Scientists have successfully stopped the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, for nearly two years in mice, an advance that may lead to treatments for the fatal disease in humans.
“We are shocked at how well this treatment can stop the progression of ALS,” said lead author Joseph Beckman, professor at Oregon State University in US.
No treatment has been discovered for ALS that can do anything but prolong human survival less than a month.
ALS is known to be caused by the death and deterioration of motor neurons in the spinal cord, which in turn has been linked to mutations in copper, zinc superoxide dismutase.
Copper-ATSM is a known compound that helps deliver copper specifically to cells with damaged mitochondria, and reaches the spinal cord where it is needed to treat ALS.
This compound has low toxicity, easily penetrates the blood-brain barrier, is already used in human medicine at much lower doses for some purposes, and is well tolerated in laboratory animals at far higher levels.
Any copper not needed after use of copper-ATSM is quickly flushed out of the body.
Using the new treatment, researchers were able to stop the progression of ALS in one type of transgenic mouse model, which ordinarily would die within two weeks without treatment.
Some of the mice survived for more than 650 days, 500 days longer than any previous research has been able to achieve.
In some experiments, the treatment was begun, and then withheld. In this circumstance the mice began to show ALS symptoms within two months after treatment was stopped, and would die within another month.
However, if treatment was resumed, the mice gained weight, progression of the disease once again was stopped, and the mice lived another 6-12 months, the researchers said.
“We have a solid understanding of why the treatment works in the mice, and we predict it should work in both familial and possibly sporadic human patients,” Beckman said.
Familial ALS patients are those with more of a family history of the disease, while sporadic patients reflect the larger general population.
The transgenic mice used in these studies have been engineered to carry the human gene for “copper chaperone for superoxide dismutase,” or CCS gene.
CCS inserts copper into superoxide dismustase, or SOD, and transgenic mice carrying these human genes die rapidly without treatment.
After years of research, scientists have developed an approach to treating ALS that’s based on bringing copper into specific cells in the spinal cord and mitochondria weakened by copper deficiency.
Copper is a metal that helps to stabilise SOD, an antioxidant protein whose proper function is essential to life. But when it lacks its metal co-factors, SOD can “unfold” and become toxic, leading to the death of motor neurons.
The study was published in the journal Neurobiology of Disease.