From the European Patent Office
Treatment of spinal cord injury with a Poxvirus-encoded complement inhibiting protein such as vaccinia virus complement control protein
Cross-Reference to Related Applications
This application claims priority under 35 U. S. C.119 (e) of U. S. Application
Number 60/500, 667, filed September 5,2003.
Technical Field
The present invention relates to the treatment of spinal cord injury with a Poxvirus-encoded complement inhibiting protein such as vaccinia virus complement control protein (VCP).
Background
Every year in the United States, more than 10,000 people experience spinal cord injury (SCI), with an estimated 250,000 of those cases sufficiently severe to require wheelchair use. A majority of SCI patients are injured while under the age of 30 years and will often experience a normal lifespan, leading to extremely high medical costs over the course of a lifetime.
SCI is an extremely difficult condition to understand and manage in a clinical setting due to the multitude of injury mechanisms involved. In addition to the primary injury, it is thought that a complex array of secondary injury mechanisms account for the progression of damage from the central gray matter to the surrounding white matter that begins within minutes and persists long after primary injury. After several days to weeks, the initial injury can expand in size, leading to a scar-encapsulated cavity many times the size of the original lesion. The cavity is bounded by abnormally proliferating glial cells and primarily astrocytes, which can form a physical barrier to any potential neuronal regeneration. Suspected secondary injury mechanisms include hemorrhage, ischemia- reperfusion, excito-toxicity, demyelination, calcium mediated injury, disturbances in mitochondrial function, apoptosisand/or necrosis of neurons andoligodendrocytes, and inflammation.
Currently, only one therapeutic agent, methylprednisolone (MP), is widely considered standard therapy after traumatic SCI. MP is a synthetic glucocorticosteroid that has been subjected to several large-scale human clinical trials and showed minor clinical benefits when administered within 48 hours of SCI. However, questions regarding MP's efficacy persist due to controversy surrounding study design and analysis/interpretation of data from clinical trials. Therefore, continued investigation and evaluation of potential therapeutic agents for traumatic SCI is paramount. Accordingly, there is a need for methods to treat SCI.
Summary of the Invention
In one aspect, the invention provides for methods of treating a patient having a spinal cord injury. Such methods include administering to the patient an effective amountof Poxvirus-encoded complement inhibiting protein and a pharmaceutically-acceptable carrier. Typically, the effective amount of the Poxvirus-encoded complement inhibiting protein treats at least one symptom associated with the spinal cord injury. As used herein, "treating"refers to ameliorating at least one symptom of a rheumatic disease, or curing and/or preventing the development of a rheumatic disease or condition.
In certain embodiments, administration of the Poxvirus-encoded complement inhibiting protein delaysand/or prevents the onset of at least one symptom of the spinal cord injury. In other embodiments, administration of Poxvirus-encoded complement inhibiting protein reduces spinal cord damage associated with the spinal cord injury, reduces inflammation associated with the spinal cord injury,and/or reduces loss of motor function associated with the spinal cord injury.
In some embodiments, thePoxvirus-encoded complement inhibiting protein isVCP (e. g. , recombinant VCP), IMP, smallpox complement inhibiting protein, monkeypox complement inhibiting protein, or variola virus complement inhibiting protein.
In some embodiments, the Poxvirus-encoded complement inhibiting protein can be administered intraperitoneally.Ill other embodiments, the Poxvirus-encoded complement inhibiting protein can be administered into the spinal cord area. In addition, the Poxvirus-encoded complement inhibiting protein can be administered in multiple administrations. The Poxvirus-encoded complement inhibiting protein also can be administered in combination with at least one additional agent such as a nonsteroidal anti- inflammatory drug(NSAID), or a corticosteroid.
In another aspect, the invention provides for methods of treating a patient having a spinal cord injury. Such methods include administering to the patient an effective amount of Poxvirus-encoded complement inhibiting protein and a pharmaceutically-acceptable carrier, wherein the Poxvirus-encoded complement inhibiting protein is selected from the group consistingof VCP, IMP, monkeypox complement inhibiting protein, smallpox complement inhibiting protein, and variola virus complement inhibiting protein.
Typically, the effective amount of the Poxvirus-encoded complement inhibiting protein treats at least one symptom associated with the spinal cord injury.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the drawings and detailed description, and from the claims.