Copper compound could form basis for first Lou Gehrig's disease therapy

Lou Gehrig's disease - also known as amyotrophic lateral sclerosis - is an incurable, fatal disease that affects as many as 30,000 individuals in the US. But a new study published in the Journal of Neuroscience suggests a copper compound could be used in therapy for the condition.

The researchers, from Australia, the US and the UK, demonstrated in mice that oral administration of this compound extended lifespan and improved locomotor function of transgenic mice genetically engineered to develop amyotrophic lateral sclerosis (ALS).

ALS is a rapidly progressing, fatal neurological disease that attacks the nerve cells that are responsible for controlling voluntary muscles.

It is characterized by the gradual degeneration and death of motor neurons - nerve cells in the brain, brain stem and spinal cord that communicate between the nervous system and voluntary muscles of the body.

Because the upper and lower motor neurons degenerate or die with ALS, they stop sending messages to the muscles. Eventually, the brain's ability to initiate and control voluntary movement ceases.

Researchers say a copper compound could potentially increase lifespan of individuals with ALS, a fatal neurological disease.

Most people with the condition die from respiratory failure within 3-5 years from onset of symptoms, but around 10% survive for 10 years or more.

The researchers, led by Prof. Joseph Beckman of the Oregon State University College of Science, say that so far, no therapy for ALS has ever been able to extend lifespan for more than a few extra months in humans.

However, they add that their newly discovered approach could change this, potentially helping with Parkinson's disease treatments as well.

Compound increased lifespan by 26%

The team explains that ALS has been traced to mutations in copper, zinc and superoxide dismutase - an antioxidant also known as SOD1. Normally, the proper function of SOD1 is essential to life, but when it lacks its metal co-factors, it becomes toxic, "unfolding" and resulting in the death of motor neurons.

According to the team, copper and zinc help to stabilize the protein, keeping it folded for more than 200 years.

The research team explains this process further:

"The damage from ALS is happening primarily in the spinal cord and that's also one of the most difficult places in the body to absorb copper. Copper itself is necessary but can be toxic, so its levels are tightly controlled in the body.

The therapy we're working toward delivers copper selectively into the cells in the spinal cord that actually need it. Otherwise, the compound keeps copper inert."

The researchers believe that by recovering the proper balance of copper in the brain and spinal cord, they are stabilizing SOD1 in its mature form, improving the function of mitochondria.

The compound they use is called "copper (ATSM)," which has been previously studied for use in cancer treatments and is inexpensive to create.

In the mouse study, the researchers observed that lifespans extended by 26%, and they believe with further research, they can extend this increase further.

A research fellow at the University of Melbourne in Australia, says their results were the opposite of what they expected:

"The treatment increased the amount of mutant SOD, and by accepted dogma this means the animals should get worse. But in this case, they got a lot better. This is because we're making a targeted delivery of copper just to the cells that need it."

Approach could also help with Parkinson's therapy

Though no cure has been found for ALS, the Food and Drug Administration approved the first drug treatment for the disease in 1995. Called riluzole (Rilutek), it is believed to reduce motor neuron damage by decreasing the release of glutamate.

Fast facts about ALS

• An estimated 5,000 people in the US are diagnosed each year with the disease
• ALS is one of the most common neuromuscular diseases worldwide
• Though younger and older people can develop it, ALS typically strikes people between 40-60 years old
• Men are affected more than women.

In 90-95% of all ALS cases, the disease occurs at random, with no clear risk factors, and individuals with this form of the disease do not have a family history of ALS.

The onset of ALS is often so subtle that symptoms are overlooked. These include: cramps, spasticity, muscle weakness, slurred and nasal speech, or difficulty chewing or swallowing.

These symptoms then rapidly develop into more obvious weakness or atrophy that typically signals a physician that ALS may be present.

Though it is a debilitating condition, the research team team "believes that with further improvements, and following necessary human clinical trials for safety and efficacy," their approach could provide not only a new therapy for ALS, but also potential therapies for Parkinson's disease.

Researchers recently reported on a study that suggested an origin for Lou Gehrig's disease. Researchers from that study identified a fault in protein formation, which led them to suggest ALS is "misregulation of one step in the production of the neurofilament."