Patient Eligibility Criteria | |
Age | Between 18 and 70 |
Tumor Type | Glioblastoma Anaplastic Astrocytoma |
Karnofsky Score | Minimum 70 |
Effective treatment is lacking for malignant glioblastoma/astrocytoma. We have identified interleukin-4 receptors (IL-4R) on human malignant astrocytoma. We demonstrate that 16 of 21 surgical samples of high-grade astrocytoma and glioblastoma but not normal brain tissues expressed IL-4R as assessed by reverse transcriptase PCR. We further demonstrate that human malignant astrocytoma cell lines express high-affinity IL-4R. Using a chimeric protein composed of circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin A, we observed that this toxin (IL4(38-37)-PE38KDEL) is highly cytotoxic to IL-4R-bearing glioblastoma cells. Compared with a previously reported IL4-PE chimeric protein (IL-PE4E) IL4(38-37)-PE38KDEL bound with higher affinity and was 3-30 fold more cytotoxic to glioblastoma cell lines. Upon intrathecal administration in monkeys, high cerebrospinal fluid IL4(38-37)-PE38KDEL levels were not detectable in the serum of any monkey studied. When IL4(38-37)-PE38KDEL was injected into the right frontal cortex of rats, localized necrosis was observed at 1000-ng/ml doses but not at 100-ng/ml doses. We conclude that by localized administration, nontoxic levels of IL4(38-37)-PE38KDEL can be achieved, which may have significant cytotoxic activity against malignant astrocytoma.
Botulinum toxin injection therapy (also known as "BOTOX® therapy") is used to treatdystonia—a neuromuscular disorder that produces involuntary muscle contractions, or spasm—that affects muscles that control movement in the eyes, neck, face, limbs, voice box, or the smooth muscle in the bladder. The goal of the therapy is to reduce muscle spasm and pain.
This potent neurotoxin is produced by Clostridium botulinum, a bacterium that causes food poisoning (botulism). There are seven known types of C. botulinum toxin, but only types A; (BOTOX® Cosmetic) and B (Myobloc®) are used as medical treatments.
Botulinum toxin has proven to be useful in the treatment of many forms of dystonia, including the following:
Side Effects