SP-SAP as Chronic Pain Therapeutic

ADVANCED TARGETING SYSTEMS ANNOUNCES ITS MOLECULAR NEUROSURGERY TECHNOLOGY OPENS DOOR TO PERMANENT RELIEF FOR CHRONIC PAIN

SAN DIEGO, CA, NOVEMBER 18, 1999— Chronic, intractable pain afflicts millions of Americans. Pioneering new technology, called molecular neurosurgery and developed by Advanced Targeting Systems, a San Diego-based company, provides the springboard for a one-time injection of a targeted toxin that could result in permanent relief for those suffering constant, unrelenting and crippling pain from cancer and other illnesses. These results are reported in the November 19 issue of the journal Science.

The targeted toxin used in the pain studies is a chemical conjugate composed of the neuropeptide Substance P, and the ribosome-inactivating protein saporin. According to Douglas Lappi, Ph.D., President and Senior Scientist of Advanced Targeting Systems, “Substance P-saporin targets delivery of a toxic compound to those nerve cells that transmit pain messages up the spinal cord to the brain. This precise method allows chronic pain to be permanently stopped without affecting normal pain transmission.”

FIGURE LEGEND:
PROGRAMMED DEATH:
Substance P-Saporin targets delivery of a toxic compound to eliminate those nerve cells that transmit pain messages (yellow highlight) up the spinal cord to the brain.
This precise method allows chronic pain to be permanently stopped without affecting other neurons (red).
This technology created by San Diego-based Advanced Targeting Systems, creates the spring board for providing a one-time injection of a targeted toxin that could result in permanent relief for those suffering constant pain from cancer and other illnesses.

Dr. Lappi, the inventor of numerous agents and an innovator in the development of targeted toxins, explains, “The scalpel in molecular neurosurgery is saporin, a protein from the seeds of the plant, Saponaria officinalis. Saporin has no way of entering a cell on its own, but when attached to a targeting agent such as an antibody or neuropeptide, it is directed inside the cell and causes cell death. In the case of Substance P-saporin, the saporin is internalized along with Substance P and eliminates those neurons while leaving bystander neurons untouched.”

Dr. Lappi, author of more than 70 scientific publications, devised the idea of studying pain pathways by using the Substance P receptors as a gateway to get inside the target neurons.

Lappi contacted noted University of Minnesota pain expert Dr. Patrick Mantyh to use the material. The current report in Science covers work completed in Mantyh’s laboratory. Mantyh, a pioneer in the use of the molecule in chronic pain research and treatment, first reported on initial results from the use of Substance P-Saporin in a 1997 Science issue.

The targeted toxin on which the research is based centers around an idea first proposed by Ronald G. Wiley, M.D., Ph.D., scientific advisor to Advanced Targeting Systems and clinical neurologist at the Veteran’s Administration Medical Center, Nashville, TN. Advanced Targeting Systems has patents pending for Substance P-Saporin and its uses.

According to the published research in Science, the Substance P-saporin is working well in the laboratory and, according to Lappi, “This means limited clinical trials in humans could begin within two years.”

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