April 4, 2006
Antisense, Other Therapeutic Progress Highlighted at AAN
Scientific presentations at the American Academy of Neurology (AAN) on Tuesday highlighted antisense research and other therapeutic progress for ALS (amyotrophic lateral sclerosis).
Following the presentation of the 2006 Sheila Essey Award were presentations on more progress in finding new therapies for ALS, led by a talk by Timothy Miller, M.D., Ph.D., of the Ludwig Institute at the University of California, San Diego (UCSD), on antisense therapies for the disease. Miller and colleagues, funded by ALSA and Isis Pharmaceuticals, have screened for the ability of antisense molecules to lower the expression of the mutant protein linked to some inherited forms of ALS, copper-zinc superoxide dismutase (SOD1). Antisense treatment near onset of symptoms significantly slowed disease progression in rats that have the G93A mutation to SOD1.
A Phase I trial of antisense in 16 patients could begin in 2007. As antisense drugs can be readily manufactured in commercial quantities and their delivery regulated by altering the dose or frequency of administration, this approach holds immediate promise for treating ALS and other degenerative disorders of the nervous system, Miller said.
The team led by Stanley H. Appel M.D. at Methodist Hospital in Houston presented findings on the role of microglia in ALS, which support similar work in the UCSD lab of Don Cleveland, Ph.D., reported in a poster later in the meeting. Appel’s group found that microglia, which express mutant SOD1, are more toxic when grown in the lab with motor neurons.
Investigators working with Stuart A. Lipton, M.D., Ph.D., of UCSD, presented a new model for motor neuron disease. They have produced a mouse without the gene for part of a type of glutamate receptor, called the NR3B subunit, in motor neurons. Mice lacking this part of the glutamate receptor begin to show profound limb weakness, especially of the hind limbs, three days after birth. The mice pups died in the next two to three days, probably due to inability to feed or breathe. Their tissues showed a severe loss of motor neurons in the spinal cord, especially in the lumber region, with about half the motor neurons missing there. Fibers also were lost in the nerve roots exiting the cord and from the phrenic nerve to the diaphragm. As the defect appears specific for motor neurons, these mice hold promise for a new way to test potential ALS therapeutics.
To read more about ALS research at AAN, click here.
