When scientists in Dr. George Vande Woude’s lab at the National Cancer Institute discovered the MET gene in 1984, they knew antibodies to MET would be valuable for diagnosing MET-positive tumors.
Years later at Van Andel Institute, Vande Woude and his colleagues were successful in generating MET4, an antibody with a high affinity for detecting MET in cells and tissues. Now the MET4 antibody is being licensed to Dako, a Danish-based worldwide supplier of cancer diagnostic tools. Dako will manufacture and distribute diagnostics that use the MET4 antibody developed in Grand Rapids.
Vande Woude describes the MET gene as a receptor that sits on the cell surface and transports crucial information into the cell. Normally, it is involved in important functions like wound repair and liver regeneration, but when it becomes abnormal, it promotes the spreading of cancer cells. MET4 antibody can find those cancerous tumors by finding where MET is located aberrantly.
“This is one of the best ways to determine whether abnormal MET is present in the tumor,” said Vande Woude, who is the founding director of VAI. He explained that if MET is found, doctors can use one of many drugs being developed by the pharmaceutical industry to target and treat the cancer by inhibiting MET activity.
“If we know MET is there, we can use the anti-MET drugs, as well,” he said. Early research has shown dramatic results in prostate, lung and gastric cancers.
“For generations, the medical community has focused on the tissue of origin for treatment, but with this new approach, the same gene can be involved in many different cancers and we can specifically target that abnormal gene,” said Vande Woude. “This is a great step forward in treating cancer.”
Strong growth over the last five years in understanding “cancer” genes like MET has helped; during this period, vast numbers of other cancer targets have been identified, and Vande Woude expects that using combinations of drugs against multiple cancer gene targets will hit home runs.
“We can truly state that the future is promising for cancer patients, and this is good news,” he said. “Many of the tumors where MET is involved are the most aggressive and many have no therapies. But with MET drugs, we now have potential new drug therapies for these diseases. This is good news for treating many different cancers. For cancers that have no other treatments, MET drugs can be important new tools in the doctor’s tool chest.”
Dr. John Keller
Small robot equals big strides
Imagine a Red Bull can sitting atop your spine and directing doctors where to put the screws and rods needed to stabilize your backbone.
That’s about the size of the Renaissance Robot that Metro Health surgeons are using to facilitate placement of the hardware used in spine surgeries.
For Dr. John Keller, the small robot has revolutionized how he does spine surgeries.
“We used to use bone matter along the spine and bracing on the outside. Then we moved to screws and rods to brace the spine. We would put them in based on landmarks of spine anatomy, but also getting X-ray pictures of the spine,” said Keller. “But in trying to place the screws more accurately, we came up with this new technology.”
The Renaissance Robot cuts down on the number of X-rays needed before and during surgery — from a minimum of 15 to two.
“The robot lines up where you should put that screw so it holds tight and so it avoids vital structures such as nerves and blood vessels. It’s perfecting the placement of the screws for the pinning of the vertebra,” said Keller. “It’s also a benefit to staff and doctors because they are exposed to less radiation.”
The robot looks like a soda can with arms that hook on the back of the spine, he explained. Its computer syncs a pre-surgery CT scan with two during-surgery X-rays and puts together a model.
The computer points to where the robot should move and where to put the incision. It also shows doctors the exact trajectory needed for best placement of the screws. This accuracy helps prevent follow-up surgeries, and even allows for the option of minimally invasive spine surgeries.
“In some cases we’re putting screws through the skin, using small incisions to place the screws from outside,” said Keller. “This is beneficial because the robot helps place the screws very accurately in a minimally invasive surgery.”
Metro Health is one of fewer than a dozen hospitals around the country using the Renaissance Robot. “It allows a doctor to operate with more confidence, safety and accuracy,” said Keller.
Adejoke Ayoola, Ph.D., R.N.
Nursing professor receives grant
Adejoke Ayoola, Ph.D., R.N., has a heart for women who struggle with understanding their bodies and reproductive choices. This assistant professor of nursing at Calvin College is taking that concern into three Grand Rapids neighborhoods, thanks to a $350,000 grant.
Ayoola received the grant from the Robert Wood Johnson Foundation’s Nurse Faculty Scholars program. She will use the funds to examine the effectiveness of the “Preconception Reproductive Knowledge Promotion” intervention protocol, designed to promote reproductive health and positive pregnancy outcomes in racially diverse, low-income neighborhoods.
She’ll study 120 women between the ages of 18 and 44 in the Creston/Belknap, Baxter/Madison and Burton Heights neighborhoods, with help from Calvin College nursing students, research assistants and health care professionals who already are working in those neighborhoods. Recruitment of women began in October, with interventions beginning in February 2013.
“We will teach them about nutrition, being healthy, how to know their ovulation times, and about reproductive health. And we’ll visit these women in their homes every month,” said Ayoola.
“Our ultimate goal is for women to know more about their bodies, and when they know about their bodies — when they can get pregnant — they’ll use birth control to prevent an unplanned pregnancy,” she said. “If they don’t use birth control and get pregnant, they’ll recognize the pregnancy early and start prenatal care and hopefully stop bad behaviors such as smoking and drinking alcohol.”
Interest in the PREKNOP research came in part from the women themselves. Calvin College’s nursing students have been working in the neighborhoods for years and have fielded many requests for this type of information. Ayoola said they consistently have asked for help in knowing their reproductive systems better so they can better plan pregnancies.
“My supposition is that the women will learn that they can control their reproduction; they will know when they are at risk of pregnancy and will make informed decisions about birth control and perhaps become consistent users of birth control,” said Ayoola.
The grant will allow Ayoola to reduce her teaching hours at Calvin College, pay for research materials and research assistant salaries, and pay for gift cards given to study participants. The first six months of the three-year grant is for administrative details and recruitment of women, then two years of research, and finally six months to write up the findings.
Ayoola came to the United States from Nigeria in 2003 to complete her doctorate at Michigan State University. She finished her degree in 2007 and moved immediately to Grand Rapids to teach at Calvin College.
Dr. Gregory Golladay
Nanosensors fine-tune knee surgeries
There are about 600,000 knee replacement surgeries done in the United States each year, and that number is growing as our population ages. Though knee replacement is highly successful, about 1 percent each year will require follow-up surgery (called a revision), and about two-thirds of revisions are necessary within the first 3.5 years. About one in four revisions is done because the knee feels unsteady when walking down steps or on uneven ground. Another group needs the surgery because the joint feels too tight and is stiff.
The problem, according to Dr. Gregory Golladay of Orthopaedic Associates of Michigan, is the subjective nature of the surgeries, as surgeons use touch-and-feel to determine how tight or loose the joint replacement should be.
The solution may be new nanosensors being tested by Dr. Golladay that allow surgeons to see exactly where the pressure points are and how the knee is moving. The nanosensors are embedded in a trial implant to determine exactly how the actual implant should be placed.
“The nanosensors were developed to assess tension and to show surgeons graphically how the knee is moving and where the peak pressure is,” he said. “The nanosensors show a quantified amount of pressure on the inside and outside of the knee.”
Dr. Golladay is one of 20 surgeons in the U.S. participating in the nanosensor trial over the last year. He’s been enrolling patients for more than six months and has done more than 20 of the 50 required knee replacements to complete the test.
“Of the patients we’ve studied, almost half have reported at six weeks that their knee feels normal. This is remarkable because most knee replacement patients don’t reach maximum improvement until about 12-18 months out,” he said. “The data at six months also looks highly favorable.”
Dr. Golladay, who does 400 to 500 hip and knee replacements each year, has been at Orthopaedic Associates and its affiliate Spectrum Health since 2004. He is the clinical advisor for joint replacement at Spectrum.
He sees huge benefits from the use of the tiny sensors.
“The idea is that we would decrease the number of revisions. These revisions are a huge disappointment to the patient, are costly and inconvenient, and carry risk. This would improve outcomes and patient satisfaction, and the reduction in revisions will decrease our health care costs,” said Golladay.
He also envisions new uses for the nanosensors, which are currently disposable — used only during the procedure and then removed. He forecasts embedding the sensors into the implant, then monitoring the implant over time for wear, instability and premature failure.
“It’s not a leap of faith to think that patients could use an application on their smartphones, or call in like pacemaker patients do, to get their knee implant checked. It would improve convenience and cost of monitoring,” Golladay said.
Dr. Philip Gorelick
Bat venom for stroke victims
The enzyme desmoteplase, which prevents blood from clotting, occurs naturally in bats. That ability to suck blood indefinitely — the stuff of legend and nightmare — transfers handily into the medical field, thanks to researchers who saw the possibilities for victims of stroke.
Dr. Philip Gorelick, medical director of Hauenstein Neuroscience Center at Saint Mary’s Health Care, is leading a national study at top stroke centers to look into the clot-busting (thrombolytic) properties of desmoteplase and how it may be used to offer stroke victims new hope.
“Bats live, in part, on blood, so in order for them to get blood into their system without clotting, they have to have a substance in their system to prevent clotting,” said Gorelick, who is co-lead on the study with vascular neurologist Dr. Muhammad Farooq, also at Saint Mary’s.
Desmoteplase, now made synthetically, has special properties that make it go after clots, and has a special affinity for breaking up clots in brain arteries.
The current treatment for ischemic stroke (stroke cause by a blood clot) is t-PA, tissue plasminogen activator, which must be administered within 4.5 hours of the initial stroke event.
“T-PA is limited in that we have only 4.5 hours to administer it, and a side effect is bleeding. But now we have a better drug: We’re testing desmoteplase for use up to nine hours after stroke, and it doesn’t appear to have the neurotoxicity of t-PA,” said Gorelick. “Prolonging that window would be very welcome.”
Desmoteplase trials are going on in Europe and the United States. The European trial, called DIAS 3, will probably produce results in nine to 12 months. The U.S. trial, DIAS 4, will take longer because the study is only about half completed. However, Gorelick said the FDA may consider moving to accept the drug faster if the DIAS 3 trial is strongly positive.
“T-PA is only being used in about 3 to 5 percent of stroke cases, but almost 800,000 people in the U.S. have a stroke every year. Many get to medical care beyond the 4.5 hour window for t-PA,” said Gorelick. “We need better ways to treat these patients. If desmoteplase becomes available, 20 to 40 percent of all stroke victims would be eligible for the treatment.”
He calls the treatment “practical and promising.” It requires only a CT scan of the brain and arteries and is delivered intravenously.
“I’m eagerly waiting to see what will come back from the trial. I think there’s a very, very good chance the tests will come back positive,” Gorelick said.
Dr. Patrik Brundin
Rethinking Parkinson’s disease
A paradigm shift is underway in how doctors view Parkinson’s disease. In the past, doctors had no idea how the disease was triggered in the human body. Now, researchers such as Dr. Patrik Brundin at Van Andel Research Institute think that a misfolded protein, which can trigger disease at the cell level, moves from an unhealthy cell to a healthy one, infecting those cells and creating the symptoms of Parkinson’s.
Brundin, who moved to Grand Rapids from Sweden this past January, also hypothesizes that perhaps Parkinson’s disease doesn’t start in the part of the brain it most affects, but instead may begin in the gut or nose. It may spread via those migratory misfolded proteins into the brain — for example, in the brain’s sleep centers. Then, after several years, it may move into the parts of the brain where it causes problems with movement.
“Many Parkinson’s disease patients have experienced constipation or loss of the sense of smell, or experience violent dreams during which they move around or shout out,” said Brundin.
“Only a few who experience these symptoms will get Parkinson’s, but it’s giving us a clue that the disease may start outside the brain.”
Every protein, he said, is made up of a series of building blocks. In some rare forms of inherited Parkinson’s disease, one or two of those building blocks mutate in a protein that is prone to misfold.
“We’ve been able to see a protein move from one cell to another in the brains of mice, and through this move, they actually transmit the disease and make the recipient cell sick,” said Brundin, who is among other experts studying this phenomenon. “We didn’t think this moving around in the brain was a virus, which is how some diseases are transmitted, but we didn’t think it was a protein either.”
This knowledge could mean big strides in treating Parkinson’s disease.
“There are several highly effective treatments for Parkinson’s now, but they only treat the symptoms, and the patients always get worse over the years,” Brundin said.
“Perhaps in the future when a patient presents with a stiff arm or a tremor, we’ll be able to slow down or stop the disease so they’ll remain with only the slight symptom.”
The experts still don’t know what initially triggers Parkinson’s disease in the vast majority of cases. “During normal life, every cell probably creates several misfolded proteins, but most of the time they move them rapidly into the garbage disposal system inside the cell,” said Brundin.
“The single greatest risk for Parkinson’s disease is age. Younger people seem to hold off the bad cells. So possibly, the gradual failure of the garbage disposal system, which might develop inside cells as we age, is an important contributor to Parkinson’s disease.” GR