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The Diagnosis: Two years ago it didn’t seem like an important event when my Mom began losing her nails but little did we know that it was just the beginning of a long period of searching for answers and significant pain. The nail loss began on her large toes and she and her doctor assumed it was a fungal infection. After trying several months of anti-fungal topical treatments without any success, she began two separate regimes of oral therapies. After almost a year it was clear that neither treatment was effective, and now she was also losing nails on her fingers. At this point, her dermatologist began to suspect a relatively rare condition – nail psoriasis. He began a course of topical treatments for psoriasis and recommended a nail bed biopsy to confirm the diagnosis. After a very painful procedure, the biopsy failed to identify psoriasis as the cause. During this period Mom began losing the nails on two more fingers on each hand. This symmetrical nail loss was now accompanied by the appearance of skin lesions.
Mom’s dermatologist recommended a consultation with another group of dermatologists who concurred with his diagnosis, noting that the biopsy probably did not sample the area of lesions at the nail growth site. The course of her disease then began to progress more rapidly. Mom’s joints on the affected toes and fingers began to swell and they became very painful. Her dermatologist began a series of monthly injections of the anti-inflammatory drug cortisone into where the nail growth originates. In spite of the very painful nature of the injections, Mom stuck with it for three months until it became clear that this treatment was not helping. After stopping this treatment, the swelling and pain in her joints on the affected fingers and toes increased significantly. It was now time to see a rheumatologist – Mom has all the signs of a quickly advancing case of psoriatic arthritis.
A recent survey conducted by the National Psoriasis Foundation (NPF) indicated that approximately 1 million US adults have been diagnosed with psoriatic arthritis. Psoriatic arthritis commonly affects the fingers and toes, and is generally difficult to diagnose in its early stages but that “early diagnosis, however, is important for preventing long term damage to joints and tissues”. If untreated this damage can have horribly disfiguring effects that make it difficult for patients to use their hands. Psoriatic arthritis is an inflammatory autoimmune disorder; its cause is uncertain but has been attributed to genetic, environmental, and immunologic factors.
A Treatment Made Possible Through Biomedical Research Using Animals: Mom’s rheumatologist recommended treatment with ENBREL (etanercept) a new biologic medication approved by the FDA in January 2002 to treat psoriatic arthritis. The development of this important new drug could not have happened without research using animals. Patients with psoriatic arthritis, psoriasis, rheumatoid arthritis and similar diseases have a chronic immune disorder in which a set of immune cells become overactive and release proteins called cytokines. One of these cytokines is Tumor Necrosis Factor (TNF) which works to regulate our body’s immune response to inflammation and infection. Patients with these conditions produce excessive amounts of the TNF chemical messenger which signals other cells that cause inflammation, skin lesions, and destruction of the joints. ENBREL is an anti-TNF therapy that binds to the overproduced TNF and makes it inactive.
The importance of TNF in the pathogenesis of these disorders was first confirmed utilizing mice that have been given collagen-induced arthritis. Studies with these mice revealed that they had elevated levels of TNF in their joints and that their arthritis could be prevented or reduced when given anti-TNF blocking antibodies.
Development of ENBREL also required the use of animals for testing and production. In 1989, Immunex began their effort to isolate the gene for the receptor of TNF. They were successful in isolating and cloning the TNF receptor but it took another 9 years to win approval for the release of one of the first biologic response modifier medicines. Once the right structure of the molecule, (called etanercept) was identified scientists went through a long testing phase using mice. Laboratory tests on these mice showed a dramatic reduction of arthritis and psoriasis. These encouraging results justified human trails and their success lead to its approval by the FDA. Animals also played a key role in the initial production of ENBREL. According to the manufacturer, “when the final form of etanercept was identified, the human DNA was introduced into Chinese hamster ovary cells, which would act as “factories” to produce the protein”.
Happily for my Mom, after over two years of blind alleys, painful tests and treatments, and no resolution in sight, she began taking ENBREL. Most remarkably, after only 6 weekly injections, the severe pain and swelling have disappeared and there are only two joints on the finger that was first affected that have damage that can not be reversed. The ‘miracle’ of Enbrel for my Mom clearly could not have happened without biomedical research using animals.
This summer I was extremely fortunate to have the opportunity to do my internship with the Department of Urology at the Arizona Health Sciences Center. Dr. Craig Comiter and Dr. Sanjay Ramakumar gave me the opportunity to assist in their research programs designed to develop new and effective treatments for urinary incontinence using minimally invasive surgical techniques.
My internship began with researching this topic using the Medical School Library’s on-line resources followed by readings and discussions with laboratory research staff. During my internship I was given the opportunity to receive training in the proper care of laboratory animals and direct experience in their experimental protocols. These involved measurement of leak point pressure of the urethra of the laboratory animals being studied as well as the effects of the naturally occurring hormone - angiotensin on the contracting muscles around the urethra. I was also given the opportunity to participate in the lab’s study of the effects of ICAM proteins in regard to ischemia-reperfusion injuries upon the kidney. After being instructed and observing proper techniques I was able to suture muscle and skin after these surgical procedures. Towards the end of my internship I was also given the opportunity to help with the analysis of the data I helped to collect and help to create a presentation on these results.
I was also excited about having the opportunity to actually observe surgeries performed by Dr. Ramakumar, train using the Arizona Simulation Technology and Education Center (ASTEC) specialized mannequin and on the laparoscopic surgery training system. I would like to thank Drs. Comiter and Ramakumar for giving me this opportunity; and extend a special thanks to the Hardeep and Mohammed, who were extremely helpful in teaching me so many new things. Their openness and patience helped to make this experience truly rewarding and reconfirmed my desire to work for a career in medicine.