MONDAY, Oct. 20, 2008 (HealthDay News) -- New discoveries in amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, and Alzheimer's disease could bring new hope to patients, scientists say.
In Alzheimer's, blocking a particular enzyme appears to improve memory and learning, a U.S. team says. And, in ALS, transplanting a type of stem cell can slow the degeneration of nerve cells, according to another study.
Both studies were published in the Oct. 19 online edition of Nature Neuroscience.
In the first report, researchers looked for ways to treat mice with an ALS-like condition.
"The study was designed to target a region where respiratory motor neurons reside -- the cervical spinal cord," explained lead researcher Dr. Nicholas Maragakis, a neurologist at Johns Hopkins University School of Medicine. "This site was chosen because most patients with ALS die of respiratory failure, and the motor neurons in humans reside in the cervical spinal cord," he added.
The researchers hypothesized that by replacing the diseased form of a common nerve cell called an astrocyte with a healthy version, they might preserve or postpone respiratory decline and thereby improve outcomes for ALS patients.
Maragakis' team found that the transplanted cells did survive in the mouse spinal cord. The ALS-affected mice also survived longer, although they were not completely cured.
The finding appeared to strengthen this new therapeutic approach.
"Astrocytes play a key role in disease progression in ALS models, and therapeutic approaches -- either targeting abnormal astrocytes or replacing diseased astrocytes with normal astrocytes through cell transplantation technologies -- may be relevant," Maragakis said. "The findings also stress that transportation of the enzyme glutamate, which is a primary function of astrocytes, appears to be a key to the neuroprotection offered by the 'normal' astrocytes," he added.
ALS is caused by degeneration and death of motor neurons -- nerve cells that stimulate muscles. However, based on the new findings, Maragakis said that non-neuronal cells, such as astrocytes, may be useful targets for therapy in ALS. That could change traditional treatment and cell-replacement therapies for this disease, he said.
The researchers have already been thinking about ways to deliver cells to ALS patients. "While such replacement strategies are not yet ready for the clinic, the next step is to use human astrocytes in the same ALS rodent model," Maragakis said. "If promising, we may propose future human ALS trials, although this is not imminent," he said.
Dr. Lucie Bruijn, science director and senior vice president of the ALS Association, said the research does hold promise.
"This might well be a therapeutic opportunity," Bruijn said. "The finding in these rodents is that you can slow the progression of the disease. But it's a big leap into the clinic," she cautioned.
"ALS patients are desperate for a therapy," Bruijn noted. "We have to be cautious; this is a laboratory study. It's a promise, it's a hope that might be meaningful if there are careful steps to translate it to humans."
In the second report, researchers led by Dr. Lennart Mucke, director, senior investigator and a professor of neurology and neuroscience at the Gladstone Institute of Neurological Disease in San Francisco, found that changing the metabolism of fatty acids could slow cognitive decline in mice afflicted with Alzheimer's.
"We discovered that an enzyme that clips off certain fatty acids from lipids in the brain seems to be activated by poisonous proteins [amyloid proteins] that build up in the brains of Alzheimer patients," Mucke said. "These fatty acids can do a lot of damage and impair memory."
In their experiments, Mucke's team noted that in mice with Alzheimer's, there was an increase in omega-6 fatty acid, known as arachidonic acid, and also its metabolic byproduct. This process is also involved in the production of amyloid-beta peptide, which is linked to the plaques and tangles in the brain that are a hallmark of the disease.
When the researchers blocked the activation of the arachidonic acid-metabolizing enzyme, they found that the mice had significant improvements in some learning and memory tasks.
"We were able to improve memory deficits and improve other behavioral abnormalities in these Alzheimer models," Mucke said. "This suggests that there may be a new therapeutic path where one could use inhibitors of this enzyme to prevent the release of detrimental fatty acids in the brain."
Since the researchers were able to prevent the progression of memory deficits, their next step is to see if they can reverse memory damage that has already occurred, Mucke said.
Dr. Samuel Gandy, Mount Sinai Professor of Alzheimer's Disease Research at the Mount Sinai School of Medicine in New York City and chairman emeritus of the National Medical and Scientific Advisory Council of the Alzheimer's Association, was less optimistic.
"It's an interesting new strategy," Gandy said. But since other methods of reversing amyloid-beta plaques have failed in human clinical trials, he wondered whether this latest attempt to do so will translate to a real benefit for patients.
"In general, making and curing mouse models of amyloid-beta toxicity has turned out to be relatively easy, but none of the 'mouse cures' have had any meaningful impact on human Alzheimer's disease," Gandy said.
More information
For more about neurological disease, visit the National Institute of Neurological Disorders and Stroke.
