HFS!

Here's a press release from a company that was started by a leading ALS researcher. They apparently did the study in mice and rats, not humans, but I am contacting my neurologist to see if I should get on the antobiotic:

Drugs Discovered That May Slow Progression of Lou Gehrig's Disease

Small Molecule Drugs Turn on Protective Gene

BALTIMORE, MD -- (MARKET WIRE) -- 01/05/2005 -- A family of existing antibiotics may help prevent nerve damage and death in neurological injury including amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), according to a report in the January 6, 2005, issue of Nature. The findings may be applicable to a wide variety of neurodegenerative diseases as well as to other neurological diseases including epilepsy, peripheral neuropathy, and disorders of learning and memory.

The authors demonstrated that ceftriaxone, a beta-lactam antibiotic, turns on a gene that encodes for the glutamate transporter GLT-1. As a result, more glutamate transporter protein is present and functioning in the brain; the authors showed this to be protective against brain cell degeneration.

The newfound ability of ceftriaxone, other beta-lactam antibiotics, and other classes of drugs to activate glutamate transporters and to protect nerves, and the drugs' potential therapeutic use in a wide range of neurological and psychiatric conditions, are covered by patent applications held by The Johns Hopkins University and licensed to Ruxton Pharmaceuticals, Inc. The work described in the Nature article is being extended in part under a sponsored research agreement by Ruxton Pharmaceuticals, Inc., with Johns Hopkins.

Glutamate is the most abundant neurotransmitter in the brain. Glutamate transporters clear the neuronal synapses of excess glutamate similar to the way an air vent circulates and clears the air in a room. Too much glutamate resulting from too few glutamate transporters, as is observed in neurodegenerative diseases, overexcites nerve cells and harms them, a process called glutamate excitotoxicity. Excess synaptic glutamate has long been known as a source of nerve damage in neurodegenerative diseases such as ALS, Parkinson's, and multiple sclerosis. Making more transporter molecules, however, seems to counter that.

More than a dozen beta-lactam antibiotics were among protective agents identified by a National Institutes of Health-funded project to screen 1,040 Food and Drug Administration-approved drugs and nutritionals for new uses. "Ceftriaxone was neuroprotective in vitro when used in paradigms of ischemic injury [stroke] and motor neuron degeneration, both based in part on glutamate toxicity," writes principal author Jeffrey D. Rothstein, M.D., Ph.D., director of the Robert Packard Center for ALS Research at Johns Hopkins and Professor of Neurology and Neuroscience at Johns Hopkins. Dr. Rothstein is the scientific founder of Ruxton Pharmaceuticals and is a paid consultant to the company.

People with ALS normally experience progressive weakness, paralysis, and death within three to five years of diagnosis. In mouse models of ALS, daily injections of ceftriaxone given after symptoms have developed delayed both nerve damage and the outward signs of the disease. Mice on ceftriaxone also lived significantly longer than those who got no drug. Normal rats and mice that received daily ceftriaxone for up to a week had triple the usual amount of the transporter in cells, an effect that lasted some three months after treatment.

"Overall, these studies document a new property of a very common antibiotic and demonstrate that beta-lactams can activate the gene for a neurotransmitter transporter," the researchers write in Nature.

"Although these drugs were tested in a mouse model of ALS, this discovery is much bigger than ALS," said David S. Block, M.D., President and CEO of Ruxton Pharmaceuticals. "This approach has potential applications in numerous neurologic and psychiatric conditions that arise from abnormal control of glutamate. In diseases such as ALS, we hope that this approach might eventually deliver drugs that can be used in combination with other approaches, similar to combinations used in HIV and oncology."

The research was funded by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins. The ALS mice were provided by Project ALS.

About Company

Founded in 2004, Ruxton Pharmaceuticals is an emerging pharmaceutical company that has been formed to discover, develop and market drugs for the treatment of neurodegenerative and other neurological diseases. Ruxton is focused on important indications with serious unmet medical needs such as ALS or "Lou Gehrig's" disease.

And here is the Eureka Alert:

Public release date: 5-Jan-2005

Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions


Antibiotics protect nerves in mice by turning on genes


Large, multi-center clinical trial planned in Lou Gehrig's disease
A family of antibiotics that includes penicillin may help prevent nerve damage and death in a wide variety of neurological diseases, including Lou Gehrig's disease, dementia, stroke, and epilepsy, Johns Hopkins researchers have found.

The antibiotics' beneficial effects, discovered in experiments in the lab and with mice, are unrelated to their ability to kill bacteria, the researchers report in the Jan. 6 issue of Nature. Instead, the drugs squelch the dangerous side of a brain chemical called glutamate by turning on at least one gene, thereby increasing the number of "highways," or transporters, that remove glutamate from nerves.

"It would be extremely premature for patients to ask for or take antibiotics on their own," says the study's leader, Jeffrey Rothstein, M.D., Ph.D., director of the Robert Packard Center for ALS Research at Johns Hopkins and a professor of neurology and of neuroscience. "Only a clinical trial can prove whether one of these antibiotics can help and is safe if taken for a long time."

In mice engineered to develop the equivalent of Lou Gehrig's disease, daily injections of an antibiotic called ceftriaxone, started just as symptoms tend to surface, delayed both nerve damage and symptoms and extended survival by 10 days compared to untreated animals. Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS), in people causes progressive weakness and paralysis and ends in death, usually within three to five years of diagnosis.

"We're very excited by these drugs' abilities," says Rothstein. "They show for the first time that drugs, not just genetic engineering, can increase numbers of specific transporters in brain cells. Because we study ALS, we tested the drugs in a mouse model of that disease, but this is much bigger than ALS. This approach has potential applications in numerous neurologic and psychiatric conditions that arise from abnormal control of glutamate."

A large, multi-center clinical trial planned for the spring will help determine the best dose of and schedule for ceftriaxone in people with ALS, and will measure whether the known risks of long-term antibiotic treatment are worth it, he says. The drug is currently approved by the U.S. Food and Drug Administration and used to treat bacterial infections in the brain.

More than a dozen of penicillin's relatives, known as beta-lactam antibiotics, were among protective agents identified by a National Institutes of Health-funded project to screen 1,040 Food and Drug Administration-approved drugs for new uses. The newfound ability of these antibiotics to activate glutamate transporters and to protect nerves, and the drugs' potential therapeutic use in neurological conditions, are covered by patent applications held by Rothstein and Johns Hopkins and licensed to Ruxton Pharmaceuticals Inc.

Of the antibiotics, penicillin protected nerve cells best in laboratory dishes, but ceftriaxone had the best results in mice, probably because it more easily crosses into the brain from the blood, the researchers report.

Rothstein and his colleagues determined that the antibiotics' benefit stems from their newly recognized effect on glutamate's Jekyll-and-Hyde effects. In the brain, glutamate normally excites nerves so that electrical signals can travel from one to the next. But too much of the chemical can overstimulate and kill nerves, a factor in ALS and some other diseases.

In a series of experiments, the researchers discovered that the antibiotics activate the gene encoding glutamate's main transporter in brain cells. Rats and mice that received daily ceftriaxone for up to a week had triple the usual amount of the transporter, known as GLT1, in their brain cells, an effect that lasted for up to three months after treatment.

"Glutamate is just one of many messengers brain cells use to communicate with one another, and this is just one of the transporters that move glutamate," says Rothstein. "So if you can find the right drug, you might be able to specifically affect other transporters, too."

Because ceftriaxone only protects against glutamate damage, just one problem in ALS, it's not surprising that the mice eventually succumbed to weakness and paralysis despite treatment, he says.

"If we can find drugs that protect against other causes of nerve death in ALS, the combination might offer a real therapy, much like using drug combinations to treat cancer," says Rothstein. "The more we know about ALS and other neurological diseases, the better our chances of finding ways to prevent nerve death by all causes."

The research was funded by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins. The ALS mice were provided by Project ALS.

Authors of the paper are Rothstein, Sarubhai Patel, Melissa Regan, Christine Haenggeli, Yanhua Huang, Dwight Bergles, Lin Jin, Margaret Dykes Hoberg, Svetlana Vidensky, Dorothy Chung and Shuy Vang Toan, all of Johns Hopkins; Lucie Bruijn of The ALS Association; and Zao-zhong Su, Pankaj Gupta and Paul Fisher of Columbia University Medical Center.

###


Under a licensing agreement between Ruxton Pharmaceuticals Inc. and The Johns Hopkins University, Rothstein is entitled to a share of royalty received by the University on sales of products described in this study. Rothstein and the University own Ruxton Pharmaceuticals Inc. stock, which is subject to certain restrictions under University policy. Rothstein is a paid consultant to Ruxton Pharmaceuticals Inc. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

On the Web:
http://www.nature.com/nature