Methods and compositions for the treatment of symptoms of prion diseases

• US 10,413,601 B2
• Filed: 05/11/2017
• Issued: 09/17/2019
• Est. Priority Date: 10/03/2008
• Status: Active Grant

• Current Assignee: Curemark LLC
• Original Assignee: Curemark LLC
• Inventors: Fallon, Joan M.
• Primary Examiner(s): Ariani, Kade
• Application Number:
  US15/593,129
• Publication Number:
  US 20180078623A1
• Time in Patent Office: 859 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 36/185 Magnoliopsida (dicotyledons)
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 38/4873 Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
• CPC Class Codes: A61K 38/54 Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
• CPC Class Codes: C12Q 1/37 involving peptidase or proteinase
• CPC Class Codes: C12Y 301/01 Carboxylic ester hydrolases (3.1.1)
• CPC Class Codes: C12Y 302/01 Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
• CPC Class Codes: C12Y 304/00 Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
• CPC Class Codes: C12Y 304/21001 Chymotrypsin (3.4.21.1)
• CPC Class Codes: C12Y 304/21004 Trypsin (3.4.21.4)
• CPC Class Codes: C12Y 304/22002 Papain (3.4.22.2)
• CPC Class Codes: G01N 2333/976 Trypsin; Chymotrypsin
• CPC Class Codes: G01N 2800/2828 Prion diseases
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

A therapeutic composition for the treatment of the symptoms of prion diseases and the method for preparing the therapeutic agents is disclosed. The therapeutic composition is a stable pharmaceutical composition comprising one or more digestive and/or pancreatic enzymes. The therapeutic composition may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic composition may be made orally, through injection, by adherence of a medicated patch or other method. Further, a method of using fecal chymotrypsin level as a biomarker for the presence of a prion disease, or the likelihood of an individual to develop a prion disease is disclosed.

Claims

1. A method of identifying a subject with an infectious prion disease that can be treated with digestive enzymes, the method comprising:

obtaining a fecal sample from the subject;

measuring a level of fecal chymotrypsin (FCT) present in the fecal sample using an enzymatic photospectrometry method; and

thereby determining that the subject having the prion disease will benefit from administration of a composition that comprises digestive enzymes when the level of fecal chymotrypsin is 8.4 U/gram or less, wherein the prion disease is not Fatal Familial Insomnia.

2. The method of claim 1, wherein the infectious prion disease comprises Gerstmann-Strä

ussler-Scheinker Syndrome.

3. The method of claim 1, wherein the infectious prion disease comprises a Creutzfeldt-Jakob Disease, and the Creutzfeldt-Jakob Disease comprises an iatrogenic Creutzfeldt-Jakob Disease, or a variant Creutzfeldt-Jakob Disease.

4. The method of claim 1, further comprising administering the subject an of a pharmaceutical composition that comprises digestive enzymes.

5. The method of claim 4, wherein the pharmaceutical composition is a dosage formulation selected from the group consisting of a pill, a tablet, a capsule, a microcapsule, a mini-capsule, a time-released capsule, a mini-tab, a sprinkle, and a combination thereof.

6. The method of claim 4, wherein the digestive enzymes comprise a protease, an amylase, and a lipase.

7. The method of claim 4, wherein the pharmaceutical composition further comprises one or more enzymes selected from the group consisting of a cellulase, a sucrase, a maltase, a papaya, and a papain.

8. The method of claim 4, wherein the digestive enzymes comprise pancreatic enzymes.

9. The method of claim 4, wherein the digestive enzymes are, independently, animal enzymes, microbial enzymes, plant enzymes, or synthetically-prepared enzymes.

10. The method of claim 9, wherein the digestive enzymes comprise animal enzymes derived from a pig.

11. The method of claim 4, wherein the pharmaceutical composition comprises at least one amylase, a mixture of proteases comprising chymotrypsin and trypsin, at least one lipase, and papain.

12. The method of claim 6, wherein a ratio of total protease to total lipase in U.S.P. units in the pharmaceutical composition ranges from about 1:

1 to about 20;

1.

13. The method of claim 12, wherein the ratio of total protease to total lipase in U.S.P. units in the pharmaceutical composition ranges from about 4:

1 to about 10;

1.