The ALS Association Grants Ruxton Pharmaceuticals Funds to Develop Brain Imaging Compounds for ALS Research
By Richard Robinson, Science Writer

The ALS Association has awarded a multi-year research grant to Ruxton Pharmaceuticals, Inc., and their collaborators, John Gerdes, Ph.D. and Richard Bridges, Ph.D. at the University of Montana, to develop chemical compounds that may be used for brain imaging in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The compounds will be used to detect a protein on the surface of certain brain cells called astrocytes. These proteins, called glutamate transporters, are thought to be key regulators of potentially toxic chemicals in the brain. The transporters have been shown to be deficient in a large subset of ALS patients.

“These studies are crucial as we attempt to understand more about this important brain protein in ALS,” said Lucie Bruijn, PhD, science director and vice president of The ALS Association “and determine whether modulation of the transporter changes the disease course in ALS”.

Glutamate is a neurotransmitter used to send signals between brain cells. Too much glutamate is toxic to cells, and so brain cells use the glutamate transporter to remove it. In more than half of all ALS patients, the number of glutamate transporter molecules is reduced, which may contribute to the disease process.

“Glutamate plays an important, but not fully understood, role in ALS. These studies are designed to help shed light on this important area and to provide tools that some day could be used both to identify better drug candidates and identifying subtypes of patients – similar to the approaches used successfully in cancer chemotherapeutics,” said Jeffrey Rothstein, MD, PhD, of Johns Hopkins University, the scientific founder of Ruxton Pharmaceuticals, and a pioneer in studying astrocyte function and glutamate in ALS.

A significant unmet need in ALS is the ability to study the presence and function of astroglial cells and their glutamate transporters in the brains of living patients. In order to conduct such a study, the transporter must be “tagged” with a molecule called a radioligand. Developing this radioligand is the goal of the Ruxton project. The radioligand can be detected using PET (positron emission tomography) imaging, a standard tool in modern medical research.

“With this funding, we will be able to test and develop new ligands for the EAAT2 (excitatory amino acid transporter-2) glutamate transporter, which is the most prominent astroglial glutamate transporter in the human central nervous system,” said Rita Sattler, Ph. D, Research Associate at Johns Hopkins and leading the project for Ruxton. The studies will focus on characterizing and optimizing the brain penetration of candidate compounds, followed by pharmacologic testing and animal safety studies.

“The ability to study the glutamate transporter in ALS patients may provide us the opportunity to understand why some patients have low levels of this protein, while others do not,” Dr. Bruijn said. “It may also allow us to ask whether specific therapies can increase the level of glutamate transporter in these patients, and whether that can have any effect on disease progression.”

Dr. Richard E. Chipkin, President and CEO of Ruxton Pharmaceutical, Inc., thanked the ALS Association for supporting the company’s discovery efforts in this area. He added, “These new tools will help us to not only diagnose ALS, but will assist in our development of novel drugs to treat this terrible disease.”

Currently there is only one Food and Drug Administration (FDA) approved compound for ALS, riluzole, with modest effects on disease progression.

About ALS

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, first identified in 1869 by the noted French neurologist Jean-Martin Charcot. Although the cause of ALS is not completely understood, the past two decades have brought a wealth of new scientific understanding about the disease. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost, leading to progressive paralysis.

Lou Gehrig, with whom ALS is most commonly associated, first brought national and international attention to the disease in 1939 when he abruptly retired from baseball after being diagnosed with ALS.

About The ALS Association

The ALS Association is the only national, not-for-profit voluntary health organization devoted solely to fighting ALS through research, patient services, advocacy and public education and information.

The ALS Association’s TREAT ALS (Translational Research Advancing Therapy for ALS) program combines efficient new drug discovery with priorities set for existing drug candidates, to accelerate clinical testing of compounds with promise for the disease. For more information on TREAT ALS, please see The ALS Association's web site under the research tab (www.alsa.org/research/article.cfm?id=1048) and Laboratory Models in ALS (http://www.alsa.org/research/article.cfm?id=812).

About Ruxton Pharmaceuticals

Ruxton Pharmaceuticals (www.ruxtonrx.com) is focused on disorders of the brain, spinal cord, and peripheral nervous system. Its mission is to help patients with neurological disorders to live better and fuller lives. Their major research and development focus is on drugs affecting the astroglial proteins including glutamate transporters.