The present invention relates to a method for preventing and/or treating hyperlipemia and its related conditions in a subject, comprising administering a prophylactically and/or therapeutically effective amount of plasminogen to the subject susceptible to hyperlipemia, suffers from hyperlipemia or other diseases accompanied by hyperlipemia. The present invention further relates to a medicament, a pharmaceutical composition, an article of manufacture, and a kit comprising plasminogen which are useful for preventing and/or treating hyperlipemia and its related conditions in a subject.

Disclosed is a method for treating amyotrophic lateral sclerosis (ALS), including administering a therapeutically effective amount of a plasminogen pathway activator to a subject. Further disclosed are a pharmaceutical composition, a product, and a kit comprising the plasminogen pathway activator, for treating amyotrophic lateral sclerosis.

Subjects of the invention are a method of plasminogen supplementation in a plasminogen-deficient subject, and method for the treatment of plasminogen-deficiency in a plasminogen-deficient subject. These methods comprise administering to the plasminogen-deficient subject a dose of plasminogen, and more particularly Glu-plasminogen, for increasing the subject plasminogen activity level by at least about 1%, and more particularly by at least 10%, of the normal plasminogen activity and for maintaining the plasminogen activity level over a supplementation period or a treatment period. The plasminogen-deficient subject of the present invention may suffer from Type-I, Type-II plasminogen-deficiency or an acquired deficiency.

The present invention discloses modified forms of plasmin with advantageous properties. As compared to their natural unmodified form, these variants exhibit significantly modulated kinetics in terms of delayed inhibition characteristics in the presence of specific inhibitors, such as α.sub.2-antiplasmin (α.sub.2-AP). These include PEG-conjugated thiol derivatives of truncated plasmin with potential clinical applications in various regimens of thrombolytic therapies.

The present invention relates to plasminogen for use in a method for preventing or treating a thrombotic event in a patient, wherein the patient is at risk of developing or is suffering from microthrombi.

The present invention concerns the use of plasminogen, a variant thereof, or an analog thereof having a plasminogen activity, for the prevention or treatment of a condition or a disease that is characterized with an increased PAI-1 level. The conditions and diseases that are characterized with an increased PAI-1 level, are regrouped within two categories: the diseases associated with an impaired vascular or tissue remodeling capacity, and the metabolic and hormonal disorders associated with an increased PAI-1 level.

Provided are methods for producing biologically active mutant recombinant plasminogen polypeptides with desired pharmaceutical properties. The refolded polypeptides may be treated with a plasminogen activator, such as tPA, urokinase, or streptokinase to generate biologically active mutant plasmin polypeptide for pharmaceutical use. Methods are also provided to producing biologically active fusion recombinant mutant plasminogen/plasmin polypeptides that can cross the BBB through receptor mediated transcytosis. The fusion partner may carry the mutant plasminogen/plasmin polypeptides into the brain for increased therapeutic efficiency.

A system for the physical manipulation of free magnetic rotors in a circulatory system using a remotely placed magnetic field-generating stator is provided. In one embodiment, the invention relates to the control of magnetic particles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow. Examples of vascular occlusions targeted by the system include, but are not limited to, atherosclerotic plaques, including fibrous caps, fatty buildup, coronary occlusions, arterial stenosis, restenosis, vein thrombi, arterial thrombi, cerebral thrombi, embolisms, hemorrhages, other blood clots, and very small vessels.

Some embodiments provide a system for external manipulation of magnetic nanoparticles in vasculature using a remotely placed magnetic field-generating stator. In one aspect, the systems and methods relate to the control of magnetic nanoparticles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow.

The present invention relates to a method and a drug for preventing or treating osteoarthritis by plasminogen. Specifically, the present invention involves administering an effective amount of plasminogen to an osteoarthritis subject for treating the osteoarthritis. In addition, the present invention further relates to an osteoarthritis treatment drug comprising plasminogen, a product, and a kit.