in need thereof a composition comprising an effective amount of at least one aluminium salt as the sole active ingredient. The approach is positioned for dementias associated with β-amyloid deposition, especially Alzheimer's disease. The disclosed rationale contrasts prior Alzheimer’s disease trial failures with a proposed mechanism described as APP/β-independent, supported by animal APP-transgenic Tg2576 data showing cognitive improvement without significant Aβ level change.
The disclosed aluminium-salt compositions are defined using chemical general formula notation for aluminium salts and include preferred aluminium oxyhydroxide forms such as Alhydrogel and related examples such as AdjuPhos. The formulation is described to use a high-purity preparation with low heavy metal content and anion-free character, and to be provided as a suspension. A specified suspension pH range is disclosed, together with other formulation characteristics described in the partial content.
Clinical-trial evidence described in the partial content includes a randomized placebo-controlled phase II study (AFF006) in early Alzheimer's disease, in which aluminium salt is administered in dose amounts exceeding a threshold referenced to 21 C.F.R. 610.15. Efficacy is described using an adapted ADAS-cog/ADCS-ADL composite score and an MRI biomarker (right hippocampus volume), and the partial content reports a statistically significant disease-modifying effect with correlations between clinical and radiologic biomarkers as well as caregiver quality-of-life improvements. Local reaction frequency is described as increasing with dose.
Additional supportive experiments described in the partial content include comparisons of Aβ-targeting vaccines versus alum-only conditions and assessments that include contextual fear conditioning and amyloid load measurements, together with immunogenicity and inflammatory-related readouts described at a conceptual level. The partial content also provides contextual discussion of prior approaches and frames the disclosed aluminium-salt strategy as an alternative disease-modifying approach for dementias associated with β-amyloid deposition.
Claims Coverage
The independent claim set centers on a method for reducing the severity of a dementia associated with β-amyloid deposition by administering a dose-form composition comprising at least one aluminium salt as the sole active ingredient, in an amount exceeding an Apr. 2013 threshold referenced to 21 C.F.R. 610.15. Dependent claims further define the dementia subtype, aluminium-salt structure, suspension pH range, administration routes, and dosing frequency/duration schedules. The inventive features below reflect these main claim refinements.
Reducing dementia severity by aluminium salt as sole active ingredient above regulatory threshold
A method for reducing the severity of a dementia associated with β-amyloid deposition comprising administering to a subject in need thereof a composition comprising an effective amount of at least one aluminium salt as the sole active ingredient in a dose form of an amount exceeding an amount prescribed in the US general biological products standards of 21 C.F.R. 610.15, as of Apr. 2013.
Alzheimer's disease dementia associated with β-amyloid deposition
The dementia associated with β-amyloid deposition is Alzheimer's Disease (AD).
Aluminium salt structure defined by chemical general formula
The aluminium salt conforms to Me_aAl_b^3+An_c·nH2O with specified allowed Me+, An, and parameter ranges.
Suspension pH range
The composition is a suspension having a pH ranging from 4 to 10.
Specific administration routes
Administration is performed subcutaneously, intranodally, intradermally, or intramuscularly.
Dosing frequency and minimum treatment duration schedule
The composition is administered at least twice a month for at least six months.
Across the independent claim and its dependents, the coverage is directed to reducing the severity of dementia associated with β-amyloid deposition by administering a composition where aluminium salt is the sole active ingredient and the administered amount exceeds the Apr. 2013 threshold referenced to 21 C.F.R. 610.15, with further narrowing to Alzheimer's disease, a defined aluminium-salt chemical general formula, a suspension pH of 4 to 10, specified administration routes, and at-least-twice-monthly dosing for at least six months.
Stated Advantages
Claims-supported reduction of the severity of dementia associated with β-amyloid deposition.
Disease-modifying effect assessed with an adapted ADAS-cog/ADCS-ADL composite score and an MRI biomarker (right hippocampus volume), with correlations between clinical and radiologic biomarkers.
Caregiver quality of life improvements are reported.
Documented Applications
Disease-modifying treatment and prevention for dementias associated with β-amyloid deposition, especially Alzheimer's disease.
Use in a randomized placebo-controlled phase II AFF006 framework in early Alzheimer's disease with efficacy assessment using an adapted ADAS-cog/ADCS-ADL composite score and MRI hippocampus volume.
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