Can a Non-Invasive Magnetic Helmet Treat Brain Cancer?
Glioblastoma is an aggressive and deadly brain cancer, causing more than 10,000 deaths in the US per year. In the last 30 years there has only been limited improvement in the survival rate despite advances in radiation therapy and chemotherapy. Today the typical survival rate is just 14 months and that extra time is spent suffering from the adverse and often brutal effects of radiation and chemotherapy.
Scientists are trying to design more effective treatments for glioblastoma with fewer side effects, and a team at the Department of Neurosurgery at Houston Methodist Hospital has created a magnetic helmet-based treatment called oncomagnetic therapy: a promising non-invasive treatment for shrinking cancerous tumors. In the first patient tried, the device was able to reduce the tumor of a glioblastoma patient by 31%. The researchers caution, however, that much more research is needed to determine its safety and effectiveness.
How It Works
“The whole idea originally came from a conversation I had with General Norman Schwarzkopf, a supposedly brilliant military strategist,” says David Baskin, professor of neurosurgery and leader of the effort at Houston Methodist. “I asked him what is the secret to your success and he said, ‘Energy. Take out the power grid and the enemy can't communicate.’ So I thought about what supplies [energy to] cancer, especially brain cancer.”
Baskin came up with the idea of targeting the mitochondria, which process and produce energy for cancer cells.
"This is the most exciting thing in glioblastoma treatment I've seen since I've been a neurosurgeon, but it is very preliminary,” Baskin says.
The magnetic helmet creates a powerful oscillating magnetic field. At a set range of frequencies and timings, it disrupts the flow of electrons in the mitochondria of cancer cells. This leads to a release of certain chemicals called Reactive Oxygen Species, or ROS. In normal cells, this excess ROS is much lower, and it's neutralized by other chemicals called antioxidants.
However, cancer cells already have more ROS: they grow rapidly and uncontrollably, so their mitochondria need to produce more energy which in turn generates more ROS. By using the powerful magnetic field, levels of ROS get so high that the malignant cells are torn apart.
The biggest challenge was working out the specific range of frequencies and timing parameters they needed to use to kill cancer cells. It took skill, intuition, luck and lots of experiments. The helmet could theoretically be used to treat all types of glioblastoma.
Developing the magnetic helmet was a collaborative process. Santosh Helekar is a neuroscientist at Houston Methodist Research Institute and the director of oncomagnetics (magnetic cancer therapies) at the Peak Center in Houston Methodist Hospital. His previous invention with colleagues gave the team a starting point to build on. “About 7 years back I developed a portable brain magnetic stimulation device to conduct brain research,” Helekar says. “We [then] conducted a pilot clinical trial in stroke patients. The results were promising.”
Helekar presented his findings to neurosurgeons including Baskin. They decided to collaborate. With a team of scientists behind them, they modified the device to kill cancer cells.
The magnetic helmet studied for treatment of glioblastoma
Dr. David Baskin
Initial Results
After success in the lab, the team got FDA approval to conduct a compassionate trial in a 53-year-old man with end-stage glioblastoma. He had tried every other treatment available. But within 30 days of using the magnetic helmet his tumor shrank by 31%.
Sadly, 36 days into the treatment, the patient had an unrelated head injury due to a fall. The treatment was paused and he later died of the injury. Autopsy results of his brain highlighted the dramatic reduction in tumor cells.
Baskin says, “This is the most exciting thing in glioblastoma treatment I've seen since I've been a neurosurgeon, but it is very preliminary.”
The helmet is part of a growing number of non-invasive cancer treatments. One device that is currently being used by glioblastoma patients is Optune. It uses electric fields called tumor treating fields to slow down cell division and has been through a successful phase 3 clinical trial.
The magnetic helmet has the promise to be another useful non-invasive treatment according to Professor Gabriel Zada, a neurosurgeon and director of the USC Brain Tumor Center. “We're learning that various electromagnetic fields and tumor treating fields appear to play a role in glioblastoma. So there is some precedent for this though the tumor treating fields work a little differently. I think there is major potential for it to be effective but of course it will require some trials.”
Professor Jonathan Sherman, a neurosurgeon and director of neuro-oncology at West Virginia University, reiterates the need for further testing. “It sounds interesting but it’s too early to tell what kind of long-term efficacy you get. We do not have enough data. Also if you’re disrupting [the magnetic field] you could negatively impact a patient. You could be affecting the normal conduction of electromagnetic activity in the brain.”
The team is currently extending their research. They are now testing the treatment in two other patients with end-stage glioblastoma. The immediate challenge is getting FDA approval for those at an earlier stage of the disease who are more likely to benefit.
The Future
Baskin and the team are designing a clinical trial in the U.S., .U.K. and Germany. After positive results in cell cultures, they’re in negotiations to collaborate with other researchers in using the technology for lung and breast cancer. With breast cancer, the soft tissue is easier to access so a magnetic device could be worn over the breast.
“My hope is to develop a treatment to treat and hopefully cure glioblastoma without radiation or chemotherapy,” Baskin says. “We're onto a strategy that could make a huge difference for patients with this disease and probably for patients with many other forms of cancer.”
Gene Transfer Leads to Longer Life and Healthspan
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman