Investing in Breakthroughs
The Jurenko name is indelibly linked with the UAB Department of Neurology, so consistent has been the Huntsville couple’s support of the department’s goals. Since 2007, John Jurenko, the retired vice president of sales and marketing at ADTRAN, a company he co-founded in 1985, and his wife, Ruth, have made gifts to advance numerous initiatives within the department. Among these are the John A. and Ruth R. Jurenko Neurological Research Laboratory, the John A. and Ruth R. Jurenko Research Scholar Fund, and the UAB-HudsonAlpha Collaborative Project in the Genetics and Genomics of Parkinson’s Disease.
Their latest gift, to establish the John A. and Ruth R. Jurenko Endowed Professorship in Neurology, enabled department chair David G. Standaert, M.D., Ph.D., to recruit one of the country’s leading Parkinson’s disease researchers. In 2007, Andrew B. West, Ph.D., was recruited from Johns Hopkins University to UAB, where he was named the John A. and Ruth R. Jurenko Research Scholar and became director of the John A. and Ruth R. Jurenko Neurological Research Laboratory in the UAB Center for Neurodegeneration and Experimental Therapeutics (CNET). In February 2013, he became the inaugural holder of the John A. and Ruth R. Jurenko Endowed Professorship in Neurology.
John Jurenko first encountered the Department of Neurology as a Parkinson’s patient, but was quickly impressed by the innovative research taking place. “My original contact with the department was because of the disease, but then I got to know the people there. They are exceptional people, both professionally and personally,” he says. “In discussion with them, I learned that they wanted to grow the department, and I figured I could help. They mentioned Andy West and his talent and that they’d like to have him. So I said, ‘Well, let’s go get him.’”
According to Standaert, philanthropic support like the Jurenkos’ has been key to making the UAB Department of Neurology and its associated divisions and centers the hives of innovation they are today. “Almost all of the major faculty recruitments we have done have been based on philanthropic gifts,” he says. “Their willingness to support our vision has enabled the tremendous growth we have experienced in less than a decade. When I first came to UAB in 2006 to lead CNET, it was just me. Now the center comprises more than 50 scientists, students, postdocs, and staff.” This philanthropic investment in research has contributed to an explosion in Parkinson’s discoveries, Standaert says. “The amount we’ve learned in the past five years exceeds everything we knew from the previous 200 years. We are deeply grateful to John and Ruth Jurenko for helping us achieve so much in such a relatively short period of time.”
According to West, “Meaningful advances in neurodegeneration research are very hard won. The John A. and Ruth R. Jurenko Professorship in Neurology allows us to accelerate the process and provides key resources to address critical questions that can’t wait for traditional funding mechanisms. With the support of the Jurenkos, we can focus on addressing critical bottlenecks and hasten the identification of novel neuroprotective therapeutics.”
New device to control seizures proving its worth
In that short time, she can already say, “I’m doing pretty good."
Conner, 24, has suffered from seizures for 10 years. In June, she became the first patient in the Southeast to receive a new device called a responsive neurostimulator since its approval by the Federal Drug Administration last year.
UAB neurosurgeon Kristen Riley, M.D., implanted the RNS system, developed by NeuroPace, into Conner’s brain. It includes an electrical generator, about the size of a flash drive, which is implanted in the skull. Electrodes are run to the locations in the brain known to cause seizures.
“It is designed to record a patient’s specific brain activity and recognize patterns that are associated with seizures,” said Riley, associate professor in the Department of Neurosurgery. “The RNS system then delivers stimulation in order to help modulate and control the seizures.”
Prior to receiving the RNS system, Conner experienced multiple semi-partial seizures every day, lasting anywhere from 10 seconds to more than a minute. When they hit, she lost all ability to function.
“It affected my motor function and sensory perception,” Conner said. “I couldn’t tell where my hand was, for instance. I couldn’t even do simple functions such as open a door because my body wouldn’t respond. It was as if I’d forgotten how to do it.”
A month after the surgery, UAB neurologist Neil Billeaud, M.D., turned on the device. At a follow-up visit 30 days later, Conner reported dramatic improvement.
|“This is not a treatment that will cure epilepsy. This is a treatment that will help control seizures in a very specific group of patients who otherwise are not candidates for surgery. I don’t expect too many patients to become seizure-free; but if we can decrease their seizures by even half, we can make huge improvements in their lives.”|
The RNS system is constantly recording Conner’s brain activity, and the data is downloaded to a laptop computer. If Conner says she had a flash last week, Billeaud can pinpoint the specific time and see what brain activity was occurring. As the system learns more about specific patterns that indicate a seizure is likely, Billeaud can tweak the parameters to make the RNS system even more effective in controlling seizures.
Jerzy Szaflarski, M.D., Ph.D., professor in the Department of Neurology and director of the UAB Epilepsy Center, says data from research studies dating back several years indicate that many patients will respond to the stimulation and have significant reduction in their seizures.
“This is not a treatment that will cure epilepsy,” he said. “This is a treatment that will help control seizures in a very specific group of patients who otherwise are not candidates for surgery. I don’t expect too many patients to become seizure-free; but if we can decrease their seizures by even half, we can make huge improvements in their lives.”
Conner agrees. She is working on a degree in elementary education and had episodes in the past in which she had a seizure while student-teaching. The reduction in seizures will give her more independence.
“I’ll be able to do more,” Conner said. “For instance, I’ll be able to drive. I’m 24, and I’ve never driven a car. The big hindrance with the seizures was that, when they hit, I couldn’t function and was unable to do anything. Now I simply feel this flash, and then it goes away without affecting my motor function.”
The RNS system is for patients who have severe seizures but do not respond to medications and are not candidates for surgery because the location of their seizure onset is at a sensitive part of the brain. It is also only for patients whose seizure onset can be traced to just one or two locations in the brain.
“We’re very excited to offer this therapy to our patients who are not candidates for more traditional therapies for epilepsy,” Szaflarski said. “We see multiple patients like that every year, and the RNS system could make a huge difference in the lives of those patients. There is already data to show that the quality of life of those patients has improved significantly with RNS.”
For more information on the RNS system, contact the UAB Epilepsy Center or make an appointment via the Kirklin Clinic at 205-801-8986.
Compliments of Bob Shephard
Changes in the eye might predict onset of frontotemporal dementia
The researchers studied a group of individuals who had a certain genetic mutation that is known to result in FTD. They discovered that, before any cognitive signs of dementia were present, these individuals showed a significant thinning of the retina compared with people who did not have the gene mutation.
“This finding suggests that the retina acts as a type of window to the brain,” said Erik Roberson, M.D., Ph.D., associate professor in the Department of Neurology at UAB and a study co-author.
Roberson and Timothy Kraft, Ph.D., associate professor in the UAB Department of Vision Sciences, collaborated with the lead investigators, Li Gan, Ph.D., from Gladstone and Ari Green, M.D., associate professor of neurology at UCSF.
“Retinal degeneration was detectable in mutation carriers prior to the onset of cognitive symptoms, establishing retinal thinning as one of the earliest observable signs of familial FTD,” Gan said. “This means that retinal thinning could be an easily measured outcome for clinical trials.”
Although it is located in the eye, the retina is made up of neurons with direct connections to the brain. This means that studying the retina is one of the easiest and most accessible ways to examine and track changes in neurons.
This electroretinogram image shows photoreceptor activity from two mice. The gray line represents the animal model that has frontotemporal dementia, the black line is the control or healthy mouse. The large negative spike in the diagram indicates a reduction of ganglion cells in the retina of the mouse model that mirrors human dementia.Roberson’s laboratory has been studying an animal model for FTD. Using a process called ERG, or electroretinogram — similar to an EKG — Roberson and Kraft showed that the retinas in mice with FTD had a loss of ganglion cell function; these cells are responsible for transmitting signals from eye to brain. That data, along with additional ERG studies that Kraft performed in California, aligned well with comparable human studies conducted by Gladstone and UCSF.
“We have a more complete understanding about how the retina functions as opposed to the operations of the complex brain,” said Kraft. “That makes it much easier to use the retina as a tool for better understanding FTD.”
The researchers also discovered new mechanisms by which cell death occurs in FTD. As with most complex neurological disorders, there are several changes in the brain that contribute to the development of FTD. In the inherited form researched in the current study, this includes a deficiency of the protein progranulin, which is tied to the mislocalization of another crucial protein, TDP-43, from the nucleus of the cell out to the cytoplasm.
However, the relationship between neurodegeneration, progranulin and TDP-43 was previously unclear. Using the UAB mouse model of FTD, the scientists were able to investigate this connection for the first time in neurons from the retina. They identified a depletion of TDP-43 from the cell nuclei before any signs of neurodegeneration occurred, signifying that this loss may be a direct cause of the cell death associated with FTD.
TDP-43 levels were shown to be regulated by a third cellular protein called Ran. By increasing expression of Ran, the researchers were able to elevate TDP-43 levels in the nucleus of progranulin-deficient neurons and prevent their death.
“The results of this study have shown that we can use the thinning of retinal cells as a marker for this type of dementia,” said Roberson. “Further studies may also help determine whether the changes in the retina can be utilized as a marker of disease progression. We may also be able to use the retina as a means of gauging the effectiveness of new therapies.”
Researchers from the University of Texas Southwestern also collaborated on this study. It was funded by the Consortium for Frontotemporal Dementia Research, Bluefield Project to Cure FTD, National Institutes of Health, UCSF Resource Allocation Program, UCSF Alzheimer’s Disease Research Center, Chartrand Foundation and Clinical & Science Translational Institute, Howard Hughes Medical Institute, Alzheimer’s Association, Welch Foundation, and Alzheimer’s Drug Discovery Foundation
By: Bob Shephard
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