No Aminopterin in Tissues of Animals Killed by Recalled Pet Food

AUBURN, Wash., March 30 /PRNewswire/ -- Researchers from Syntrix Biosystems, Inc. and The University of Medicine and Dentistry of New Jersey (UMDNJ) announced today that there was no evidence of Aminopterin in the tissues of animals who had died from consuming food from Menu Foods, the manufacturer of the many brands of dog and cat food that are currently the subject of a nationwide recall.

"We became concerned when Aminopterin was implicated as the toxin in the recent pet food recall. The clinical pattern did not fit the known toxicology of Aminopterin," said John A. Zebala, M.D., Ph.D. President and CEO of Syntrix Biosystems. "We immediately reached out and offered our expertise to other investigators in the field who had reported finding the compound in food samples."

Using a highly specific and sensitive test for Aminopterin, investigators at UMDNJ documented that there was no evidence of Aminopterin in the tissues of affected animals. "Aminopterin persists in the liver of animals for months at levels that are readily detected," said Barton A. Kamen, M.D., Ph.D. Professor of Pediatric Oncology at UMDNJ. "Whatever is causing the renal failure, it is not Aminopterin." These results are completely consistent with the findings of the FDA, who announced today that they found no evidence of Aminopterin in food samples.

The reference to the use of Aminopterin as a rodenticide (i.e. rat poison) dates back to a 1951 patent issued to the American Cyanamid Company that is commonly cited by a variety of reference textbooks including the Merck Manual.(1) "To our knowledge, Aminopterin is not, and has never been, actually used as a rodenticide. The preparation of the molecule is complex and expensive. It is also unstable in the environment due to degradation by light and heat," said Dr. Zebala.

The FDA Office of Orphan Products Development has supported Dr. Kamen with grants for the clinical testing of Aminopterin in pediatric leukemia. "We have found that Aminopterin has unique properties relative to other drugs in its class that hold significant clinical promise and which we are very excited about," said Dr. Kamen. "Since our clinical development program began, we have safely treated over 100 patients with Aminopterin in Phase 1 and Phase 2 clinical trials. Many patients have been treated for over 2 years with Aminopterin and are disease free after 5 years."

Syntrix Biosystems, Inc. acquired the exclusive rights to Aminopterin from UMDNJ in February 2003. The company aims to market Aminopterin for the treatment of inflammatory and oncology disorders in both veterinary and human markets. "We see Aminopterin as the next blockbuster drug in clinical development with a market potential of over 4 million prescriptions per year," said Dr. Zebala.

Aminopterin was first used by Dr. Sydney Farber of the Harvard Medical School to induce temporary remissions in patients with acute leukemia as reported in the New England Journal of Medicine.(2) It was later marketed by Lederle Laboratories in the United States from 1953 to 1964 for the indication of pediatric leukemia. The drug was discontinued by the company due to manufacturing difficulties before its advantages could be appreciated by scientists.

During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in the United States, producing dramatic clearing of lesions.(3) The National Institutes of Health (NIH) has recently awarded Syntrix Biosystems $800,000 to support the clinical testing of Aminopterin in psoriasis.

Dr. Zebala said, "the exciting and unique clinical properties of Aminopterin promise to make this the first-line agent for treating psoriasis, as well as a variety of other human autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, polymyositis, multiple sclerosis, ulcerative colitis and Crohn's disease to name a few."

Syntrix Biosystems has also conducted a clinical trial of Aminopterin in canine atopic dermatitis, a common inflammatory disease affecting up to 15% of dogs. "There was dramatic improvement in disease scores in dogs treated with a single weekly dose of Aminopterin for up to 40 weeks with no evidence of toxicity," said Dr. Zebala. "This is a devastating disease for both dogs and pet owners, and having a convenient, highly effective and well tolerated treatment will be a major improvement in its management."

Dr. Zebala emphasized by saying, "Aminopterin is one of the most promising new therapeutic drugs in investigational clinical development for both humans and animals. In order for animals affected by contaminated pet food to be properly and accurately treated, it is critical that veterinarians know as soon as possible that Aminopterin is not the causative agent."

Syntrix Biosystems is a privately held pharmaceutical company located in Auburn, WA. The Syntrix Biosystems website is located at http://www.syntrixbio.com/.

(1) Alfred L. Franklin. United States Patent Number 2,575,168. "Rodenticide comprising 4-amino-pteroylglutamic acid." American Cyanamid Company, New York, NY. November 13, 1951.

(2) Farber, S., L. K. Diamond, et al. "Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl- glutamic acid (aminopterin)" The New England Journal Of Medicine. Volume 238, page 787, Jun 3, 1948.

(3) Rees, R. B., J. H. Bennett, et al. "Aminopterin for psoriasis: A decade's observation." The Archives of Dermatology. Volume 90, page 544, 1964.