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From the Labs: Biotechnology

New publications, experiments and breakthroughs in biotechnology–and what they mean.
September 1, 2006

Growing Brain Cells
Drugs that trigger the birth of neurons could provide the next generation of treatments for neurodegenerative diseases such as Parkinson’s

A newly grown nerve fiber extends out of the spinal cord. (Courtesy of Annals of Neurology/John Wiley and Sons)

SOURCE: “Dopamine D3 Receptor Agonist Delivery to a Model of Parkinson’s Disease Restores the
Nigrostriatal Pathway and Improves Locomotor Behavior”
J. M. Van Kampenand C. B. Eckman
Journal of Neuroscience 26(27): 7272-7280

Results: Scientists at the Mayo Clinic in Jacksonville, FL, found that a drug similar to ones used to treat Parkinson’s disease can spur growth of new neurons in the substantia nigra, the brain area damaged in the disease. In a study of rodents genetically engineered to model Parkinson’s disease, twice as much neurogenesis, or birth of new neurons, was seen in animals treated with the drug as in control animals. Many of the newly generated cells appeared to develop into dopamine-producing neurons–the kind that are lost in Parkinson’s. In addition, treated animals showed an 80 percent improvement in motor ability.

Why it matters: Current treatments for Parkinson’s disease replace or mimic dopamine, an important signaling molecule in the brain. But those treatments lose their effectiveness over time; boosting the brain’s ability to make more of the dopamine-­producing cells could provide a more effective strategy.

Methods: Scientists treated rodents with a compound that triggers a dopamine receptor, delivering it directly to their brains for up to eight weeks. They then tracked the birth and development of new neurons and monitored the rodents’ performance in motor tasks.

Next steps: The team is now testing drugs currently used to treat Parkinson’s disease to see if they also trigger neurogenesis and, if so, how best to deliver these compounds to maximize effectiveness. Ultimately, they hope to find compounds that will help replace cells lost in a range of neurodegenerative diseases, such as Alzheimer’s and Huntington’s.

Stem Cell Mix Helps Paralyzed Rats Walk
Rodents regained mobility after receiving a combination of drugs and stem cells that rewired their nervous systems

SOURCE: “Recovery from Paralysis in Adult Rats Using Embryonic Stem Cells”
D. M. Deshpande et al.
Annals of Neurology 60(1): 32-44

Results: Scientists from Johns Hopkins University found that a complex combination of treatments, including stem cells and growth factors, can heal damaged neural circuits, allowing partially paralyzed rats to walk. According to the findings, 11 out of 15 rats with spinal-cord injuries regained some motor function after receiving the full battery of treatments.

Why it matters: Previous studies on paralyzed rats demonstrated the possibility of boosting the function of the nervous system and improving motor skills. But this is the first study to show that newly grown nerve fibers can emerge from the spinal cord, extend all the way to ­muscles in the rats’ haunches and limbs, and form functional connections with them. These findings represent a significant step forward in regenerative medicine, providing new treatment possibilities for some types of spinal-cord injury and for diseases in which motor neurons are damaged, such as amyotrophic lateral sclerosis (ALS).

Methods: The researchers transplanted motor neurons, derived from embryonic stem cells, into the spinal cord. Then they added a mix of growth factors to help the new cells survive and grow, as well as two chemicals known to block the signals that normally keep nerve fibers from growing out of the spinal cord.

In order to get the newly sprouted fibers to span the wide gap between the spinal cord and the muscles, the researchers injected neural stem cells into the target muscles. These cells produced a nerve growth stimulator that drew growing motor neurons to the muscle and allowed them to make functional neuromuscular connections.

Next steps: The team is now planning tests in pigs. Studies in larger animals are necessary to make sure that the new neurons can grow to great enough lengths that the treatment will work in humans. If those experiments are successful, the scientists say, human clinical trials could begin within five years.

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