Pharmacyclics' MGd improves survival rate in animal study of Lou Gehrig's

By Angela McDaniels

Seattle, Dec. 8 - Pharmacyclics Inc. said preclinical data shows that motexafin gadolinium (MGd) - the active chemical agent in Xcytrin Injection, the company's lead anti-cancer product candidate - increased survival in animal models of Amylotrophic Lateral Sclerosis, also known as Lou Gehrig's disease.

Researchers at the University of Arkansas for Medical Science, in collaboration with Pharmacyclics, measured the neuroprotective effect of MGd in a mouse model of Amylotrophic Lateral Sclerosis and found it increased expression of several proteins in the spinal cord known to be neuroprotective.

The study also demonstrated that mice receiving MGd after disease onset showed a 2.5 fold increase in survival and improved neurologic function versus control.

These findings suggest that MGd could be a useful therapeutic agent in Amylotrophic Lateral Sclerosis and other neurodegenerative diseases by inducing neuroprotective oxidative-stress-related proteins, the company said.

The data was presented at the 16th Annual International Symposium on Amylotrophic Lateral Sclerosis and Motor Neuron Disease in Dublin from Dec. 5 to Dec. 9.

A study published in the May 2005 issue of Cancer Research, the journal of the American Association for Cancer Research, reported on the effect of MGd in cancer cells and indicated that the drug induced the expression of oxidative-stress-related genes.

The publication proposed that various tissues in the body would respond differently to MGd-induced oxidative stress, the company said.

"Together, these studies suggest that MGd may have similar effects in cancer cells and neuronal tissue," said investigator John P. Crow in a company news release.

"In neuronal tissues, MGd-induced protein expression leads to neuroprotection. In cancer cells, the oxidative stress burden leads to cell death. These results may explain why patients with brain metastases in previous clinical trials experienced improved neurologic outcome when receiving whole brain radiation therapy in combination with MGd."

Amylotrophic Lateral Sclerosis is a progressive neurodegenerative disease that targets motor neurons that stretch from the brain to the spinal cord and from the spinal cord to the muscles throughout the body, the company said.

With all voluntary muscle action affected, patients in the later stages of the disease become totally paralyzed, yet in the majority of patients, cognitive function remains unaffected. Most Amylotrophic Lateral Sclerosis patients survive less than five years.

Pharmacyclics is developing Xcytrin as an anti-cancer agent designed to selectively concentrate in tumors and induce apoptosis (programmed cell death). Xcytrin is a redox active drug that disrupts redox dependent pathways in cells and alters oxidative-stress-related proteins, the company said.

Neuronal tissues, such as the brain and spinal cord, have high levels of oxygen consumption and metabolism and specialized biochemical processes aimed at ameliorating the effects of oxidative stress. MGd appears to induce oxidative-stress-related gene expression in neurons that are neuroprotective, the company said.

Pharmacyclics has been granted fast track status by the U.S. Food and Drug Administration for Xcytrin for the treatment of brain metastases in non-small cell lung cancer patients.

Pharmacyclics is a pharmaceutical company in Sunnyvale, Calif., that develops small molecule drugs products to treat cancer, atherosclerosis and other diseases.

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