Brainsway aims to change the human brain, and indeed a cursory study of its history challenges one’s perceptions. The invention underpinning the company was registered at the US National Institute of Health (NIH), while financing came from a group of Israeli businessmen. An American invention with Israeli money? It takes a moment to digest.
You can now relax. This is an invention by two Israeli researchers, Yiftach Roth and Dr. Abraham Zangen, working for the NIH. Because they registered their patents in the US, the intellectual property is American. “The two men received offers for investment from all over the world, including large investors,” says Brainsway CEO Uzi Sofer, “and they decided to go with us.” Sofer was one of the group of investors that bought the patent rights from the NIH.
Sofer and Brainsway president Avner Hagai are probably well-known to those knowledgeable about the Israeli business world. They previously invested in Polysiv Plastic Products Ltd., Hofit - Kibbutz Kinneret Ltd., and General Defense and Technologies, which did some large deals with Israel Military Industries Ltd.. Sofer and Hagai invested a few million shekels in Brainsway. The company’s technological side is handled by Roth, Zangen and Brainsway chairman David Zechut, a gynecologist at Hadassah Medical Organization, who owns a number of medical centers in Israel.
Brainsway’s treatment is basically a greatly upgraded version of electroshock therapy the terror of patients during the 1950s and ‘60s. This treatment has garnered an awful public image, but it has been vastly improved in subsequent decades, and is now used to treat people suffering from depression who do not respond to medication.
Why use electricity or magnetism on the brain? The reason is that the brain is electrical. Neurons transmit by electricity, while information is transmitted between neurons by chemical signals. Psychiatric drugs affectthe brain by intervening in the chemical signals between neurons, whereas electroshock therapy is designed to affect the electrical current of the neurons themselves, to create a reaction. A magnet functions in the same way, because a magnetic current alters the flow and strength of an electrical current.
Although both psychiatric drugs and electric therapies have existed for years, the use of magnets is fairly recent. “In the past decade, researchers have been trying to prove that magnetic therapies are similar to electric therapies, but less invasive and with fewer side effects,” says Sofer. “No company has obtained US Food and Drug Administration (FDA) certification for this invention, but procedures are continuing. The treatment is sporadically used at Tel Hashomer Medical Center in Israel, with some success.
“The difference between all these methods and Brainsway’s method lies in Brainsway’s specificity. This is a well-knonw problem of drug therapies for depression, and electric therapies don’t solve it either. Both electroshock and drug therapies affect the entire brain and body, even though the intention is to only stimulate very specific locations deep within the brain, which are thought to be the active agents for depression and other psychiatric illnesses.”
The magnetic coil invented by Roth and Zangen at NIH sends a large number of magnetic fields through the brain. The coil is designed so that at the cortex, the electromagnetic fields cancel each other out, leaving no stimulation, while in the inner brain the electromagnetic fields strengthen one another, giving a stronger stimulation. The researchers say this stimulation treats depression without touching the whole body.
The part of the brain that Brainsway wants to stimulate is called the Nucleus Accumbens and the neurons that are in contact with it. “Very simplistically, you could say that this is the area of the brain that is responsible for positive stimuli,” says Zangen. “Whenever we do something that the body, or more accurately, the brain, identifies as positive, the Nucleus Accumbens environment records it as something ‘that feels nice, and I’ll do it again’. This area generates components of important feelings, such as motivation and pleasure, precisely the feelings that are missing in depression.
“We want to make a permanent change in the circuitry in these areas. A certain degree of artificial stimulation of electrical activity, created by the magnetic coil, will boost the sensitivity of these circuits. The next time a natural stimulation occurs in other words, something pleasant the brain will respond more strongly, enjoy it more, and motivate the body to repeat it. If the patient was depressed, intensifying sensitivity will cause him or her to respond normally to the environment.”
“Globes”: From what we’ve learned from the world of drugs, it seems that repeated artificial stimulation of the same areas of the brain causes habituation, not higher sensitivity. Why is the reverse true in this case?
Zangen: “It all depends on the strength of the stimulus. Drug addicts take very large drug doses from the start, which creates a very strong positive stimulus of the area, but apparently also causes the reverse effect a drop in sensitivity, due to the high dosages. On the other hand, an increased, but still low, dosage does increase sensitivity. We’ve seen that that’s how these circuits work.”
Good time for mice
Brainsway has been conducting clinical trials on humans since 2003, after animal tests proved successful. A preliminary small test was first conducted in the US, which showed the Transcanial Magnetic Stimulation (TMS) device was able to penetrate deep into the brain. Brainsway has now begun TMS safety tests at Shalvata Mental Health Center. The company will then have to show that TMS creates the promised effect on people.
Did have any problems finding test cases?
Zechut: “Not at all. People were very happy to participate in the trial when they understood its significance. Yes, even healthy people with no depression. They left the trial happier. Tests we conducted even showed improved cognitive abilities among these people.”
Brainsway even claims that lab rats enjoyed every moment of the animal trials. “We attached electrodes to the area in the rat’s brain that interested us, in order to see how an electric flow affected this area,” said Hagai. “We taught the rat that when there was a red light in its cage, the device was working, and it could get an electrical stimulation when it pressed the lever. The rats enthusiastically jumped on the lever, and wouldn’t let go, even to eat and drink, until the light was turned off.”
Isn’t there a risk of addiction to this sensation?
Zechut: “What’s addiction? We’re all addicted to things that feel good on which we depend. But none of the main signs of addition negative symptoms during rehabilitation, foregoing all other activities in favor of the drug, and the need for higher and higher doses have shown up in this electrotherapy. The test subjects claim that their depression has not returned, and that they don’t seek other therapies.”
Zangen: “After extensive research on the subject, I now believe that drug addiction is not caused by the drug’s effect on the inner brain. The problem with drugs is primarily their effect on the body as a whole, causing physical symptoms during rehabilitation. Another problem is the use of imprecise dosages, which causes tolerance to the drug, and the need for more and more drugs, which leads to theft and murder to get a fix. We’ve essentially created a kind of drug that is so precise that there are none of the risks we’ve found in drugs.”
Will you later offer TMS to everyone as a leisure device?
Sofer: “The Ministry of Health would never permit it.”
Zangen: “Why not? Maybe we will. This is a device that boosts motivation, so it can only benefit the economy.”
Hagai: “That’s not our intention at any rate.”
Cigarette? No thanks.
Brainsway has a lot of big plans for TMS. Depression is only the beginning. The company says TMS can change the way the brain works. The next step is treating addiction. Zangen says, “TMS apparently stimulates neural circuits linked with addiction. For example, we could wean a person off an addiction to cigarettes by using a strong magnetic field that reduces the neural circuits’ sensitivity. The next time the person smokes, he’ll feel nothing. Later, we’ll study treatments for Parkinson’s disease, schizophrenia, and maybe even autism.”
How will you market TMS?
Zechut: “We’ve designed a device very similar to an ultrasound device. The device, which costs $9,000 to $12,000, will initially be installed only at hospitals. It will later be installed at private clinics. It has been customized in advance to suit psychiatric clinics. We’ll market it through medical equipment distributors.”
Hagai: “We intend to remain an R&D company. Marketing won’t be part of the company’s structure. However, we don’t expect to be bought by a large medical devices company. We intend to finance our activities from equity until Phase I clinical trials are completed, in order to hold a financing round at a high company value.”
Published by Globes [online], Israel business news - www.globes.co.il - on August 18, 2005