Methods and compositions for the treatment of symptoms of prion diseases

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 for treating a prion disease in a patient diagnosed with the prion disease, the method comprising administering to the patient a pharmaceutical composition that comprises digestive enzymes, wherein the digestive enzymes comprise a protease, an amylase and a lipase, whereby one or more symptoms of the prion disease are treated; wherein said patient diagnosed with the prion disease has a subnormal level of fecal chymotrypsin, wherein the one or more symptoms comprise a personality change, a psychiatric problem, lack of coordination, unsteady gait, myoclonus, an unusual sensation, insomnia, confusion, a memory problem, severe mental impairment, loss of the ability to move or speak, or a combination thereof.

2. The method of claim 1, wherein the pharmaceutical composition further comprises one or more enzymes selected from the group consisting of a cellulase, a sucrase, and a maltase.

3. The method of claim 1, wherein the digestive enzymes are pancreatic enzymes.

4. The method of claim 1, wherein the protease is chymotrypsin or trypsin.

5. The method of claim 1, wherein the digestive enzymes are animal enzymes, microbial source enzymes, plant enzymes, or are synthetically prepared enzymes.

6. The method of claim 1, wherein the amylase is present in the pharmaceutical composition in an amount of from about 10,000 to about 60,000 United States Pharmacopeia (U.S.P) units per dose.

7. The method of claim 1, wherein the protease and the lipase in the pharmaceutical composition in U.S.P. units are present in a ratio of from about 1:1 to about 20:1.

8. The method of claim 7, wherein the ratio of protease to lipase is from about 4:1 to about 10:1.

9. The method of claim 1, 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.

10. The method of claim 1, wherein the subnormal level of fecal chymotrypsin level is 8.4 U/gram or less.

11. The method of claim 1, wherein the protease is present in the pharmaceutical composition in an amount of from about 10,000 to about 70,000 U.S.P units per dose.

12. The method of claim 1, wherein the lipase is present in the pharmaceutical composition in an amount of from about 4,000 to about 30,000 U.S.P. units per dose.

13. The method of claim 4, wherein the protease is chymotrypsin, and wherein the chymotrypsin is present in the pharmaceutical composition in an amount of from about 2 to about 5 mg per dose.

14. The method of claim 4, wherein the protease is trypsin, and wherein the trypsin is present in the pharmaceutical composition in an amount of from about 60 to about 100 mg per dose.

Description

DETAILED DESCRIPTION

(1) The present disclosure provides pharmaceutical compositions and methods for treating symptoms associated with CRPS, Pervasive Development Disorders, and Dysautonomias. The pharmaceutical compositions described herein include one or more digestive enzymes, which are postulated by the present inventor to assist in proper digest protein and thus to ameliorate the gastrointestinal dysfunction that is associated with the described disorders.

(2) In certain embodiments, the pharmaceutical compositions may include one or more digestive enzymes, wherein the one or more digestive enzymes comprise at least one lipase and at least one protease, and wherein the ratio of total proteases to total lipases (in USP units) ranges from about 1:1 to about 20:1. In some cases, the ratio of total proteases to total lipases ranges from about 4:1 to about 10:1.

(3) In some cases, a pharmaceutical composition for use herein comprises at least one amylase, at least one protease, and at least one lipase. In certain embodiments, the pharmaceutical composition includes multiple proteases, including, without limitation, chymotrypsin and trypsin. In certain embodiments, the composition can further include one or more hydrolases, papain, bromelain, papaya, celluloses, pancreatin, sucrases, and maltases.

(4) The one or more enzymes can be independently derived from animal, plant, microbial, or synthetic sources. In some embodiments, the one or more enzymes are derived from pig, e.g.: pig pancreas.

(5) One exemplary formulation for the treatment of the symptoms of prion diseases is as follows:

(6) Amylase 10,000-60,000 U.S.P

(7) Protease 10,000-70,000 U.S.P

(8) Lipase 4,000-30,000 U.S.P

(9) Chymotrypsin 2-5 mg

(10) Trypsin 60-100 mg

(11) Papain 3,000-10,000 USP units/mg

(12) Papaya 30-60 mg

(13) Additional formulations comprising one or more digestive enzymes may be advantageous including formulations in which the ratio of total proteases to total lipases (in USP units) is from about 1:1 to about 20:1. In some embodiments, the ratio of total proteases to total lipases is from about 4:1 to about 10:1. Such formulations are useful for treating symptoms of prion diseases as well as dysautonomias (e.g., familial dysautonomia, Parkinson's, Guillaine-Barre Syndrome, Aromatic-L-amino acid decarboxylase deficiency, tetrahydrobiopterin deficiency, familial paranganglioma syndrome; multiple system atrophy, dysautonomic symptoms associated with tumors such as pheochromocytoma, chemodectoma, and neuroblastoma; neurally mediated syncope, and SIDS) and pervasive development disorders such as autism, ADHD, ADD, and Asperger's.

(14) Patients below the age of 18 are typically given a dosage such that the formulation would deliver at least 5,000 USP units of protease and no more than 10,000 USP units of lipase per kilogram weight of patient, per day. Beneficially, the formulation would deliver at least 5,000 USP units of protease and no more than 7,500 USP units of lipase per kilogram weight of patient per day. Patients above the age of 18 are typically given no less than 5,000 USP units of protease per kilogram weight of patient per day.

(15) The dosage formulation may be administered by an oral preparation including, but not limited to, an encapsulated tablet, mini-tabs, microcapsule, mini-capsule, time released capsule, sprinkle or other methodology. In one embodiment, the oral preparation is encapsulated using lipid. Alternatively, the oral preparation may be encapsulated using enteric coating or organic polymers. A formulation may also be prepared using Prosolv technology, direct compression, dry granulation, wet granulation, and/or a combination of these methods.

(16) Fecal chymotrypsin level is a sensitive, specific measure of proteolytic activity, see e.g.: U.S. Pat. No. 6,660,831, incorporated by reference herein. Normal levels of chymotrypsin are considered be greater than 8.4 U/gram. Decreased values (less than 4.2 U/gram) suggest diminished pancreatic output (pancreatic insufficiency), hypoacidity of the stomach or cystic fibrosis. Elevated chymotrypsin values suggest rapid transit time, or less likely, a large output of chymotrypsin from the pancreas.

(17) For the fecal chymotrypsin test, a stool sample is collected from each of the subjects. Each stool sample can be analyzed using an enzymatic photo spectrometry analysis to determine the level of fecal chymotrypsin in the stool; in some cases the assay is performed at 30 C., see e.g.: U.S. Pat. No. 6,660,831, incorporated by reference herein. Alternatively, other methods, such as the colorimetric method, use of substrates, use of assays, and/or any other suitable method may be used to measure the fecal chymotrypsin levels. The levels of fecal chymotrypsin in the samples of the individuals having a prion disease are compared to the levels of fecal chymotrypsin in individuals not diagnosed with a prion disease determine if the individuals having the prion disease would benefit from the administration of digestive enzymes.

(18) The foregoing description of the embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of this disclosure. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.