Treating Neurodegenerative Diseases with Antibiotics

Timothy M. Miller and Don W. Cleveland

Cultures of spinal cord slices a

It is difficult to overstate the impact of penicillin and the family of P-lactam antibiotics since their introduction into clinical medicine in the early 1940s. These drugs act by inhibiting assembly of the protective outer wall of bacteria. Their impact on the treatment of a wide variety of infections has been nothing short of miraculous. But this family of wonder drugs from the last century may have yet more untapped therapeutic potential, as Rothstein and colleagues report in a recent issue of Nature (1). They demonstrate that certain P-lactam antibiotics have potential as neurotherapeu-tics for treating neurological diseases such as amyotrophic lateral sclerosis (ALS), adult motor neuron disease, and ischemic injury.

The evidence for this remarkable finding has arisen from a unique public-private partnership between the National Institute of Neurologic Disorders and Stroke of the NIH and a consortium of disease-oriented philanthropic organizations, including the ALS Association, the Huntington's Disease Society of America, and the Hereditary Disease Foundation. This consortium sponsored a drug screening effort that ignored the hundreds of thousands of compounds within the traditional chemical libraries mined by pharmaceutical companies. Instead, the consortium screened 1040 bioactive compounds, 750 of which were already approved by the FDA for use in humans. These compounds were then tested for their efficacy in multiple assays associated with one or more neurological diseases by 27 separate academic laboratories.

The first insight to emerge from this approach (see the figure, panel A) was a surprising new function for 15 P-lactam antibiotics, including penicillin and a more modern variant, ceftriaxone, that enters the brain by crossing the blood-brain barrier. These

The authors are at the Ludwig Institute for Cancer Research and the Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. E-mail: [email protected]

antibiotics selectively induce transcription of the gene encoding the EAAT2 glutamate transporter; other classes of antibiotics do not have these effects. Glutamate is crucial for normal signal transmission between many types of neurons, including the motor neurons whose job is to trigger muscle contraction and whose premature death produces the progressive paralysis characteristic of ALS. Upper motor neurons extend processes from the brain into the spinal cord, where they form synaptic attachments directly with the lower motor neurons or indirectly through intermediate neurons. The axonal processes of the lower motor neurons extend out of the spinal cord and form connections with mus-

Screen of 1040 FDA-approved medications and nutritionals for increased glutamate transport (spring 2002)

15 drugs from the penicillin family of ß-lactams identified

Upper motor neuron

Upper motor neuron ft1

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment