IP Library › Granted Patent US 12,397,004
Granted Patent B2
US 12,397,004 · App. 17/290,798 · Granted Aug 26, 2025

Nasal delivery of low-dose aspirin for the treatment of neurodegenerative and lysosomal storage diseases

Inventor: Kalipada Pahan (Skokie, IL)
Assignee: Rush University Medical Center
A61K31/616A61K9/0043A61K9/0078A61P25/28
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,397,004
App. No.
17/290,798
Granted
Aug 26, 2025
Kind
B2
Abstract

Provided herein are methods for delivering acetylsalicylic acid via nasal delivery for the treatment of neurodegenerative and lysosomal storage disorders, such as Alzheimer's disease and Batten disease.

Claims (8)

1. A method of treating a neurodegenerative disorder in a subject in need thereof, the method comprising administering a therapeutically effective amount of acetylsalicylic acid to the subject via nasal delivery, wherein the therapeutically effective amount is 0.1 mg/kg/d to 1 mg/kg/d of acetylsalicylic acid and wherein the neurodegenerative disorder is selected from the group consisting of Multiple Sclerosis, Experimental Allergic Encephalomyelitis (EAE), Alzheimer's disease, Parkinson's disease, and Huntington's disease.

2. The method of claim 1 , wherein the acetylsalicylic acid is formulated to be a propellant-free inhalable solution.

3. The method of claim 2 , wherein the propellant-free inhalable solution is administered to the subject via a nebulizer.

4. The method of claim 2 , wherein the propellant-free inhalable solution is administered to the subject via nasal inhalation.

5. A method of treating a lysosomal storage disorder in a subject in need thereof, the method comprising administering a therapeutically effective amount of acetylsalicylic acid to the subject via nasal delivery, wherein the therapeutically effective amount is 0.1 mg/kg/d to 1 mg/kg/d of acetylsalicylic acid and wherein the lysosomal storage disorder is selected from the group consisting of Batten disease, Neimann-Pick disease, Krabbe disease, and Tay-Sachs disease.

6. The method of claim 5 , wherein the acetylsalicylic acid is formulated to be a propellant-free inhalable solution.

7. The method of claim 6 , wherein the propellant-free inhalable solution is administered to the subject via a nebulizer.

8. The method of claim 6 , wherein the propellant-free inhalable solution is administered to the subject via inhalation.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2025
From: PAHAN, KALIPADA
To: RUSH UNIVERSITY MEDICAL CENTER
Reel/Frame 070901/0864 →
CONFIRMATORY LICENSE Recorded Jan 23, 2024
From: RUSH UNIVERSITY MEDICAL CENTER
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066365/0136 →
Continuity (2)
Provisional Application 62755695 · Nov 5, 2018
Related Publication 20210401856A1 · Dec 30, 2021
References Cited (44)
US 4885287A · Hussain · 1989 [cited by examiner]
US 20020025917A1 · Pappalardo · 2002 [cited by applicant]
US 20140322328A1 · Yadidi · 2014 [cited by applicant]
US 20150359851A1 · Stankovic et al. · 2015 [cited by applicant]
US 20170027963A1 · Crowley et al. · 2017 [cited by applicant]
US 20170354666A1 · Pahan · 2017 [cited by applicant]
EP 0504263A1 · 1992 [cited by applicant]
McLean, Journal of Allergy and Clinical Immunology, vol. 72, Issue 2, 1983, pp. 187-192 (Year: 1983). [cited by examiner]
Chen et al., Frontiers in Aging Neuroscience, vol. 6, Article 7, 2014 (Year: 2014). [cited by examiner]
Bohnen et al., White matter lesions in Parkinson disease. Nat Rev Neurol. Apr. 2011;7(4):229-36 (Year: 2011). [cited by examiner]
Smith et al., Neurobiology of Disease, vol. 36, Issue 2, 2009, pp. 242-251 (Year: 2009). [cited by examiner]
Aubin N., Curet O., Deffois A., Carter C. (1998) Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem, 71, 1635-1642. [cited by applicant]
Berk M., Dean O., Drexhage H., McNeil J.J., Moylan S., O'Neil A., Davey C.G., Sanna L., Maes M. (2013) Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med, 11, 74. [cited by applicant]
Chandra, S., Malabendu J., Pahan K. (2018) Aspiring induces Lysosomal biogenesis and attenuates Amyloid plaque pathology in a mouse model of Alzheimer's disease via a PPARα. J Neuroscience, 0054-18; DOI: https://doi.org… [cited by applicant]
Dai Y., Ge J. (2012) Clinical use of aspirin in treatment and prevention of cardiovascular disease. Thrombosis. 2012; 2012: 245037. Published online Nov. 2, 20114. doi: [10.1155/2012/245037]. [cited by applicant]
De Duve, C. and Wattiaux, R. (1966) Functions of lysosomes. Annu Rev Physiol, 28, 435-492. [cited by applicant]
Djupesland, P.G. (2013) Nasal drug delivery devices: characteristics and performance in a clinical perspective—a review. Drug Deliv Transl Res. 3(1), 42-62. [cited by applicant]
Djupesland, P.G., Messina J.C., Mahmoud, R.A. (2014) The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. Therapeutic Delivery, 5(6), 709-733. [cited by applicant]
El-Behi, M., Rostami, A., and Ciric, B. (2010) Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol, 5, 189-197. [cited by applicant]
Green GA (2001) Understanding NSAIDs: from aspirin to COX-2. Clin Cornerstone, 3, 50-60. [cited by applicant]
International Preliminary Report on Patentability, issued in PCT/US2019/059794, dated May 11, 2021. [cited by applicant]
International Search Report, issued in PCT/US2019/059794, dated Jan. 21, 2020. [cited by applicant]
Lanas A., and Scheiman J. (2007) Low-dose aspirin and upper gastrointestinal damage: epidemiology, prevention and treatment. Curr Med Res Opin., 23(1), 163-73. [cited by applicant]
Miyake et al., “The Blood-Brain Barrier and Nasal Drug Delivery to the Central Nervous System,” American Journal of Rhinology & Allergy, vol. 29, Issue 2, (2015), pp. 124-127. [cited by applicant]
Mondal, S., Jana, M., Dasarathi, S., Roy, A., and Pahan, K. (2018) Low-dose aspirin ameliorates experimental allergic encephalomyelitis through interleukin-11-mediated protection of regulatory T cells. Sci. Signal., vol… [cited by applicant]
Moyad M.A. (2001) An introduction to aspirin, NSAids, and COX-2 inhibitors for the primary prevention of cardiovascular events and cancer and their potential preventive role in bladder carcinogenesis: part II. Semin Uro… [cited by applicant]
Nagelschmitz et al., “First-in-Man Dose Escalation Study of Aspirin® Inhaled for the Clinical Development of a New Antiviral Treatment of Resistant Influenza,” Clinical Therapeutics, vol. 37, Issue 8, Suppl. (2015), p. … [cited by applicant]
Nilsson S.E., Johansson B., Takkinen S., Berg S., Zarit S., McClearn G., Melander A. (2003) Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged > or =80. Eur J Clin Pharm… [cited by applicant]
Patel, D., Roy, A., Kundu, M., Jana, M., Luan, C.H., Gonzalez, F.J., and Pahan, K. (2018). Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory. Proc Natl Acad Sci, 115, E7408-E7417. [cited by applicant]
Perez-Sala et al. “The C-Terminal Sequence of RhoB Directs Protein Degradation through an Endo-Lysosomal Pathway,” PLOS One, vol. 4, Issue 12, (2009), pp. 1-14. [cited by applicant]
Rangasamy, S. B., Dasarathi, S., Pahan, P., Jana, M., and Pahan, K. (2018) Low-dose aspirin upregulates tyrosine hydroxylase and increases dopamine production in dopaminergic neurons: Implications for Parkinson's diseas… [cited by applicant]
Rangasamy, S.B., Corbett, G.T., Roy, A., Modi, K.K., Bennett, D.A., Mufson, E.J., Ghosh, S., and Pahan, K. (2015) Intranasal Delivery of NEMO-Binding Domain Peptide Prevents Memory Loss in a Mouse Model of Alzheimer's D… [cited by applicant]
Rizwan S., Idrees A., Ashraf M., Ahmed T. (2016) Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model. Exp Ther Med, 11, 1961-1970. [cited by applicant]
Rothwell P.M., Wilson M., Price J.F., Belch J.F., Meade T.W., Mehta Z. (2012) Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet, 379, 1591-1601. [cited by applicant]
Roy, A., Jana, M., Corbett, G.T., Ramaswamy, S., Kordower, J.H., Gonzalez, F.J., and Pahan, K. (2013) Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator… [cited by applicant]
Roy, A., Jana, M., Kundu, M., Corbett, G.T., Rangaswamy, S.B., Mishra, R.K., Luan, C.H., Gonzalez, F.J., and Pahan, K. (2015) HMG-CoA Reductase Inhibitors Bind to PPARα to Upregulate Neurotrophin Expression in the Brain… [cited by applicant]
Sakaguchi, S. (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol, 6, 345-352. [cited by applicant]
Sakaguchi, S., and Powrie, F. (2007) Emerging challenges in regulatory T cell function and biology. Science, 317, 627-629. [cited by applicant]
Sestini et al., “Different Effects of Inhaled Aspirinlike Drugs on Allergen-Induced Early and Late Asthmatic Responses,” Am J Respir Crit Care Med., vol. 159, (1999), pp. 1228-1233. [cited by applicant]
Shi, G., Cox, C.A., Vistica, B.P., Tan, C., Wawrousek, E.F., and Gery, I. (2008) Phenotype switching by inflammation-inducing polarized Th17 cells, but not by Th1 cells. J Immunol, 181, 7205-7213. [cited by applicant]
Soleti et al., “Aspirin Inhalation Treatment for COPD Patients: Preliminary Studies on PK and Inflammatory Biomarkers,” European Respiratory Journal, vol. 38, Suppl. 55, (2011), p. 825. [cited by applicant]
Sostres, C., Lanas, AI. (2011) Gastrointestinal effects of aspirin. Nat Rev Gastroenterol Hepatol, 8(7), 385-94. [cited by applicant]
“Abstracts from the Joint Meeting of the International Society for NeuroVirology (ISNV) and the Society on Neuroimmune Pharmacology (SNIP) Apr. 10-14, 2018, Chicago, Illinois, USA”, Journal of Neurovirology, Informa Hea… [cited by applicant]
Extended European Search Report for European Application No. 19882244.7 dated Jun. 21, 2022. [cited by applicant]