West Virginia’s Battle Against Chronic Diseases
By Blair Dowler
Dr. Ali Rezai. Photo by WVU Medicine.
Around the world, countless people are affected by chronic pain and degenerative brain diseases like Alzheimer’s on a daily basis. In West Virginia, a world-class team of researchers, scientists and physicians from across the globe have come together at the West Virginia University (WVU) Rockefeller Neuroscience Institute (RNI) to investigate the causes of these crippling health problems and search for cures.
Under the direction of Dr. Ali Rezai, RNI’s director and a leading neurosurgeon, progress is being made in the battle for new treatments for these debilitating diagnoses. The recent phase II trial of a new treatment for early-stage Alzheimer’s and the launch of a clinical trial of a non-opioid micropellet implant for chronic pain are just two examples of how Rezai and his team are creating hope not only for West Virginians but people suffering all around the world.
Promising Progress Against Alzheimer’s
According to the Alzheimer’s Association, more than 5 million Americans are living with Alzheimer’s disease, 37,000 of which are West Virginians. That number continues to grow every day at a terrifying rate—it is estimated that someone is diagnosed with Alzheimer’s every 60 seconds.
“Despite these staggering numbers, sadly there is no cure,” says Rezai. “And despite more than 500 clinical trials and billions of dollars spent, there have been no effective treatments. Many other drugs and efforts have failed, and as a result, we need to explore all possible opportunities for new technologies.”
One of those opportunities came in the form of a phase II trial for an Alzheimer’s treatment that uses a new form of technology provided by INSIGHTEC, an Israeli medical device company. The new treatment, which involves an incisionless surgery that does not require pharmaceuticals, uses focused ultrasound treatment to disrupt the blood-brain barrier in regions of the brain like the hippocampus that are directly affected by this degenerative disease.
Phase I of this trial took place at Sunnybrook Health Sciences Centre in Toronto, where the center’s team was able to reversibly open the blood-brain barrier in Alzheimer’s patients. According to WVUMedicine.org, the blood-brain barrier, which separates the bloodstream from the brain tissue, limits many potentially effective medicines and the immune system from reaching diseased areas of the brain.
During the phase II trial, which took place at RNI in October 2018 and was led by Rezai, microscopic bubbles were injected into the patient’s bloodstream, and when those bubbles were exposed to focused ultrasound waves, the blood-brain barrier located in the area targeted by those waves was temporarily opened. The RNI team targeted the memory and cognitive brain centers that are commonly impacted by the plaques found in Alzheimer’s patients. This was the first procedure of its kind in the world.
Judi, a 61-year-old nurse who has been an educator in Morgantown’s neonatal nursing community for several years, was the first patient in this trial. Due to her early-stage Alzheimer’s and the resulting short-term memory loss, she had to stop working.
During the three-hour procedure, the team successfully accomplished the goal of opening up the blood-brain barrier to reach the area affected by Alzheimer’s. Going forward, the team will monitor and evaluate whether focused ultrasound reduces the debilitating plaques and cognitive decline that are the hallmarks of Alzheimer’s. This is a clinical trial, so while Rezai is hopeful for positive outcomes, it is still too early to tell what the end result will be. Based on previous work and what is being seen, though, the team is optimistic that this new technology will allow a unique, non-invasive way of opening the blood-brain barrier and activating the brain’s immune system.
INSIGHTEC selected RNI as the first site for the trial because of its world-class team and its infrastructure for finding solutions and rapid cycle innovation. The institute brings together teams of industry and academia with a strong focus on rapidly developing new ways to diagnose, monitor, manage and treat some of the key disorders facing humanity.
With this being the first patient in the world to receive this treatment, WVU Medicine is setting the stage for the state to be considered a leader in the medical and technological fields. The procedure required more than 50 specialists—including engineers, physicists, neurologists, psychiatrists, neurosurgeons, industry leaders, MRI and imaging specialists and nursing staff—to come together for this trial.
“We are pleased West Virginia University was chosen as the first site in the world to do this trial,” says Rezai. “We have a unique culture here, which allows us to do many firsts in the world in an agile fashion, but it’s not just about being the first. It’s about accelerating the path for discovery and innovation and deploying technologies together to help tackle some of the big problems.”
Encouraging Alternatives for Chronic Pain
Like the astounding number of people who are facing Alzheimer’s, chronic pain and addiction have also come to be major issues, which has led to another major problem West Virginia is facing: the opioid crisis. West Virginia, per capita, has the highest overdose mortality rate in the nation with the surrounding states of Ohio and Pennsylvania trailing close behind.
“It is a big, big problem—much more than at the peak of the AIDs crisis or the number of car accidents,” says Rezai. “West Virginia is at the forefront of the opioid crisis, and we want to be at the forefront of the innovation and technology to help it and prevent it.”
Through a clinical trial that tests the effectiveness of an injectable non-opioid, non-steroid micropellet to treat sciatica, RNI is positioning itself to fill that role.
In November 2018, RNI successfully enrolled and treated the first patient in a phase III clinical trial that tests how effective an injectable non-opioid, non-steroid micropellet can be in treating sciatica. In the procedure, a clonidine micropellet half the size of a grain of rice was inserted into the patient’s lower back, where it will remain for up to one year. Historically, clonidine has been used to treat pain and high blood pressure.
“Even though West Virginia is leading the nation in overdose deaths, it is now taking the lead in helping find an answer for this epidemic by being the first in the world to launch this phase III clinical trial,” says Rezai. “If the study is successful, instead of taking opioids for chronic pain, patients would be able to get an injectable pellet that dissolves over time and treats their pain. Phase I and II have been promising, so now we are doing this next phase trial with the FDA and the company Sollis Therapeutics.”
The principal investigator for the micropellet trial is Dr. Richard Vaglienti, the director of the WVU Medicine Center for Integrative Pain Management. He says a major way to prevent opioid misuse is to minimize the number of opioids that are prescribed.
“There is a group of people that is already addicted to opioids, and that is a single problem in and of itself,” says Vaglienti. “Then there’s a second group that is made up of those individuals who have chronic pain that prior to now would have gone on to use chronic opioids, and now we’re developing a bunch of other treatment processes to prevent that group from transitioning into the dependent group. So, we have a two-prong mission we’re on.”
Sciatica, which is leg and back pain caused by irritation of the spinal nerves due to aging, sports, job-related activities or traumatic events, is a condition affecting millions of Americans each year. When other forms of treatment like physical therapy, home remedies and other prescriptions don’t work, opioids may be prescribed to manage the pain. In fact, according to Rezai, studies have shown that 60 percent of patients with back pain are treated with opioids.
While opioids are effective for pain control, they are also highly addictive. This is because the brain changes fundamentally with opioid use. If a patient takes opioids after a procedure or surgery for pain, after just one day of use the chances of that patient continuing to take them one year later is 6 percent. If that patient takes them for a month, that percentage increases to 30.
Vaglienti is optimistic about the studies and trials taking place at WVU and RNI, and he hopes these will open the door to studies for other types of disease like diabetic neuropathy, chemotherapy-induced neuropathy and other instances in which, prior to their work, opioids were the only source of relief. He wants West Virginians to know there are a lot of people working on their behalf to address a lot of different medical problems, and it’s his team’s goal to provide the highest quality research and care possible.
As for Rezai, he is excited about the future of medicine in Morgantown and West Virginia as a whole.
“From my perspective, it’s an exciting time to be in West Virginia,” says Rezai. “There are a lot of opportunities for technology development and innovation and ways we can find solutions for people with chronic diseases. West Virginia, in my opinion, is where the future of medicine is going to take place. We need to continue to deploy resources, explore and bring new jobs and technologies to the area. The future is definitely bright for West Virginia, and what we’re doing here is going to help people in the state, the surrounding states and the country.”
