Other

The General Hospital Corporation

Hybridon, Inc.

Worcester Foundation for Biomedical Research

Eliezer Rapaport

Paul C Zamecnik

David R Elmaleh

John W Babich

Valeri Metelev

Robert H Barker, Jr

A method for the treatment of atherosclerosis. The method includes the administration of a 32P-labeled agent as a beta emitter, such as 32P-labeled ATP or other 32P-labeled adenine nucleotides, whereby the 32P-labeled agent seeks and then permeates the atherosclerotic plaque en bloc without prior degradation. The accumulation of the 32P-labeled agent in the atherosclerotic plaque is achieved at time points whereby the 32P-labeled agent is cleared from the blood. Thus, radionuclide-labeled adenine nucleotides accumulate with high specificity in atherosclerotic lesions and in the heart. The beta particles (electrons) emitted by the 32P-label have a maximal path distance of about 0.5 cm and their energy preferentially destroy cells present in the atherosclerotic plaque without affecting vessel integrity or inducing arterial thrombosis.

Methods and compositions of [32P]-labeled adenine nucleotides for the treatment of atherosclerosis, vascular arterial diseases and coronary artery diseases

Adenine nucleotides such as adenosine 5'-monophosphate (AMP), adenosine 5&#x2032;-diphosphate (ADP) or adenosine 5&#x2032;-triphosphate (ATP) and/or adenosine and inorganic phosphate are administered in the treatment of advanced cancer in an out-patient setting and without serious side effects. Administration of up to 100 micrograms/kilogram/minute of continuous intravenous infusions of ATP for 8-10 hours, can be performed on an out-patient basis to patients who do not otherwise require hospitalization. No serious side effects, defined as grades 3 or 4 toxicity are observed during such an infusion.

Methods and therapeutic compositions in the treatment of advanced cancer

The administration of adenine nucleotides or adenosine and inorganic phosphate to a human host results in the generation of elevated liver, other organs and red blood cell adenosine 5'-triphosphate (ATP) pools as well as increased levels of ATP and adenosine in the extracellular blood plasma compartment of the blood. The present invention deals with the utilization of the elevated intracellular ATP levels and the elevated extracellular levels of ATP and adenosine for the treatment of a broad spectrum of clinical targets in HIV disease/AIDS and the achievement of decisive therapeutic gains.

Method of therapeautic treatments including human immunodeficiency virus (HIV) disease and other conditions in a human host by administering adenine nucleotides

The invention discloses methods for the chronic administration of adenosine, which contrary to the acute delivery of the drug by injection or infusion, acts in desensitizing adenosine receptors towards the action of adenosine. The methods and oral compositions of adenosine triphosphate (ATP), which is degraded to adenosine in vivo, can be used in the treatment of disorders and diseases that are therapeutically targeted by agonists or antagonists of adenosine receptors. One example is the stimulation of lipolysis in achieving weight loss in humans and in the treatment of obesity.

Methods, pharmaceutical and therapeutic compostions for administering adenosine

The present invention provides methods of resensitizing an anti-drug-resistant infectious agent to a drug. Also disclosed are synthetic oligonucleotides having a nucleotide sequence complementary to a region of pfmdr1 nucleic acid, and methods of down-regulating the expression of pfmdr nucleic acid using such oligonucleotides.

Oligonucleotide mediated reversal of drug resistance

The invention discloses methods and materials for the utilization of chemically modified oligonucleotides in the treatment of drug-resistant bacterial infections including drug-resistant tuberculosis.

Oligonucleotides active against drug-resistant bacteria

The invention provides cardiovascular imaging agents comprising a radionuclide in association with a nucleotide polyphosphate targeting molecule. Methods for using the cardiovascular imaging agents and kits containing the cardiovascular imaging agents or components suitable for production of the cardiovascular imaging agents are also provided.

Cardiovascular and thrombus imaging agents, methods and kits

The invention provides methods and materials for antisense oligonucleotide therapy against active pathogenic infection by drug resistant or drug sensitive pathogens, including Plasmodium falciparum.

Antiparasitic oligonucleotides active against drug resistant malaria

The administration of adenine nucleotides or adenosine and inorganic phosphate to a human patient results in the generation of elevated liver, other organs and red blood cell adenosine 5'-triphosphate (ATP) pools as well as increased levels of ATP in the extracellular blood plasma compartment of the blood. The present invention deals with the utilization of the elevated extracellular levels of ATP for achieving the well-established stimulation of insulin secretion following the interactions of extracellular ATP pools with pancreatic .beta. cell purine receptors. The invention is therefore concerned with the treatment of patients suffering from non-insulin-dependent diabetes mellitus (NIDDM or Type-II diabetes) and their chronic clinical complications which are the result of continuous hyperglycemia, by the administration of these physiological agents.

Method of treatment of diabetes mellitus by administration of adenosine 5'-

Administration of adenine nucleotides to a host is followed by their rapid degradation to adenosine and inorganic phosphate which promote increases in liver ATP pools. The turnover of expanded liver ATP pools supply the adenosine precursor for the subsequent expansions of red blood cell (total blood) and blood plasma (extracellular) ATP pools. Thus, the administration of AMP, ATP or their degradation products adenosine and inorganic phosphate to a host, achieve the beneficial increases in liver, total blood and blood plasma ATP levels.

Utilization of adenine nucleotides and/or adenosine and inorganic

Growth of tumor cells in a host is arrested by the generation of elevated blood and plasma levels of adenosine 5'-triphosphate in said host. These elevated levels can be achieved, for instance, by administering adenosine 5'-monophosphate, adenosine 5'-triphosphate, pharmaceutically acceptable salts thereof, or chelates thereof, or radio-nuclides thereof. Weight loss caused by cancer cachexia is substantially inhibited.

Anticancer activities in a host by increasing blood and plasma adenosine

A process by which the growth of malignant cells, e.g., human malignant cells, in a host is arrested and killed by treatment of the cells with low doses of adenosine 5'-diphosphate (ADP) or adenosine 5'-triphosphate (ATP), while normal cells thereof are substantially unaffected, is disclosed. ADP and ATP are capable of permeating through the plasma membrane of a variety of tumor cells, e.g., human tumor cells, and are incorporated into the cellular acid-soluble nucleotide pools of these cells, without prior breakdown to adenosine 5'-monophosphate (AMP) or adenosine, resulting in inhibition of DNA synthesis and cellular growth followed by cell death, while normal animal cells do not allow penetration of ADP or ATP through their plasma membrane without prior degradation.

Growing community of inventors

Belmont, MA, United States of America

Eliezer Rapaport