throughout the body. The tumor grows by creating new blood vessels from existing ones, but the cells are disor- ganized and tend to blood clotting and hemorrhaging. For most people, the first sign their dog has HSA of an inter- nal organ is that the dog suddenly col- lapses with signs of hypovolemic shock: weakness, white gums and extreme thirst, caused by internal bleeding from the tumor. Small bleeds may clot and go unnoticed; larger bleeds can be fatal. There are no reliable tests that can give an early warning that HSA is pres- ent. Once HSA is suspected, ultrasound can often detect a tumor, but it can’t determine if it’s HSA or a benign tumor. When possible, the tumor is surgically removed; but with the exception of HSA of the superficial skin layers, this is not curative. It simply eliminates the source of tumor cells and reduces the chance of a bleeding episode. But invariably the cancer has already spread. Chemo- therapy can delay the recurrence of a tumor elsewhere, but not prevent it. Less than 40% of dogs treated with sur- gery and chemotherapy survive beyond 6 months. Researchers at the University of Min- nesota have been foremost in the fight against HSA for the last decade. Now they have encouraging news with the announcement of a new drug regime that targets both tumor and tumor neo- vasculature. “eBAT” is an angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epider- mal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. You don’t need to understand that. Here’s the exciting part: When 23 sple- nectomized dogs with minimal stage I-II splenic HSA and minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin, 6-month survival rose from less than 40% in non-eBAT-treated dogs to about 70% in these dogs, with six dogs living
the bodies of dogs, including muscle and bone tumors, sarcomas, melanomas and lymphoma. It hasn’t cured them all, but results have been encouraging enough to set the stage for human clini- cal trials. Visit the HylaPharm website at www.hylapharm.com.
more than 450 days. While it’s not a cure, it’s the most significant treatment for extending life in HSA dogs to date. Reference: Antonella Borgatti, et al. “Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR”. Molecular Cancer Thera- peutics, 2017; molcanther.0637.2016 INJECTABLE TARGETED chemotherapy. But researchers at the University of Kansas are delivering it to dog cancer tumors in a new way. Rather than administer cisplatin so that it affects the entire dog, they created a drug named HylaPlat ™ , combining cis- platin with hyaluronan, a polymer that occurs naturally in the body. HylaPlat is injected directly into or near cancerous tumors. Tumor cells have a receptor for hyaluronan called CD44—this causes them to take up more of the HylaPlat than healthy cells. After doing its work in the tumor, HylaPlat drains into the lymph nodes, delivering a high dose of chemotherapy to any cancer cells there. By concentrat- ing the toxic chemotherapy drugs in the tumor and lymphatic nodes, less is circulating throughout the body. Dogs treated with HylaPlat have 75% less renal toxicity and 50% less liver toxic- ity compared to dogs treated with tradi- tional chemotherapeutic levels of cispl- atin. HylaPlat can treat any cancer that metastasizes through the lymph (that’s about 85% of cancers) and the same technology can be used with other che- motherapy drugs such as doxorubicin. Initial trials treating squamous cell tumors of the mouth in dogs were promising, so have now been followed by clinical trials to treat cancers all over CHEMOTHERA- PY TREATMENT Cisplatin is not a new drug in cancer
GENE THERA- PY TREATS A MUSCLE-WAST- ING DISEASE IN DOGS Gene therapy
holds the promise to treat many inher- ited diseases. A recent study shows its effectiveness in treating a fatal muscle- wasting disease of dogs, and possibly, humans. Dogs with myotubular myop- athy, or MTM, have a mutation in the gene that normally makes myotubular- in, a protein essential for proper muscle function. It occurs only in males, and affected dogs and children die early in life due to breathing difficulties. Now four collaborating research groups in the United States and France have found a way to replace the disease-causing MTM gene with a healthy gene through- out the entire musculature of affected dogs simply by a single infusion of the normal gene. Treated dogs were indistinguishable from normal dogs a year later. While it’s unlikely this therapy will be used for puppies with this disease, the treatment holds promise for affected children and also supports the effectiveness of gene therapy for skeletal muscle diseases in general. Reference: David L. Mack, et al. “AAV8- mediated gene therapy drives whole- body correction of myotubular myopa- thy in dogs”. Molecular Therapy, 2017 GENETIC CAUSE OF ONE TYPE OF EPILEPSY Also from the Uni- versity of Helsinki comes news of a new genetic cause of epilepsy. Far too many dogs suffer from seizures; in many cases the cause is unknown, in others a hereditary com- ponent is suspected. Now a collabora- tive study has found a gene associated with a type of epilepsy found in Rhode- sian Ridgebacks. Affected dogs develop myoclonic seizures around 6 months
“HYLAPLAT ™ CAN TREAT ANY CANCER THAT METASTASIZES THROUGH THE LYMPH (THAT’S ABOUT 85% OF CANCERS)...”
68 • S how S ight M agazine , M arch 2017
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