WO2001076606A2

WO2001076606A2 - Use of uric acid or precursors thereof as a treatment for cancer, aids and the like

Info

Publication number: WO2001076606A2
Application number: PCT/CA2001/000457
Authority: WO
Inventors: Roman Rozencwaig
Original assignee: Roman Rozencwaig
Priority date: 2000-04-07
Filing date: 2001-04-04
Publication date: 2001-10-18
Also published as: AU2001248173A1; WO2001076606A3; CA2304869A1

Abstract

Treatment or prevention of cancer, AIDS, infectious diseases, viral diseases, premature aging, depression, weakening of the immune system in a mammal by raising the level of uric acid in a person to about 300 to 500 νmol/l. Kit to monitor the levels of uric acid in a mammal requiring such treatment or liable to suffer from the above diseases is also disclosed.

Description

USE OF URIC ACID OR PRECURSORS THEREOF AS A TREATMENT FOR CANCER, AIDS AND THE LIKE TECHNICAL FIELD

The present invention relates to a method of medical treatment using uric acid or precursors thereof. More particularly, the invention is concerned with a method for the treatment of a patient suffering from cancer, AIDS, osteoporosis, an infectious disease, or a viral disease, premature aging, depression, or weakening of the immune system, using uric acid or precursors thereof. This treatment can also be used for preventing the occurrence of the above diseases or conditions in a person which is liable to suffer from them. BACKGROUND ART

A living organism has a defense system to fight cancer formation, cancerous tumors and metastatic lesions through the entire organism. This system is genetically programmed and is affected by environmental factors such as nutrition, medications and neutroceuticals , etc. One third of all individuals in the U.S.A. will develop cancer. Cancer is a second cause of death in the U.S.A. Half of the deaths are from three of the most common types of cancer: lung, breast and colon rectum. On the other hand, the occurrence of malignancy in deaths in patients with gout is only 11% as compared with 33% in non gouty patients (or general population). It was observed that patients with gout and/or patients with high normal levels (350 to 450 μmol/1 or uric acid) without gout have substantially less or no cancer, significantly lower incidence of infections, live longer and appear much healthier than patients whose uric acid is 300 μmol/1 or less.

At the same time it was observed that patients with cancer (other than leukemia) had either low serum uric acid or below normal (between 140 and 230 μmol/1. A subsequent analysis of the data relative to the levels of uric acid was made in 10 patients with AIDS. It was found out that in 7 out of 10 patients the levels of uric acid were between 140 - 220 μmol/ and that 3 out of 10 patients had levels of uric acid between 350 - 450 μmol/1. The three patients whose uric acid was 350 - 450 μmol/1 were doing extremely well and had no overt signs of AIDS.

It is also known that people with high uric acid levels are more prone to developing hypertension, heart disease (A.S.H.D.), kidney stones and diabetes. However, this group can easily be treated with standard therapies, which are available in the year 2000. These treatments can consist of diet manipulation, lipid lowering drugs, antithrombotic drugs such as Aspirin^® or other antiplatelet medication. In addition, hypertension can easily be treated with antihypertensive medications.

However, a large number of people with uric acid levels of 350 - 450 μmol/1 do not develop these problems. If gout does occur, it can also be treated with drugs that lower uric acid, and anti-inflammatory medications. These observations have been confirmed in a survey where the incidence of neoplasms in families of patients with high levels of uric acid was studied. It was found that the incidence of cancer in parents and grand-parents of people with high uric acid was 9.2% as compared with 80% in those whose uric acid was between 160 - 250 μmol/1 (which is the lower range of normal). It was also observed that people with high levels of uric acid for example in the range of 350 - 450 μmol 1 are less susceptible of catching viral or infectious diseases, of prematurely aging, of undergoing depression, of suffering from fibromyalgia, or a weakening of their immune system, than those with low normal levels of uric acid. A hypothesis was even made in the prior art to the effect that uric acid may provide an antioxidant defense in humans against cancer (PNAS USA), 1 78: 6858 - 6862 (1981). However, it was not established in this reference, how to treat people against cancer using uric acid and the hypothesis was never confirmed. There is also a suggestion in the prior art to combine uric acid with a lymphokine or a cytotoxin, or with a tumor necrosis factor, or a colony stimulating factor to treat damage to cells, tissue or other body parts in a mammalian host (U.S. 5,508,031; 5,667,776 and 5,702,697). The presence of uric acid is merely intended at protecting the person treated against damage caused by the therapeutic agent, and is not aimed at curing cancer. U.S. 3,105,009 discloses using maleuric acid to inhibit mitosis of tumor cells. It should be noted that maleuric acid is a substantially different compound than uric acid. Furthermore, this Patent teaches a direct contact of the tumor cells with maleuric acid, contrary to what is proposed in the present invention. U.S. 5,872,124 teaches using uric acid for treating a disease of the central nervous system, which may include AIDS. No indication is given of how to specifically use uric acid to achieve the desired result, except to propose an effective dose of uric acid. This Patent discloses a treatment for neurological damage. More specifically, the Patent suggests to treat allergic encephalitis which may occur in AIDS, however, it does not suggests treating AIDS per se.

U.S. 6,028,076 discloses the use of specific purine derivatives which do not include uric acid to treat diseases against which interferon is effective. This Patent deals with the treatment of random diseases, it does not teach a treatment for a specific disease. DISCLOSURE OF INVENTION

It is an object of the present invention to provide a treatment for mammals suffering from cancer, AIDS, osteoporosis, an infectious disease, or a viral disease using uric acid or precursors thereof. It is another object of the present invention to provide a prevention treatment whereby mammals susceptible of catching diseases such as cancer, AIDS, osteoporosis, an infectious disease or a viral disease are treated with uric acid or a precursor thereof.

It is another object of the present invention to provide a treatment for preventing mammals from premature aging, depression, fibromyalgia, or undergoing a weakening of their immune system, by treating them with uric acid or a precursor thereof.

The present invention relates to the use of uric acid or a precursor thereof, there is provided a method for the treatment of a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease, a viral disease, premature aging, depression, a weakening of the immune system, or for preventing the occuπence of same in a mammal liable to suffer from same, until the level of serum uric acid in the mammal is raised to about 300 to about 450 μmole/1. The precursor of uric acid, which is preferred, is a nucleic acid, which comprises ribonucleic acid, deoxyribonucleic acid and brewer's yeast.

Uric acid or its precursor may be administered orally or intravenously. In the case of uric acid, the preferred dose would be one ^■ which would increase the serum uric acid concentration to be between, about 300 and 450 μmol/1. In the case of a precursor of uric acid, the preferred dose is between about 400 and 800 mg.

The invention also relates to the Use of uric acid or a precursor thereof for the preparation of a medicament for the treatment of a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease or a viral disease, premature aging, depression, weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, until the level of serum uric acid in said mammal is raised to about 300 to 450 μmol/1. The invention also relates to a kit for the determination of levels of uric acid in a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease, a viral disease, premature aging, depression, and weakening of the immune system or liable to suffer from same, said kit including a uric acid indicator capable of determining serum uric acid in a mammal within the range of about 100 to about 450 μmol/1. MODES OF CARRYING OUT THE INVENTION

The invention is now illustrated by means of the following test cases, all dealing with some forms of cancer. However, since mammals with high levels of uric acid do not generally suffer from other related diseases as mentioned above, it is reasonable to assume that the above treatment with uric acid or a precursor of uric acid, may apply to the other related diseases. Test case 1

The patient was a 52-year-old Caucasian female who had breast cancer diagnosed in 1984. The same year, she had mastectomy and was found PGR positive. She was subsequently treated with chemotherapy and Tamoxifen. In 1997, she had metastatic pleural effusions and was treated with Epirubicin and Taxol. In spite of treatments, her disease increased and she was treated with Xelodex. Nevertheless, the patient continued to deteriorate. In January 2000, her uric acid level was 186 μmol/1 and in addition to her regiment she was started on high purine diet and uric acid precursors (RNA + DNA = brewer's yeast 1000 mg). One month later, her uric acid improved to 224 μmol/1 and her weight increased by 3 pounds. She also feels better and the progression of cancer appears to be clinically aπested. Test case 2

The patient is a 46 year old Caucasian female. She was diagnosed with advanced cervix cancer. She was treated with combined chemo/radiation protocol. She was improved but still complained of fatigue and lymphadenopathy in the inguinal area. Her uric acid has been fluctuating between 132 μmol/1 to 178 μmol/1. She was put on high purine diet plus precursor of uric acid (RNA + DNA + brewer's yeast - 500 tid). Six weeks later, the lymph nodes in the inguinal area are not palpable while her uric acid increased to 282 μmol/1. Presently she feels stronger than she has been for 6 years. She is being followed regularly. Test case 3

This patient is a 73 -year-old Caucasian . male who presented a prostate carcinoma, which metastasized to lymph nodes. Upon examination he had a 6-cm lymph node in the Lt. inguinal area and his PSA was 58 which increased recently from 17. Uric acid was

208 μmol/I. He was taking Zolodex 1 tab t.i.d. A supplement of nucleic acids was added at dose of 500 mg, three times a day. Two weeks later, the lesion in groin decreased to 2 cm and uric acid increased to 240 μmol/1.

One month later, the lesion in the inguinal area was undetectable. His P.S.A. decreased to 21 and uric acid increased to 276 μmol/le. He feels stronger, able to cope well and is less anxious.

Test case 4

The patient is a 78-year-old man with rectal polyps. The bleeding per rectum occurred during the last 6 months and the patient had colonoscopy to determine if the bleeding was secondary to neoplasm. The biopsy revealed colonic neoplasm and the patient is scheduled for surgical resection. His uric acid was found to be 204 μmol/1. He was placed on a high purine diet and precursors of uric acid (RNA+ DNA + brewer's yeast)

500 mg t.i.d., while awaiting surgery. Two weeks later, the serum uric acid went up to 284 and bleeding per rectum stopped. The patient will undergo another colonoscopy and biopsy, but is presently reasonably well.

Test case 5

The patient is a 58-year-old Caucasian female who was diagnosed in

1997 with ovarian cancer, involving entire peritoneum. She had total abdominal hysterectomy, bilateral salpingo - oophorectomy, infracolic omentectomy, transverse colectomy and a biopsy of retrosigmoid nodule. The pathological report was as follows: lymph nodes - metastatic carcinoma of myometrium, ovaries showed pooly differentiated papillary serous adenocarcinoma. After surgery, the patient improved but in 1999, she developed metastasis to the cerebellum. In 1999, cerebellar metastasis was removed surgically. Upon reviewing the case, it was noted that the serum uric acid levels were low normal: in 1997 it was 188 μmol/1 and in 1999 uric acid was 182 μmol/1. In February 2000, she was started on high purine diet and uric acid precursors (RNA, DNA, Brewer's yeast, 500-mg t.i.d.). Six weeks later her serum uric acid rose to 264 μmol/1 and she feels well. There is no evidence or recurrences. The patient is being monitored closely.

• To summarize, people with uric acid levels above about 350 μmol/1 appear younger, healthier, usually free of cancer and free of upper respiratory infections. It was also observed that patients with gout or high uric acid experienced very few infections, days missed at work due to infections. As a result of these findings it is believed that monitoring serum uric acid levels and using either uric acid per se or precursors thereof such as nucleic acids to elevate serum uric acid to levels between 350 - 450 μmol/1 is beneficial in treatment and prevention of cancers, infections, AIDS, osteoporosis, and other related diseases. Therefore, according to the present invention, uric acid may be used as for example an antibiotic, an antiviral, an anti-cancer agent. Also uric acid can be used in prevention of cancer in patients with low uric acid levels and a high risk factor for cancer. Uric acid can also be used in prevention of frequent infections such as upper respiratory infections, AIDS and viral infections and also depression.

Of course, it is within the scope of the present invention to use the above treatment for other disease than cancer such as those mentioned above, and to provide a kit for the determination of levels of uric acid in a mammal requiring such treatment or liable to suffer from the above diseases.

Claims

1. Use of uric acid or a precursor thereof for the treatment of a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease or a viral disease, premature aging, depression, weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, until the level of serum uric acid in said mammal is raised to about 300 to 450 μmol/1.

2. Use according to claim 1, wherein uric acid is used.

3. Use according to claim 1, wherein a precursor of uric acid is used.

4. Use according to claim 3, wherein said precursor of uric acid is a nucleic acid comprising ribonucleic acid, deoxyribonucleic acid and brewer's yeast.

5. Use according to claim 1, wherein said uric acid or precursor thereof is conditioned for oral administration.

6. Use according to claim 1, wherein said uric acid or precursor thereof is conditioned for intravenous administration.

7. Use according to claim 3, at doses of between 400 and 800 mg.

8. Use of uric acid or a precursor thereof for the preparation of a medicament for the treatment of a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease or a viral disease, premature aging, depression, weakening of the immune system, or for preventing the occurrence of same in a mammal liable to suffer from same, until the level of serum uric acid in said mammal is raised to about 300 to 450 μmol/1.

9. Use according to claim 8, wherein said medicament comprises uric acid.

10. Use according to claim 8, wherein said medicament comprises a precursor of uric acid.

11. Use according to claim 10, wherein said precursor of uric acid is a nucleic acid comprising ribonucleic acid, deoxyribonucleic acid and brewer's yeast.

12. Use according to claim 8, wherein said uric acid or precursor thereof is conditioned for oral administration.

13. Use according to claim 8, wherein said uric acid or precursor thereof is conditioned for intravenous administration

14. Use according to claim 10. wherein said medicament comprises doses of between 400 and 800 mg.

15. Kit for the determination of levels of uric acid in a mammal suffering from cancer, AIDS, osteoporosis, an infectious disease, a viral disease, premature aging, depression, and weakening of the immune system or liable to suffer from same, said kit including a uric acid indicator capable of determining serum uric acid in a mammal within the range of about 100 to about 450 μmol/1.