Approximately 18.8 million American adults suffer from depression, the leading cause of disability in the United States. Yet only about half the patients who take common medical treatments like antidepressant drugs actually see a therapeutic effect. Moreover, they suffer a broad range of undesirable side effects including weight gain, sexual dysfunction and even suicidal behavior.
Electroconvulsive therapy (ECT) has a far higher success rate, with some 80% of patients responding positively. ECT, however, is a highly invasive treatment involving general anesthesia, with many serious side effects ranging from dizziness and headaches to temporary or even permanent memory impairment.
Now an Israeli company, Brainsway, has developed a new non-invasive deep Transcranial Magnetic Stimulation (TMS) treatment that it claims can effectively treat depression without any of the negative side effects of drugs or ECT. The treatment, which Brainsway's founders believe could revolutionize the whole psychiatric care market, does not require anesthetic. Instead, users describe the experience as a gentle shaking or tickling of the scalp. "A bit like a massage," Dr. Abraham Zangen, one of the inventors of the device, told ISRAEL21c.
TMS is still a relatively experimental area of medicine that is primarily being used for research purposes and clinical trials only. Though widely recognized as a potential treatment for a number of mental disorders including depression, the problem until now has been that existing TMS devices can only penetrate about half an inch beneath the surface of the cortex. This is deep enough to treat some disorders like migraine (a new TMS device to treat migraines is now being tested in the US,) but not deep enough to treat more difficult mental health conditions.
Brainsway's founders, however, have invented a new TMS coil configuration that has been designed to generate sufficient magnetic field strength to stimulate neurons which are located 5 to 6 cm. inside the brain mass without posing a hazard. This, according to Zangen, means the device can potentially be used to treat a wide range of mental illnesses including depression, Alzheimer's, Parkinson's disease, addiction, stroke, drug abuse, Post Traumatic Stress Disorder (PTSD), and schizophrenia.
The magnetic coil, which is placed on specific areas of the patient's scalp, sends strong directed magnetic pulses through the brain to stimulate the Nucleus Accumbens (the part of the brain responsible for positive stimuli) and the neurons connected to it. "By repeated artificial stimulation of electrical activity created by the coil, we boost the sensitivity of these circuits so they will work more efficiently," says Dr. Hilik Lewkovitch, at Brainsway.
The result is that the next time natural stimulation occurs, such as something pleasant that the brain responds to, the patient will respond more strongly, enjoy it more, and seek to repeat the experience. By intensifying sensitivity this causes the patient to respond normally to the environment.
What makes the device so unique in terms of treatment is that unlike ECT or drugs, it stimulates a specific area within the brain, rather than the whole brain or body. This is a well-known problem for drug therapies used to treat depression. Both ECT and drug treatments affect the entire body, even though the intention is to only stimulate certain locations deep within the brain which are thought to be the active agents for depression and other psychiatric illnesses.
Uzi Sofer, Brainsway's CEO, believes the company's device could become the first line of treatment for depression, a replacement not only for ECT, but also for anti-depressants themselves. "It may become the safe and effective treatment for a person's first depressive episode," he predicts.
Brainsway has undertaken successful animal trials at the Weizmann Institute of Science, where the device was tested as a treatment for depression, addiction, and PTSD. "These were a great success," says Lewkovitch. From June to November last year, the company held its first clinical trials to test the safety of the treatment. Thirty-five people took part in the study that was held at the School of Medicine at Tel Aviv University. "We found that not only was the device safe with no obvious side effects, but that even healthy patients who did not suffer from depression reported an improvement in positive feeling and some cognitive improvement," says Lewkovitch. "This was very good and encouraging news."
The company is now preparing to begin a multi-center clinical trial this month in three or four locations around the world. This will test the efficacy of the treatment, specifically related to emotional and cognitive improvements. The trial, which should take between seven to eight months, is for moderate to severely depressed patients who have not responded to medication.
Brainsway is now meeting with the FDA to approve its clinical strategy. The company hopes to receive FDA approval and CE approval at the same time, enabling the company to begin sales in both Europe and the United States in 2008 or 2009. The company's goal is to start by targeting depression, and then move to other areas of mental health.
In 2005, Brainsway carried out a study on a single Alzheimer's patient. The patient, who is the wife of a well-known physician in Israel, had been treated with every new cutting edge drug and cognitive treatment available, but her situation was getting worse. The family won approval for an emergency treatment with the Brainsway device. Brainsway carried out two weeks of treatment, directing the magnetic pulses at brain regions related to Alzheimer's. The patient was given 60 pulses of TMS a day in half-hour treatments.
"The case study was very promising," says Zangen. "The patient showed cognitive improvement in remembering names and in motoric exercises. When we tested her after treatment she was able to remember more family names and her score was in the normal range of memory for her age." The patient did not, however, show total improvement in other aspects of memory and cognition. The company plans to carry out another longer-term study with the same patient. The family of the patient has now applied for permission to continue the trial with the Israeli Health Ministry.
Brainsway is also now about to sign an agreement with a well-known US laboratory that plans to carry out a study of the company's device on patients suffering from Alzheimer's and autism.
The market for treatment of mental and brain diseases is enormous. Today the annual global market for Central Nervous System therapies is in the region of $65 million. Of this, every year, worldwide, some $15.9 billion is spent on depression therapies. Brainsway estimates that the worldwide deep TMS market for depression treatment alone could reach $20 billion over the next 10 years.
The technology behind Brainsway was invented by Israeli researchers, Zangen, and Yiftach Roth while they were working at the US National Institute of Health (NIH) in the late 1990s. It took four years to invent the new deep TMS coil, and their work was patented by the NIH in 2001. Soon after, articles began to appear in the science press about the new device.
The device attracted the attention of a well-known Israeli high-tech entrepreneur who was interested in creating a company to develop the patent. He set up Brainsway with a number of other investors, including Sofer, and incorporated it in Delaware in 2003. A short time later, he opened a subsidiary in Jerusalem.
The company now employs eight full-time workers and numerous sub-contractors from the Weizmann Institute amongst other places. So far the company has raised several million dollars in investment from three internal investors, Dr. David Zechut, a gynecologist at Hadassah Medical Organization; Avner Hagai, Brainsway's president; and Sofer.
Sofer admits that the company has started looking for large multinational partners such as medical device companies that can help the company take the device to the market. Already Brainsway has been approached by a number of companies who are interested in the device.
"My goal is that Brainsway will become a multi-centre of development, creating a number of different applications for this technology," says Sofer. "Depression is only the first step for Brainsway. We hope to develop many new applications for Alzheimer's, PTSD, and addiction. We want to specialize in R&D, and hope to find strategic partners that can do the other work of marketing and sales."
"Within a decade hopefully it will be clear that this is a revolution in psychiatry," says Zangen. "This will become the standard way of treating many diseases that today are treated poorly and with too many side effects."
