Gene Therapy May Be Answer to Effective Parkinson’s Treatment; Neurolucida Plays Role in Study

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Neurotrophic factors may be the key to the cure for Parkinson’s, Huntington’s, Alzheimer’s, and other neurodegenerative disorders. Scientists have known this for over twenty years. But the question continues to loom – how does one safely and effectively deliver the neurotrophic factors to the damaged neurons? Dr. Raymond Bartus and his team at Ceregene, a biotechnology company in San Diego, have developed an innovative approach that may be the answer.

Rather than focusing on conventional methods of neurotrophic factor delivery, which have always been extremely difficult and resulted in undesirable side effects, the Ceregene researchers took a different approach. They turned to gene therapy. Instead of delivering the restorative protein to the targeted sites in the brain, the Ceregene researchers developed a way to deliver only the gene for the protein. Once in place, the gene induces local cells to make the protein on site.

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Congratulations to Timothy Collier, PhD., Recipient of the Bernard Sanberg Memorial Award for Brain Repair

We’d like to extend our congratulations to one of our customers, Dr. Timothy Collier, recipient of the 2012 Bernard Sanberg Memorial Award for Brain Repair. Presented each year by the American Society of Neural Therapy and Repair, the award is given to an individual who has made outstanding research contributions in the field of neural therapy and repair, and we agree, Dr. Collier is certainly worthy of this recognition.

A professor of translational science and molecular medicine at Michigan State University and director of the Udall Center of Excellence in Parkinson’s Disease Research at Michigan State University and the University of Cincinnati, Dr. Collier has devoted his career to researching the neurobiology of aging. He has studied the role of dopamine in neuron biology as applied to aging, Parkinson’s disease, and experimental therapeutics, and was part of a team that first examined cell transplantation in nonhuman primate models of Parkinson’s disease.

“Professor Collier has been a leader in the field of cellular repair for Parkinson’s disease for over 25 years and consistently has brought new ideas forward on how to stimulate growth and survival of neurons that are crucial for maintenance of proper brain function,” said John Sladek, PhD, director for Outreach and Development, Center for Neuroscience, and professor of Neurology, Pediatrics and Neuroscience at the University of Colorado School of Medicine. “As director of the highly coveted Morris Udall Center of Excellence for Parkinson’s Disease Research he is in an ideal position to make breakthroughs that will accelerate the transfer of new research into the clinics. As his postdoctoral mentor, I couldn’t be prouder of his accomplishments and look forward to his next important discovery.” (ASNTR Press release, 5.29.2012)

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Washington University Researchers use Stereo Investigator to Study Axonal Transport in Parkinson’s Model

Journeying along axons, microscopic powerhouses known as mitochondria provide cells with the energy they need to function. When something goes wrong with the axonal transport and mitochondria isn’t delivered, the system fails, and the cell body dies.

Scientists in the Department of Anatomy and Neurobiology at the Washington University School of Medicine in St. Louis study the cellular bases of neurological disorders. Their recent research focuses on Parkinson’s disease and identifies impaired axonal transport as a possible key player in this neurological disorder.

The research group, of Dr. Karen L. O’Malley, Dr. Jeong Sook Kim-Han, and Dr. Jo Ann Antenor-Dorsey studied axonal transport in dopamine (DA) neurons in the mouse brain—the cells most affiliated with Parkinson’s disease. They localized cell axons by using a microchamber system that separated axons from cell bodies and dendrites. They also introduced 1-methyl-4-phenylpyridinium ion (MPP+), a toxin known to disrupt axonal function and mimic Parkinson’s disease.

Stereo Investigator helped them quantify TH-positive cell bodies and neurites. As early as 12 hours after MPP+ treatment, they saw breaks in axons. After 24 hours, they began to see a significant reduction in cell bodies. “This study underscores the necessity of developing therapeutics aimed at axons as well as cell bodies so as to preserve circuitry and function,” they say in their paper “The Parkinsonian Mimetic, MPP+, Specifically Impairs Mitochondrial Transport in Dopamine Axons, published in the Journal of Neuroscience.

The use of Stereo Investigator saved the researchers time and hard drive space, according to Dr. Kim-Han. “We used to count cells after acquiring images from a fluorescent microscope and saving it to a computer, which took long time and a lot of space on the computer,” she said. “Also, the data was more convincing since the area for counting was selected automatically with the number of fields assigned.”

Read the full paper “The Parkinsonian Mimetic, MPP+, Specifically Impairs Mitochondrial Transport in Dopamine Axons“, in the Journal of Neuroscience.

[The Journal of Neuroscience, 11 May 2011, 31(19): 7212-7221; doi: 10.1523/ JNEUROSCI.0711-11.2011]

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{IMG: Synapse Diagram – This file is licensed under the Creative Commons Attribution-Share Alike 1.0 Generic license}

Gene Therapy Improves Parkinson’s Symptoms

Patients suffering from Parkinson’s disease may have a new way to manage their illness: gene therapy. Scientists at seven leading gene therapy centers across the US saw improvements in patients when a gene that helps produce the inhibitory transmitter GABA was introduced to quiet the subthalamic nucleus, an overactive region of the brain in Parkinson’s patients.

Twenty-two subjects from a group of 45 patients aged 30-75 received AAV2-GAD infusions, while the rest underwent sham surgery. Over the course of six-months, the group that received gene therapy showed significant improvement in Parkinson’s symptoms, according to a study published this month in The Lancet Neurology.

Encouraged by the success of the trial and safety of the method, the investigators, including MBF Bioscience customer Dr. Michael G Kaplitt of Weill Cornell Medical College, plan to further their research with a larger clinical trial.

Read more about the study at nature.com and access the abstract and full article text at thelancet.com.

LeWitt, P. A. et al. Lancet Neurol. doi:10.1016/S1474-4422(11)70039-4 (2011).

Stanford’s Dr. Karl Deisseroth Featured in Wired Magazine

Optogenetics is a fairly new scientific field that combines optical stimulation with genetic engineering. According to a recent article in Wired magazine, neuroscientist, psychologist, and MBF Bioscience customer Dr. Karl Deisseroth and his team of researchers at Stanford University are making major optogenetic advancements – the kind that might lead to a cure for Parkinson’s Disease.

It all began in 1979, when one of the discoverers of DNA’s double helix, Francis Crick, acknowledged the need to “control neurons of only one cell type in one specific location.” The solution?  Light. The only genes known to respond to light were the ones found in plants. In the 1990s, German biologist Peter Hegemann was researching the affect of light on algae. When exposed to light, the algae cells moved.

Ten years ago, UC San Diego biologist Roger Tsien acquired some of Hegemann’s light-sensitive genes, and inserted them into a frog egg. Stimulated by a beam of light, the egg responded.

Enter Dr. Deisseroth. Aided by a team of graduate students, Dr. Deisseroth set out to discover whether or not “misbehaving cells” in the brains of patients suffering from depression or Parkinson’s could be “tagged genetically and controlled with light.” They were able to successfully control the movements of worms, make a mouse run in circles, and are currently carrying out research on primates.

Read the full article at wired.com to find out more about the history of optogenetics and its relevance to the treatment of Parkinson’s.