Carly's Law patients start receiving marijuana-derived CBD oil to treat seizuresAlabama's first two patients in the state-approved Carly's Law study conducted by the University of Alabama at Birmingham last week began taking an experimental marijuana-derived medication for treating severe seizures.
A pediatric patient received the first dosage of cannabidiol, also known as CBD, on April 1 and the first adult patient started the treatment last Thursday through the study, said Dr. Jerzy P. Szaflarski, a neurology professor and director of the UAB Epilepsy Center.
"Both of these patients have what we call catastrophic epilepsy, which is a very difficult-to-control epilepsy," Szaflarski said in an interview, noting the patients each have at least 100 seizures a month and both have "failed almost all treatments including brain surgeries."
Szaflarski, who is the principal investigator of the adult study, said another patient could start receiving the treatment on Thursday and at least another two could begin next week. "If all goes well, by the end of the month we will have at least 10 patients in the study," he said.
With the medication, officials hope to see "some improvement in both seizure control and quality of life" for the patients, he said.
UAB's study -- one of the largest in the nation -- will examine the effects of the CBD medication delivered in oil form orally to patients. Although the medication comes from marijuana, it does not create the intoxicating properties associated with the drug.
Authorized by the Alabama Legislature last year, the study known as Carly's Law gets its name from the 4-year-old daughter of the Birmingham area's Dustin and Amy Chandler. The Chandlers have been pushing to allow the study that could potentially benefit children and adults suffering from seizures, including their daughter who has a rare genetic disorder called CDKL5.
"To me, it's a relief to know that we've finally begun and all the hard work is literally paying off for these patients," Dustin Chandler said in an interview today, noting his daughter is not one of the patients already accepted into the study.
"It's a relief knowing finally these people who have been suffering and bound to such a life -- they can't live the life they want because of epilepsy and debilitating seizures -- can finally get some relief. We all understand from day one it's not going to work for everybody ... but just to know it's now being dispensed and prescribed, it's just a relief," Chandler said.
The medication's delivery is happening after UAB received approval from the U.S. Food and Drug Administration on March 2 that allowed the institution to officially begin the study, which will include 50 children and 50 adults.
Szaflarski said medical officials associated with the Carly's Law studies have been contacting patients as their completed application packets arrive and undergo review. "We had initially at least around 400 phone calls from people who are interested" with more than 350 packets mailed to prospective patients, he said.
UAB officials have received around 90 packets that are being reviewed. "We already have enough patients to keep us busy for a while," he said, noting that among those received, "approximately 60 to 70 percent are pediatric and about 30 to 40 percent are adults."
Patients take the CBD oil twice a day while UAB officials monitor them for signs of progress. Patients come in for visits every two weeks, at which time doctors can prescribe an increased dosage.
Szaflarski said the study will monitor patients using CBD for side effects as well as interactions with other medications. "We will give patients one more opportunity, one more option to have their seizures under better control and in the end hopefully a better quality of life," he said.
GW Pharmaceuticals is providing the medication free of cost for the 100 patients in the study. UAB could approach the company to request more medication if the demand is greater.
"We don't anticipate any issues for the next few months," Szaflarski said about reaching the study's cap. "We do have an open option at the end of enrollment that we can go back to the company and ask them if they are willing to supply more. ... If it is clear we will exceed the number for 100, we will definitely go
By Martin J. Reed | firstname.lastname@example.org | Follow on Twitter on April 08, 2015 at 4:42 PM, updated April 08, 2015 at 4:50 PM
Searching for a Cure
Photo courtesy of Mary T Miller.
Parkinson’s disease impacts an estimated one million people in the United States, according to the National Parkinson Foundation.
Local residents are working hard to raise awareness and research the disease. The Parkinson Association of Alabama (PAA) recently named Vestavia Hills resident Mary T. Miller as its executive director. The organization works closely with UAB, where local resident David Standaert is the chair of the neurology department.
Parkinson’s disease is defined as a progressive neurological disorder associated with a loss of dopamine-generating cells in the brain. Dopamine is a chemical that sends messages to the part of the brain that controls movement and coordination. As Parkinson’s progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.
There are also many more non-motor symptoms. The four key motor symptoms of Parkinson’s disease are tremor of the hands, arms, legs or jaw; muscle rigidity or stiffness of the limbs and trunk; slowness of movement; and postural instability.
Other common symptoms include dementia or confusion, fatigue, sleep disturbances, depression and anxiety. All of these symptoms can vary from person to person.
Founded in 1978, PAA is a local nonprofit organization committed to providing support, encouraging action, increasing awareness, and supporting research to lead to new and improved treatments for Parkinson’s disease.
PAA is the only organization that represents all Parkinson’s patients in the state, and the board of directors remains current on the latest legislative and research information.
Miller worked for 10 years for Cumberland School of Law at Samford University, where she was the director of alumni.
She is excited to combine her passion, skills and experience to help the foundation through various research and fundraising activities.
“My main goal is to increase awareness of who we are and what we are doing,” said Miller. “We work a lot with the UAB neurology department. They are leaders in research of Parkinson’s disease.”
Standaert explains the biggest misconceptions surrounding the disease.
“The most common myth is that there is no treatment,” said Standaert. “This simply isn’t true. We have a number of excellent treatments that can greatly improve the symptoms and restore a good quality of life for many years. Most of these medications are based on replacing the missing dopamine through one means or another. There are also important effects of non-medication treatments, especially exercise. What we don’t have is a cure for Parkinson’s — which is the focus of much of our laboratory work.”
Standaert explains that UAB had a very important role in two new treatments for the disease, which were approved at the beginning of the year: a pill called Rytary and an infusion pump system called Duopa.
“Both of these are better ways of delivering dopamine therapies, and important parts of the studies were done at UAB,” he said. “More upstream, we are working hard on new approaches to slow the disease progression. One of the exciting new ideas is that the immune system may have an important role, and just this month we have received a major new grant award from the NIH to explore how this could lead to better treatment.”
Standaert shares his advice for those who have a loved one battling the disease.
“It is important to remember that Parkinson’s disease affects the whole family, and both the patient and caregivers need support,” he said. “We do recommend that patients visit a movement disorder specialist at least twice a year to ensure that the diagnosis is accurate and the treatment is the best possible. Families should take advantage of the many support groups in the state.”
On April 23, PAA will host their signature event, Taste for a Cure, at Old Car Heaven. Proceeds will help fund research as doctors search for a cure for the disease.
For more or to purchase tickets, visit parkinsonalabama.com.
If you would like to help sponsor the event or have questions please contact Miller at.
By Katie Turpen
Lorenz, Nicholas honored for excellence in teachingTwelve faculty, including two from the UAB School of Medicine, were honored with the President’s Award for Excellence in Teaching during the annual Faculty Awards Convocation on March 18 in the UAB National Alumni Society House.
Robin Lorenz, M.D., Ph.D., professor of Pathology and assistant dean for Physician-Scientist Education, and Anthony Nicholas, M.D., Ph.D., professor of Neurology, were among the honorees. The President’s Award for Excellence in Teaching recognizes full-time regular UAB faculty members who have demonstrated exceptional accomplishments in teaching. A recipient is chosen from the College of Arts and Sciences and each of the schools and the Joint Health Sciences.
Anthony Nicholas, M.D., Ph.D. “This is a tremendous recognition for Drs. Lorenz and Nicholas’ contributions to being not only great teachers, but great educators,” said Selwyn M. Vickers, M.D., F.A.C.S., senior vice president for Medicine and dean of the UAB School of Medicine. “Their peers recognize their commitment, dedication and excellence in conveying knowledge to their students and their peers.”
Nicholas studied at UAB before joining the faculty in 1996. In his nearly 19 years here, Nicholas has delivered more than 700 formal lectures and presentations on more than 40 different topics. He embraces new technologies, including webcasts and his YouTube channel. The five-video series on how to properly perform and document the neurological exam has been viewed more than 35,000 times since 2012, and they now are prerequisite viewing for all third-year medical students starting the neurology clerkship at all four UAB campuses.
“Tony is a highly regarded lecturer and small-group facilitator,” said Craig Hoesley, M.D., professor of Medicine. “He is a highly engaged and enthusiastic educator who designs and implements his materials in a detail-oriented and thought-provoking manner.”
Robin Lorenz, M.D., Ph.D.Lorenz joined UAB in 2002 and has since been recognized for teaching and mentorship. During her tenure as associate director of the Laboratory Medicine Residency Training Program (2002-08), Lorenz helped to develop a set of “Laboratory Medicine Resident’s Survival Manuals,” which continue to be updated and distributed to incoming pathology residents. Her colleagues say she is most well-known at UAB for her leadership of the Medical Scientist Training Program. She has designed and implemented systemic changes in the MSTP curriculum and extracurricular activities that strengthen the program. Her successful leadership of the program led her to be named assistant dean for physician scientist education, which enables her to build other physician-scientist pipeline programs.
“Robin has outstanding accomplishments in teaching as demonstrated by her involvement in multiple programs that impact physician and scientist training, as well as helping to increase the pipeline into these graduate and medical education programs,” said Jay McDonald, M.D., professor emeritus of Pathology. “She inspires students through her own research and clinical activities and also through her excitement for and love of academic medicine.”
See the full article on the President’s Award for Excellence in Teaching recipients campus-wide from the UAB Reporter.
Mind the gap: Probing the brain-machine interface
Mind the gap: Probing the brain-machine interface
March 20, 2015
By Jeff Hansen
Experts from around the country gathered at UAB to discuss breakthroughs in linking thought with actions through technology.
On the ceiling of the Sistine Chapel, God reaches out to touch Adam. The eye locks on the small gap between their index fingers, a slice of space dividing the ethereal from man.
A similar gap challenges researchers who work with paralyzed or handicapped patients — how to synch the human brain with a machine or computer.
Surprising breakthroughs from decades of basic science were featured at the recent, all-day 2015 Bevill Neuroscience Symposium — “Brain-Machine Interfaces” at UAB, which drew 200 attendees.
The most vivid example was Jan Scheuermann, a quadriplegic from Pittsburgh. Surgeons cut through her skull in 2012 to place two 96-electrode grids on the surface of her brain. Each electrode, about the size of a pea, penetrates 1/16 inch into the brain to detect electrical signals from individual neurons. Those signals go to a decoder outside her body. The decoder translates nerve firings into commands that move a robot arm as Jan merely thinks of moving her own, paralyzed arm.
Jan Scheuermann. Photo credit: University of Pittsburgh Medical Center
Under command of that small spot on Jan’s cortex, the machine hums into action, picking up an object in its robot hand and moving it to a shelf or table.
At first the researchers kept the arm across the room, worried that Jan might inadvertently punch herself. As Jan gained skill, the University of Pittsburgh researchers brought the arm near Jan’s side to let the paralyzed woman fulfill her greatest wish.
In meet. Neuroprosthetics like Jan’s robot arm can overcome the loss of movement. As UAB College of Arts and Sciences Dean Robert E. Palazzo, Ph.D., has explained, outside signals can also be sent into the brain. “The promise for the development of integrated portable devices that can overcome loss of hearing … and possibly even loss of sight is upon us.”
UAB’s Mark Bolding, Ph.D., mentioned even broader potentials.
The ability to feed signals back into the brain could allow someone like Jan to have proprioreception (the sense of how our bodies are positioned) or haptics (tactile sensation) from her robot arm. It could create social and affective prosthetics that create automated recognition of faces or expressions. It could be used to manage pain and modulate awareness. It could even create completely new senses — such as the ability to detect sonar, infrared light or magnetic fields, in effect allowing us to navigate like a bat, see like a bee or migrate like a bird.
“The mind-machine interface is the future of human neuroscience, using technology to overcome injury and disease of the nervous system, and at the same time providing a window into how the brain works.” — David G. Standaert, M.D., Ph.D., John N. Whitaker Professor and chair, UAB Department of Neurology
Here are overviews of the Bevill symposium talks:
- Andrew Schwartz, Ph.D., University of Pittsburgh, the speaker who showed the Jan Scheuermann video, explained the decades of science that led to her remarkable neuroprosthesis. “When you move your hand and arm, you see the whole brain light up in a complex pattern,” he said. The breakthrough came by watching the firing rate of a single neuron as a monkey moved its hand along a two-dimensional, virtual plane. “We saw that one neuron fires as the hand goes up and is silent when the hand goes down. There is an ordered relation between the rate of neuron firing and the direction of motion.”
Different neurons, it turned out, had firing rates that related to different directions. Moreover, the firing rate of each single neuron could be written as a vector dot product and those dot products could be summed into a population vector, which in neuroscience is the sum of the preferred weighted directions of a population of neurons.
The final equation to control the arm had to include three dimensions for the x, y and z axes, one aperture dimension to open and close the robot hand, three dimensions for the yaw, pitch and roll of the wrist, and four more controls that could produce 80 percent of a person’s hand shapes.
Schwartz also showed a “60 Minutes” interview with Scheuermann, where she ended the interview with a robot-arm fist bump with the CBS reporter.
In response to questions after his talk, Schwartz said there is active research on ways to activate the sensory cortex, that the neuron signals from the electrode grids tended to degrade from about 6 months to 2 years, and that figuring out how to vary force of the grip or the arm is an important topic of research.
- Leigh R. Hochberg, M.D., Ph.D., Brown University, Massachusetts General Hospital, Harvard Medical School, described the BrainGate2 Pilot Trial that also uses a small array of electrodes the size of a baby aspirin, placed on the surface of the brain.
BrainGate has 5.4 years of cumulative experience with nine people. Hochberg showed a video of one woman, 15 years after her paralyzing stroke, reaching out with a robot arm to give herself a sip of cinnamon latte.
Hochberg noted that all the recent advances and efforts — such as helping a “locked in” patient control typing or compose computer speech, controlling a prosthetic arm, reconnecting the brain with the body’s own neuromuscular system, or rehabilitating and repairing neural networks — have been built on 50 years of fundamental, publicly and philanthropically funded science. He also said that progress requires an interdisciplinary team of neurologists, neuroscientists, engineers, computer scientists, neurosurgeons, mathematicians and others.
He also mentioned potential applications of deep brain stimulation (DBS) for obsessive compulsive disorder (OCD); bipolar disorders; or to understand, predict, warn or suppress epilepsy.
- P. Hunter Peckham, Ph.D., Case Western Reserve University, described implantable neural prostheses — a different approach to restorative therapy for paralyzing central nervous system disorders.
Sensors implanted under the skin near muscles that the patient can still control, such as in the shoulder or neck, pick up signals from the nerves. These go to a control device that then sends signals via other surgically implanted wires to electrodes surgically placed on the muscles of the paralyzed arms and hands. In effect, the patient’s own muscles become rewired.Peckham showed a video of a woman with a C6ASIA A spinal cord injury. Thanks to her implanted neural prosthesis, she could pick up a hair drier with two hands and blow her hair, and then brush her head with a hairbrush. Other areas in need of this kind of control are breathing (especially, to create a stronger cough), using the bladder and bowel, reaching and grasping, supporting the trunk, and standing or walking
Between 1986 and 2001, 220 spinal cord injury patients received generation 1 implants, Peckham said. Twenty patients have received the multichannel generation 2 implants that allow two simultaneous types of control, such as hand and bladder, hand and trunk, hand and standing system, or bilateral hands. Peckham said that patients will begin to get fully implantable, generation 3 neural prostheses this spring.
- Adrienne Lahti, M.D., UAB, suggested that the brain-machine interface might offer future therapies for schizophrenia.
Schizophrenia affects about 1 percent of the world’s population. While psychoses can be treated with drugs — which have side effects and require weekly blood draws — there are no treatments for cognitive and negative symptoms.
There are now multiple reports of functional connectivity abnormalities in schizophrenia, Lahti said, where the coherence between brain regions is diminished. Also, post-mortem studies of the hippocampus of schizophrenia patients show altered GABA interneurons. Furthermore, in people with OCD, deep brain stimulation of the brain’s nucleus accumbens has been shown to improve the brain’s frontostriatal functional connectivity and decrease the symptoms of OCD.
These three lines of evidence suggest a thought experiment for schizophrenia, Lahti said. Namely, can we restore connectivity, and how? The hippocampus could be a possible target in this approach.
- Mark Bolding, Ph.D., UAB, described brain neuro-modulation using transcranial focused ultrasound.
This high-intensity focused ultrasound is administered from outside the skull, and it can be guided with an MRI, Bolding, said. It offers high resolution (1 to 3 mm3) and is non-invasive. The ultrasound can target specific areas with variable intensities that can either heat or ablate that small part of the brain.
Focal ablation can be an outpatient procedure to treat essential tremor. Low-power ultrasound can modulate neuron firing, up or down. Local neuro-modulation is being tested in an epilepsy model.
The transcranial ultrasound can be used to give feedback from motor system prosthetics, or it can be used in functional mapping of the brain, as a complement to fMRI. The ultrasound can stimulate induced function or temporarily interrupt activity, Bolding said. It can help determine causality in networks, and the introduction of iron oxide nanoparticles that are ruptured by ultrasound provides a contrast agent for MRI.
“Transcranial focused ultrasound has a lot of future here at UAB,” Bolding said.
- Harrison Walker, M.D., UAB, said that more than 150,000 patients worldwide have received deep brain stimulators. He showed a video from a UAB surgery to show how nerve recordings during an operation to implant a pulse generator helped determine the best location for the pulses.
U.S. Food and Drug Administration-approved targets for deep brain stimulation are Parkinson’s disease, generalized dystonia, essential tremor and refractory OCD. Walker and UAB patient Bennie Burton also showed the audience how Burton’s Parkinson’s tremors return when Walker temporarily turns off his deep brain stimulation (for an example, see this 2013 UAB video of Burton).
Deep brain stimulation might help in depression, Walker said, but doctors cannot see an immediate effect like they do with conscious movement disorder patients during surgery, making it harder to know where to place the electrodes.
- Other UAB speakers were Rajesh Kana, Ph.D., who talked of recent research to distinguish autism participants from control volunteers through multimodal neuroimaging; and Corey Shum, who described the use of virtual reality to simulate combat casualty care for U.S. Air Force Pararescue medics.
Amie McLain, M.D., UAB, the kickoff speaker, set the stage for the symposium by describing over a century of progress in putting a person’s life back together after incapacitating injury or disease. “We have now reached the technical age of rehabilitation enhancement,” McLain said. “With brain plasticity, we get the patient to do something to create new pathways in the brain, and this involves real recuperation of the brain … One of the biggest challenges now is the brain-machine interface, or the brain-computer interface.”
Such brain-machine interface research is inherently interdisciplinary and will require a different type of funding than the traditional NIH RO1 grants, Palazzo said. He noted that the issue of design —another interdisciplinary area — kept coming up in the talks.
“So, what can we do here at UAB?” he asked the participants. “We have some areas of strength already. We need to identify the gaps and identify areas where we might contribute.”
“Finally,” Palazzo said, “we will need to identify partners — other researchers, corporate partners, federal agencies and philanthropic partners. Progress can be made, but probably not by just one department, not by just one school, and probably not by just one university.”
The 2015 Bevill Neuroscience Symposium: Brain-Machine Interfaces
- Met on Feb. 27, at the UAB Alumni House.
- Honors former U.S. Congressman Tom Bevill, through the support of the Bevill Family Foundation and members of the Bevill family.
- Was presented by the UAB Comprehensive Neuroscience Center, the Department of Neurology in the School of Medicine, the College of Arts and Sciences and the School of Engineering.
- Ultimate goal of the Bevill Symposium in Neuroscience is to further our understanding of brain disorders and to develop new, improved treatments and cures.
- Leigh R. Hochberg, M.D., Ph.D., associate professor, School of Engineering and the Institute for Brain Science, Brown University; vascular and critical care neurologist at Massachusetts General Hospital; and senior lecturer on neurology at Harvard Medical School.
- P. Hunter Peckham, Ph.D., Donnell Institute Professor and director of the Functional Electrical Stimulation Center, Department of Biomedical Engineering, Case Western Reserve University.
- Andrew Schwartz, Ph.D., professor of Neurobiology, University of Pittsburgh.
- Mark Bolding, Ph.D., assistant professor, Division of Advanced Medical Imaging Research, Department of Radiology
- Rajesh Kana, Ph.D., associate professor, Department of Psychology.
- Adrienne Lahti, M.D., the Patrick H. Linton Professor and director of the Division of Behavioral Neurobiology, Department of Psychiatry
- Amie McLain, M.D., chair and professor, Department of Physical Medicine and Rehabilitation
- Corey Shum, technical director, Enabling Technology Laboratory, School of Engineering
- Harrison Walker, M.D., associate professor and medical director for surgical movement disorders, Department of Neurology