Technion turns goldfish into Parkinson's model

Judy Siegel-Itzkovich , THE JERUSALEM POST Jan. 20, 2008
http://www.jpost.com/servlet/Satelli...=1200572499500

The goldfish is an excellent model for studying Parkinson's disease and testing drugs to see which will be more effective in reducing symptoms and slowing progression of the degenerative neurological disease, according to an Israeli study just published in the prestigious journal Nature Protocols.

Parkinson's symptoms include body stiffness, tremors, slowed movement, impaired balance, frozen facial expressions, tiredness, apathy and sometimes pain, and slower mental processes.

Until the common fish was developed as a model for the disease by giving it the toxin MPTP, Parkinson's drugs were tested on humans, lower primates and other vertebrates. In the past, says Dr. Orly Weinreb, who edited the protocol for the model, it was reported that Parkinson's could be created in the Carassius auratus (common goldfish) by injecting a single dose of the toxin.

"Our research describes the simple and relatively cheap model of Parkinson's in goldfish. It takes 14 to 30 days, depending on the number of fish and the research program. The fish's nervous system is easily reached [and] the neuronal density and additional characteristics turn the model into an attractive system for studying Parkinson's and for developing potential drugs for the disease," she added.

After being injected with one dose, the fish begins to move slowly and shake. These symptoms are clearest three days after the injection. At the same time, the levels of dopamine and norepinephrine neurotransmitters in its brain are reduced. A product of the toxic oxidation of the MPTP (called MPP+) accumulates in various parts of the brain, penetrates the neurons and causes the cells to die. In addition, the toxicity of MPTP in the brain is blocked by monoamine oxidase B inhibitors, which are similar to the oral Parkinson's drug ragasiline.

Weinreb stated in her article that the fish model can now be used for other studies. "We proved that a Parkinson's drug can also work on fish and other organisms. The prototype of ragasiline [cured] the fish of the disease."

In addition, the blood-brain barrier in goldfish is more easily penetrated than that in humans, so it's easier to introduce drugs into its brain and test their influence. Ragasiline is currently under examination for use in Alzheimer's patients, as well. They drug apparently improves memory and learning and may also benefit mood, motivation and age-related memory decline in the aging but nominally healthy adult population.

The goldfish model was created by Prof. Moussa Youdim, a Teheran-born pharmacologist at the Technion-Israel Institute of Technology who developed ragasiline (Azilect), which is marketed by Israel's Teva Pharmaceutical Industries and whose use was approved by the US Food and Drug Administration two years ago. It has no known side effects.

Youdim has noted that the major problem of developing an animal model of the disease was that Parkinson's develops slowly over the course of several years, and most patients suffer from a type of Parkinson's whose cause is unknown. One can create human-like symptoms by injecting neurotoxins into fish, but as the disease in humans is not caused this way, animal models are best used for studying new ways to reduce symptoms, he explained. The models are inadequate predictors of disease-modifying agents, he added.

Youdim believes that in a few years, people might add daily liquid medications to food to prevent brain and nerve diseases and slow the aging process. Ragasiline, which shows up in the blood stream within 30 minutes of consumption and has been shown to slow the progression of the disease in animals and in some clinical trials, is used both in early-stage Parkinson's and, along with the drug levodopa, at a later stage of the disease's progression.