METHOD FOR DIAGNOSING AND TREATING DYSAUTONOMIA AND OTHER DYSAUTONOMIC CONDITIONS

Abstract

A method for treating a Parkinson's patient with digestive/pancreatic enzymes involves administering an effective amount of digestive/pancreatic enzymes to an individual having the disorder in order to improve a symptom of the disorder. In addition, a method is provided for determining whether an individual has, or may develop, Parkinson's disease or related dysautonomic disorders and for determining whether an individual will benefit from the administration of pancreatic/digestive enzymes to treat the dysautonomic disorder.

Claims

1. A pharmaceutical preparation to treat a dysautonomic disorder in an individual comprising a therapeutically effective amount of digestive enzymes.

2. The pharmaceutical preparation of claim 1, wherein the dysautonomic disorder is Parkinson's disease.

3. The pharmaceutical preparation of claim 1, wherein the digestive enzyme is selected from the group consisting of: amylase, lipase, protease, and a combination thereof.

4. The pharmaceutical preparation of claim 1, wherein the digestive enzyme is further selected from the group consisting of: chymotrypsin, trypsin, pancreatin, papaya, papain, and a combination thereof.

5. The pharmaceutical preparation of claim 1, wherein the enzymes are derived from a source selected from the group consisting of animal enzymes, plant enzymes, synthetic enzymes, and a combination thereof.

6. The pharmaceutical preparation of claim 1 wherein the preparation is manufactured using a technology selected from the group consisting of PROSOLV technology, enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and a combination thereof.

7. The pharmaceutical preparation of claim 1, wherein the preparation is administered orally via a dosage formulation selected from the group consisting of pills, tablets, capsules, microcapsules, mini-capsules, time-released capsules, mini-tabs, sprinkles, and a combination thereof.

8. The pharmaceutical preparation of claim 3, wherein the amount of amylase ranges from 10,000 to 70,000 U.S. Pharmacopeia (U.S.P.) units/mg.

9. The pharmaceutical preparation of claim 3, wherein the amount of protease ranges from 10,000 to 80,000 U.S.P. units/mg.

10. The pharmaceutical preparation of claim 3, wherein the amount of lipase ranges from 4,000 to 80,000 USP units/mg.

11. The pharmaceutical preparation of claim 4, wherein the amount of pancreatin ranges from 2,000 to 6,000 U.S.P. units/mg.

12. The pharmaceutical preparation of claim 4, wherein the amount of chymotrypsin ranges from 2 to 7 mg.

13. The pharmaceutical preparation of claim 4, wherein the amount of papain ranges from 3,000 to 30,000 U.S.P. units/mg.

14. The pharmaceutical preparation of claim 4, wherein the amount of papaya ranges from 30 to 500 mg.

15. The pharmaceutical preparation of claim 4, wherein the amount of trypsin ranges from 60 to 100 mg.

16. The pharmaceutical preparation of claim 1, wherein a symptom of the dysautonomic disorder is ameliorated.

17. The pharmaceutical preparation of claim 1 wherein the symptom of the dysautonomic disorder is selected from the group consisting of constipation, tremors, falls, difficulty in ambulation, and a combination thereof.

18. A method of treating an individual having a dysautonomic disorder with a therapeutically effective amount of digestive enzymes comprising the steps of: measuring a level of fecal chymotrypsin in a stool sample of the individual; comparing the level of fecal chymotrypsin with a normal fecal chymotrypsin level; and administering the digestive enzymes to the individual if the level of fecal chymotrypsin in the individual is less than the normal fecal chymotrypsin level.

19. The method of claim 18, further comprising the steps of: administering the digestive enzymes to the individual in order to promote protein digestion; and administering the digestive enzymes to the individual in order to ameliorate a symptom of the dysautonomic disorder.

20. The method of claim 18, wherein the stool sample is measured using a technique selected from the group consisting of enzymatic photospectrometry, colorimetry, treatment with substrates, assays, and a combination thereof.

21. The method of claim 18, wherein the normal fecal chymotrypsin level is approximately 8.4 U/gram.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIG. 1 is a graph demonstrating the decrease in occurrences of constipation in Parkinson's patients after administration of digestive enzymes over a period of 180 days.

[0031] FIG. 2 is a graph demonstrating the increase in the number of bowel movements in Parkinson's patients after administration of digestive enzymes over a period of 180 days.

[0032] FIG. 3 is a graph demonstrating the decrease in occurrences of tremors in Parkinson's patients after administration of digestive enzymes over a period of 180 days.

[0033] FIG. 4 is a graph demonstrating the decrease in occurrences of falls in Parkinson's patients after administration of digestive enzymes over a period of 180 days.

[0034] FIG. 5 is a graph demonstrating the changes in ambulation in Parkinson's patients after administration of digestive enzymes over a period of 180 days.

[0035] FIG. 6 is a graph demonstrating the difference in the fecal chymotrypsin levels of Parkinson's and non-Parkinson's subjects.

DETAILED DESCRIPTION

[0036] The present invention is directed to methods for aiding in the diagnosis of dysautonomic disorders and dysautonomic conditions, and for treating individuals diagnosed as having a dysautonomic disorder and other disorders having dysautonomic components. In one embodiment, a method is provided for determining the presence of abnormal protein digestion and/or pancreatic dysfunction of an individual, especially a child, by analyzing a stool sample of the individual for the quantitative levels of one or more pancreatic enzymes including, but not limited to, chymotrypsin, so as to determine if the individual has, or may develop, a dysautonomic disorder or condition. In another embodiment, a method is provided for determining whether the individual is likely to benefit from the administration of secretin, CCK, VIP, digestive enzymes, other peptides, and/or neuropeptides. Until now, there has been no clear biological marker for dysautonomic disorders or conditions to allow early diagnosis or screening of such disorders or conditions.

[0037] It has been discovered by the inventor herein that a population of individuals suffering from dysautonomic disorders such as Parkinson's disease have abnormal or pathologic levels of pancreatic enzymes such as chymotrypsin in their stools. It is postulated that in dysautonomic syndromes, the partial paresis of the gastrointestinal tract, and therefore the lack of functioning of the secretory cells of the proximal small intestine, preclude the proper formation and/or release of secretin. It is further postulated that this abnormal protein digestion, as reflected by the low levels of pancreatic enzymes such as chymotrypsin, can be improved by the administration of secretin, CCK, VIP, other neuropeptides, peptides, and/or digestive enzymes to thereby ameliorate the symptoms of dysautonomic conditions. Indeed, as a low measure of fecal chymotrypsin, for example, expresses an abnormality of protein digestion and/or pancreatic dysfunction, it is postulated that an improvement of protein digestion to promote normal growth and development of an individual suffering from a dysautonomic disorder or dysautonomic condition by the administration of secretin, CCK, VIP, other neuropeptides and/or peptides and/or digestive enzymes, can ameliorate the dysautonomic symptoms.

[0038] In one embodiment, a stable preparation of digestive/pancreatic enzymes is formed into a dosage formulation containing a therapeutically effective amount of a protease, an amylase, and/or a lipase. The formulation may include additional enzymes, such as pancreatin, chymotrypsin, trypsin, papain and/or papaya. 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 PROSOLV technology. Alternatively, the oral preparation may be encapsulated using enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and/or a combination of these methods.

[0039] The dosage formulations may be as follows (U.S.P.=U.S. Pharmacopeia):

Example 1

[0040]

TABLE-US-00001 Amylase 10,000-70,000 U.S.P. units/dose Protease 10,000-80,000 U.S.P. units/dose Lipase 4,000-40,000 U.S.P. units/dose Pancreatin 2,000-6,000 U.S.P. units/dose Chymotrypsin 2-5 mg Trypsin 60-100 mg Papain 3,000-30,000 U.S.P. units/dose Papaya 30-500 mg

Example 2

[0041]

TABLE-US-00002 Protease 40,000 U.S.P. units/dose Chymotrypsin 2-7 mg Trypsin 60-100 mg Papaya 30-500 mg

Example 3

[0042]

TABLE-US-00003 Amylase 30,000 U.S.P. units/dose Protease 40,000 U.S.P. units/dose Lipase 30,000 U.S.P. units/dose Chymotrypsin 2-7 mg Papaya 30-500 mg

Example 4

[0043]

TABLE-US-00004 Amylase 30,000 U.S.P. units/dose Protease 40,000-80,000 U.S.P. units/dose Lipase 30,000-80,000 U.S.P. units/dose Chymotrypsin 2 mg Papain 6,000-30,000 U.S.P. units/dose

[0044] Other combinations of digestive enzymes may also be used. These enzymes can be in the form of animal or plant derivatives, natural or synthetic.

[0045] In a study conducted by the inventor, sixteen subjects diagnosed with Parkinson's disease and ranging in age from 41 to 71 were examined were examined. Physical symptoms of the disease, such as constipation, lack of bowel movements, tremors, falling, and an inability to walk were monitored and measured over a period of 180 days. The subjects were given a dosage of digestive enzymes 3-5 per day. The dosages were administered in the form of encapsulated tablets, capsules, and sprinkles. The dosages were taken with meals and snacks. The digestive enzyme dosage included, but was not limited to, one or more of the following: amylases, proteases, pancreatin, papain, papaya, lipases, chymotrypsin, and trypsin.

[0046] Ninety-five percent of adults have bowel movements between three and 21 times per week, and this would be considered normal. The most common pattern is one bowel movement a day. However, some people do not have bowel movements every day or the same number of bowel movements each day. Medically speaking, constipation usually is defined as fewer than three bowel movements per week. Severe constipation is defined as less than one bowel movement per week.

[0047] Referring to FIG. 1, a majority of the subjects experienced moderate to severe constipation prior to any treatment with digestive enzymes. The severity of the constipation was measured on a scale of 1 to 7, with 1 equaling no constipation and 7 equaling severe constipation. The subjects were monitored at 30, 90, 120 and 180 day intervals. Over the course of the 180 day treatment, the severity of the constipation decreased from severe to moderate to mild in the majority of the subjects.

[0048] Referring to FIG. 2, the number of bowel movements per week experienced by most of the subjects was lower than normal prior to any treatment with digestive enzymes. The subjects were monitored at 30, 90, 120 and 180 day intervals. Over the course of the 180 day treatment, the number of bowel movements per week increased to 3 or more in the majority of subjects.

[0049] Static tremors, or resting tremors, are tremors that occur despite the limb being fully supported and at rest against gravity. They usually progress at the rate of 4-7 Hz (hertz), and are the typical Parkinsonian tremor. The amplitude of the tremor often decreases with sleep, complete relaxation or voluntary activity. Tremors are often the first symptom that people with Parkinson's disease or their family members notice. Initially, the tremors may appear in just one limb (arm or leg) or only on one side of the body. The tremors also may affect the lips, tongue, neck, or eyelids. As the disease progresses, the tremors may spread to both sides of the body, although in some cases the tremors remain on just one side. Emotional and physical stress tend to make the tremors worse.

[0050] Referring to FIG. 3, a majority of the subjects experienced severe tremors prior to any treatment with digestive enzymes. The severity of the tremors was measured on a scale of 1 to 7, with 1 equaling no tremors and 7 equaling severe tremors. The subjects were monitored at 30, 90, 120 and 180 day intervals. Over the course of the 180 day treatment, the severity of the tremors decreased from severe to moderate to mild in a majority of the subjects.

[0051] Many Parkinson's patients develop gait and balance problems and this can lead to falls. Ambulation is with a stooped posture using a short, shuffling gait. This is primarily due to the loss of balance control. Unfortunately with Parkinson's disease, the muscles become stiff and patients have difficulty swinging their arms when walking which helps in keeping one's balance. They also have episodes of freezing which literally have them stuck in place when initiating a step and they exhibit a slight foot drag which makes tripping easy. Persons with Parkinson's have difficulty in judging spatial relationships. Thus, falls often happen when navigating through doorways or through narrow passages.

[0052] Referring to FIG. 4, a majority of the subjects experienced an elevated number of falls prior to any treatment with digestive enzymes. The subjects were monitored at 30, 90, 120 and 180 days. Over the course of the 180 day treatment, the number of falls decreased to less than two per week in a majority of the subjects.

[0053] Referring to FIG. 5, a majority of the subjects experienced severe difficulty in ambulation prior to any treatment with digestive enzymes. The difficulty in ambulation was measured on a scale of 1 to 7, with 1 equaling no difficulty and 7 equaling severe difficulty. The subjects were monitored at 30, 90, 120 and 180 day intervals. Over the course of the 180 day treatment, the difficulty in ambulation decreased from severe to moderate to some or no difficulty in a majority of the subjects.

[0054] Fecal chymotrypsin levels were also measured in the 16 subjects and compared to the fecal chymotrypsin levels of 16 subjects who did not have Parkinson's disease. The non-Parkinson's subjects ranged in age from 44 to 77. Fecal chymotrypsin is a sensitive, specific measure of proteolytic activity. 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.

[0055] A stool sample was collected from each of the subjects. Each stool sample was analyzed using an enzymatic photospectrometry analysis to determine the level of fecal chymotrypsin in the stool. 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 Parkinson's patients were compared to the levels of fecal chymotrypsin in the non-Parkinson's subjects to determine if the Parkinson's patients would benefit from the administration of digestive enzymes.

[0056] Referring to FIG. 6, the fecal chymotrypsin levels of the Parkinson's patients ranged from 0.8 to 6.6 U/gram, with a mean of 2.84 U/gram, while the fecal chymotrypsin levels of the non-Parkinson's patients ranged from 9.2. to 47.4 U/gram, with a mean of 28 U/gram. Thus, it can be seen that the fecal chymotrypsin levels of the Parkinson's patients were markedly decreased when compared to the non-Parkinson's subjects.

[0057] In summary, the results of the study described herein demonstrate that administration of digestive enzymes benefits individuals having a dysautonomic disorder, such as Parkinson's disease, by ameliorating the symptoms of the disorder. Furthermore, the results of the study indicate that measurement of the fecal chymotrypsin level in individuals having a dysautonomic disorder can determine if the individual will benefit from the administration of digestive enzymes.

[0058] 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.