Three years after the accident, Reynolds could walk no more than 25 meters, and then almost died of pain. But he had a passion and a dream.
Frank Reynolds has almost given up hope. The pain was constant. Clad in plaster cast from knees to neck, he lay on his back in his small Philadelphia apartment.
But before the car accident, everything seemed possible. Reynolds made final arrangements for the wedding, planned to pursue further education in addition to a psychotherapist's diploma and an administrative career in the hospital. But on the morning of December 14, 1992, as he was driving to work at the Philadelphia Psychiatric Center, another driver crashed into the back of his Oldsmobile Cutlass. When Frank was transported to the University of Pennsylvania clinic at night, he could not move. Then he found out that he had undergone surgery and replaced the displaced vertebrae of the middle spine, but one of them transmitted the spinal cord. It was an inoperable injury that prevented Frank from walking.
Life was fading away. He gazed at the ceiling for long hours, interrupting only for excruciating physical therapy sessions. Three years after the accident, Reynolds could walk no more than 25 meters, and then almost died of pain. He was only 30 years old, and the best spine injury specialists in the United States warned him that further improvement was unlikely, if not impossible.
But one day, in 1995, Reynolds' wife brought home a videotape of Lorenzo's Oil. It was the story of a couple who challenged the medical establishment to find a cure for a rare disease their son was suffering from. For Reynolds, this film was a revelation. “I thought, 'Lord, and I can do this,'” he says. Thus began his "crusade" to gain the ability to walk again.
He began to read everything he could find about spinal cord injury, or SCI. The Internet allowed him, lying in bed, to study the databases of university libraries, and thanks to acquaintances at St. Joseph's University of Philadelphia, where he studied before the car accident, he gained access to interlibrary exchange of hard-to-find medical publications. It was there that Reynolds came across the theory (which is supported by more and more specialists) that, by intensifying the usual rehabilitation regimen, it is possible to reactivate the faded nerve connections and revive the injured spine. Now, instead of the usual 45-minute therapy sessions three times a week, he did aqua therapy in the pool every day and did not leave the treadmill for hours - as long as he could bear. Grabbing the handrails of the simulator, wincing in pain, he forced his legs to step. Three months later, he walked 400 meters a day, a year later - already 8 km. Now he could move, both legs worked. He took off his plaster corset and prepared to return to work.
“Until now, it seems to me something unreal. I spent years lying in bed, dreaming about walks in the woods and along the seashore, about playing golf and not believing that this could happen, says Reynolds, who is now 45 years old. - For five years, looking at the ceiling, I repeated: "God, give me another chance."
One way or another, he received and realized this opportunity. But when this happened, he realized that a second chance just for himself was not enough for him. Then the second "crusade" of Frank Reynolds began.
Around 12,000 Americans suffer spinal cord injuries each year. Two thirds of them then experience chronic, often severe pain, and only one third of those affected return to work. Reynolds wants to give them a second chance too. And as co-founder and director of the Massachusetts-based new biomedical company InVivo Therapeutics, he won't stop until he gets there.
The 35-centimeter scar runs from the buttocks to the middle of his back. It is a constant reminder of what he is trying to accomplish. The stainless steel screws that hold his spine together are located just under the skin. When they get cold, he says, "It's like a little bomb." About the place where the surgeons removed the vertebra that transmitted his spinal cord, he says: “The only thing that protects my spinal cord is muscles, a layer of fat and skin. A blow with a twig could paralyze me. " These thoughts can drive you to despair - a hole in your back, pain, the knowledge that the nerve tissue of the damaged spinal cord is gradually dying off. But this forces Reynolds to always be collected.
Its goal is ambitious, in no small part because in fact we know little about the central nervous system, which consists of the brain and spinal cord, and the mechanisms for their recovery. “Figuratively speaking, we don't go deep into the phenomena, we just scratch the surface,” says Steve Williams, a spinal cord injury and rehabilitation specialist at Boston Medical Center. “It's like studying deep space, like a giant black hole. What's really going on there?"
The spinal cord can be thought of as a thick cable that carries information - a stream of electrical impulses. They continuously flow between the brain and the rest of the body, making movement and sensation possible. Motor signals flow downward from the brain; sensory signals from receptors travel upward to the brain. The core of the spinal cord - a gray matter, which is essentially a "tail", an extension of the brain - is enclosed in a sheath of fibrous white matter with long thin nerve filaments-axons that penetrate all parts of our body.
Normally, the delicate tissue of the spinal cord is protected by a flexible tube of 33 vertebral bones that make up the spinal column. But when these bones are knocked out of their usual place - most often caused by car accidents - the contents of the spinal column can be bruised, stretched, cut, or even torn. As a result, the passage of nerve signals is difficult or completely blocked at the site of injury, which condemns most SCI victims to paralysis of varying severity. According to medical statistics, more than 25% of patients with SCI suffer from complete paraplegia - they cannot feel their legs and cannot make them move; More than 20% of patients with SCI suffer from tetraplegia - paralysis of all four limbs and torso.
Physiotherapy aimed at restoring neural pathways is often able to improve a patient's vital functions months and years after a spinal cord injury. But Reynolds believes his technology can increase the chances of recovery thanks to the opportunities that open up in the immediate aftermath of injury. Often, the remaining intact spinal tissue is sufficient for neural bypass pathways to emerge, when signals are redirected, the flow of sensory and motor impulses is maintained. But hours and days go by, and the body's self-defense mechanisms are fading away. White blood cells come in to eliminate dead tissue, which causes severe inflammation. This, in turn, causes healthy cells in the surrounding tissue to destroy itself in a process called apoptosis. This secondary injury exacerbates the primary trauma and corresponding loss of function, creating a truly dead zone in the spinal cord that impedes recovery.
Reynolds and his team have developed a fingertip-sized implant device that is inserted into a wound to help the body deal with secondary damage. The implant is made from a polymer that has been approved by the FDA for use in biodegradable sutures. Apparently, the InVivo implant prevents apoptosis from developing, mainly due to the fact that it makes the body believe that the damage is not so great. This softens the immune response and helps healthy nerve tissue survive and heal.
Few companies specialize in the treatment of acute SCI. For the most part, emergency treatment remains at the same level today as it was during the car accident with Reynolds. Surgeons clean and stabilize the spinal column with screws and bone nails, and then suture the patient, leaving the spinal cord virtually unaffected. To reduce spinal cord inflammation, they may use a powerful steroid called methylprednisolone - also used to treat arthritis pain - although the side effects make it unsuitable for many SCI patients.
Recently, the US Food and Drug Administration (FDA) authorized the California company Geron to begin clinical trials of a method based on the use of human embryo stem cells for the treatment of SCI. Scientists believe that stem cells transplanted into the spine can develop into new nerve cells in the spinal cord. “Stem cells have great potential,” says Steve Williams at Boston Medical Center. “But other innovative technologies are also needed.” The device, developed by InVivo, Williams believes will be combined with, rather than compete with, stem cell therapies.
For Reynolds, who has spent five years in his quest to save lives and about $ 4.5 million, including most of his own savings, the moment has come. The first studies of InVivo's technology began in 2008. Since the final results of these studies were analyzed this spring - and the initial data were encouraging, it is now time to get FDA approval for human clinical trials and then bring this treatment to the market. This will require, according to Reynolds, another $ 15 million. But despite the fact that InVivo has a whole team of scientific advisers, including MIT professor and famous investor Robert Langer, no major investor has yet supported the project. But even if Reynolds is disappointed, he's not going to show it. For a CEO of a company with a dozen full-time employees and a research team made up primarily of graduate students and consultants, whose work is paid for by shares of the company, Reynolds exudes an amazing boost of self-confidence. “Reynolds is totally dedicated to his work,” says Professor Langer. - If it is necessary to go through the wall, he will do it. He gathered a very good team around him. But anyone can put together a strong team. Frank's strength lies in his unyielding determination to get the job done.”
Reynolds' day starts around 6 a.m. when he checks his email and usually ends after midnight - although the predawn emails to colleagues suggest that Reynolds rarely really rests. He drives his white Lincoln Navigator SUV with InVivo on board from the Boston suburbs to the InVivo headquarters. She occupies a small 14-seat office at the Cambridge Innovation Center, a business incubator a block away from the MIT campus. On the morning of November 9, other building tenants take turns entering the building while Reynolds begins the meeting in a small conference room overlooking the Charles River. Together with his executive assistant, 24-year-old Lauren Mitarondolo and (also 24-year-old) IT manager George Kalapai, he reviews data from research the company conducted at a research facility on St. Kitts in the Caribbean.
Regardless of your doubts about animal research, it’s hard not to share Reynolds’s sacred awe and excitement when watching videos of the trials organized by InVivo. The main point of Reynolds' presentation was carefully crafted for meetings with potential investors. The video shows two African green monkeys whose spinal cord has been partially damaged in order to paralyze one of the hind legs. Two days after the injury, both monkeys in the video are barely dragging their feet with them. But after two weeks, one of the monkeys - the same one with the implant from InVivo - not only walks, but also runs, bending its tail and easily leaning on its previously paralyzed leg. Reynolds believes that his device will bring about the same amazing results in the treatment of people.
In 2008, the company conducted the first clinical trials on four animals, all of which yielded similar results. The second trials on more monkeys started unsuccessfully and were soon discontinued. Exactly what went wrong has yet to be figured out, but Reynolds believes the hardware was the reason. He held talks on this issue, in connection with which he says that he is "very happy." However, a bad start knocked InVivo out of schedule. The company expected to begin human clinical trials in early 2010 - from now on, they will be pushed back to the earliest in the third quarter of the year.
So the InVivo team went back to St. Kitts to conduct a trial involving 16 animals. This is enough to produce results that can be reported to the FDA as definitive. In addition to the video, an analysis of the motor activity of animals was carried out using electromyography data. Extensive data has been collected, and Reynolds sternly asks Kalapai if he is confident that all the data is carefully documented and preserved. When Frank applies for approval for clinical trials in humans, he wants to make sure that all the data is absolutely reliable. And he thinks that they will be. “It will blow them away,” he says. - Nobody has come and said: 'Look at this running animal and at the data of bioelectric activity.' They've never seen anything like this. It really worries."
Reynolds has always been more of an optimist. The son of Irish immigrants, he grew up in the Bronx. He worked as a shoe shiner on weekends to earn money for his personal needs. When the family moved to New Jersey, Reynolds delivered newspapers, brought golf clubs and balls at a local golf club, and worked in restaurants. He attended Catholic schools and played football, basketball and golf in college. When he was 17 years old, his father contracted Parkinson's disease. At the age of 18, Reynolds, without leaving college, was already running the family business, which included restaurants, bars and real estate. “My father seemed to have left the stage and did not even always recognize me,” he says. "It was 25 years of agony and pain for our family."
A car accident canceled out Reynolds' plans for a new career, and years of treatment took a heavy toll on his financial situation. When his strength returned, he had already abandoned plans to run the hospital and began to look for a higher-paying job. Frank was confident that he would easily find her. Employers, he thought, would be impressed by his amazing healing. But they turned out to be paying attention to the long hiatus on his resume. “It was a shock when they told me that I had not worked for six years,” says Reynolds."But I worked."
And Reynolds, who became familiar with the power of the Internet while looking for a miracle cure, started his own business, Expand the Knowledge, an IT consulting firm that would help medical researchers coordinate online work. “I worked 100 hours a week and slept 3-4 hours a day. I wanted to make the most of my second chance.” Then, having sold his business and received additional education in technology and engineering management, Reynolds went to work in the American division of Siemens USA. In the American division of the German electronics giant, he was spotted as an aspiring leader and sent to undergo a special mentoring program. He soon worked as Director of International Business Development. In 2005, Siemens USA invited him to become a Sloan Fellows student at the Massachusetts Institute of Technology (MIT). Alumni of this prestigious one-year MBA program for career advancement executives included Kofi Annan and Karli Fiorina.
At MIT, Reynolds listened to Langer's talk about a new treatment for SCI. Professor Langer, with his 750 patents issued or pending worldwide, was one of the first to apply chemical engineering methods to medical development. In particular, he pioneered the use of specially designed polymers for targeted drug delivery and tissue repair. About 100 researchers in his laboratory are developing these directions. Licenses for the technologies they developed were bought by 220 pharmaceutical, chemical, biotechnical companies, as well as medical equipment developers.
In the mid-1990s, Langer and colleagues at Harvard Medical School explored the idea of using biomaterials in combination with cells or drugs to improve performance after SCI. In 2002, he published the results of experiments on rodents. After Reynolds met him and told him the story of his recovery, Langer asked him to be the unofficial "business manager" on his SCI team. Reynolds helped with grant applications, researched the market prospects for SCI treatments, analyzed research data, and thought about product development strategies. All of this culminated in his MBA thesis titled InVivo Therapeutics - and a business plan for a company of the same name that could take Langer's developments outside the laboratory and elevate testing to primates and finally humans. In November 2005, Reynolds registered the company, signed a contract with the research laboratories of MIT, and informed the management of Siemens, the company he loved.
“It was a great prospect for Frank to come back to us,” says former Siemens USA CEO George Nolen. - But he had a passion, he had a dream. It's hard to lose talented people, but I told him: “Only once in your life can you realize your main dream. God bless you and those who want to help you."
Reynolds crosses the parking lot on a trajectory that takes him three minutes from his office to Langer's lab at MIT. He looks like a doll-faced Irish gangster. He wears a pinstriped English suit, metallic tie, designer glasses and an MIT signet ring, denoting what he jokingly calls the "secret society." As always, he is accompanied by Mitarotondo. They go to meet with Chris Pritchard, a 24-year-old Langer protégé, an Oxford and MIT graduate who heads InVivo's research and development activities.
Reynolds is not embarrassed by the fact that he prefers to hire young people. “As the company grows, we will need people with authority and experience,” he says. “And at this early stage of innovation, you need fast, smart employees who don’t have preconceived opinions and prejudices.” Moreover, he adds, no one knows as much about science as Pritchard. When launching biotechnological business projects based on the use of the most modern technologies, it is often the graduate students who turn out to be the most competent and accessible specialists for the company. At the same time, the price of cooperation suits both parties. InVivo paid for Pritchard's year of graduate school and funded his research at Langer's lab. In return, Pritchard brings to InVivo his uncommon ability, refined in some of the most intelligently sophisticated research ever done in biomaterials.
In addition to Pritchard and InVivo's medical director, distinguished Boston neurosurgeon Eric Woodard, the company's current R&D team consists of consultants and a small group of renowned advisors, including 1993 Nobel Prize winner in medicine Richard Roberts, who works for InVivo for stock options. (Langer and Woodard receive consulting fees in addition to options.) Roberts, who works in a biolaboratory in New England, has personal reasons for wanting InVivo success: his eldest son is paralyzed after a car accident.
In a cramped, cluttered conference room outside Langer's office, Reynolds and Pritchard begin their meeting by discussing a schedule for publishing InVivo's primate research. The goal, Reynolds says, is to create a coherent series of trials that should lead to clinical trials in humans this year. They are now, however, discussing a blueprint for a future science journal article in which they will describe In Vivo technologies to compare the severity of SCI and the chances of recovery in primates. The longer article, which Pritchard and Langer are going to submit to the influential journal Nature, will describe all of the findings, including the latest analyzed primate trials - provided, of course, that the results are good.
While they await these results, Reynolds and his team are laying the groundwork for the next generation of In Vivo products. One of them is imagined by Reynolds as a specialized medical complex, where spinal injuries are treated. His biggest dream is for InVivo to be as big and influential as the other biotech firms in the neighborhood. “I expect we will be the second Biogen in the future,” says Reynolds. Given that Biogen is a $ 64 billion phramacology giant specializing in cutting-edge therapies for cancer and autoimmune diseases, Reynolds' hopes seem odd, if not slightly delusional. On the other hand, Biogen also started out as a small firm founded in 1978 by scientists at MIT and Harvard. Sitting in small, scattered laboratories, they drew on theories that were then perceived as radical, constantly fell into research dead ends, and more and more got into debt, until the overly successful drugs for leukemia, multiple sclerosis and non-Hodgkin's lymphoma brought them huge commercial success.
Of course, the market for SCI drugs is smaller than the market for cancer drugs. But if doctors, patients and - perhaps most importantly, insurers - decide that the implant invented by InVivo is worth the $ 100,000 it is asking for, then annual sales could surpass the billion dollar mark. And drugs for chronic diseases can bring even more income. One day, Reynolds says, InVivo's version of the implant, combined with stem cell or hormone therapy, will take the lives of 6 million Americans paralyzed by SCI or other diseases of the central nervous system to a new level. And IVivo injectable biomaterials can prove to be a valuable treatment for spinal cord injuries due to spinal compression and other diseases.
With visible enthusiasm, Pritchard shows Reynolds the slides of rodent tissue that he just received from W. Reggie Egerton, an SCM expert at the University of California and a member of the InVivo research team. The slides show a detailed picture of what happens in the spinal cord as a result of its injury. Do the images show a dramatic picture of the progression of the secondary lesion? and a chaotic molecular environment in which routine drug delivery to diseased tissue sites becomes dangerous. This is why Reynolds and others are counting so much on the potential of their biomaterials.
Towards the end of the meeting, Reynolds sits in a small, uncomfortable chair. His face turns red and he grimaces. Pain is a constant part of his life. “I was well in my thirties when the doctor said I had the spine of a 70-year-old man,” he says. And now and then his legs go numb, and he gets up to walk a little, to make sure that everything is all right with him. More recently, injections into the spine have helped him keep pain under control. “To keep my spine in order, I need to bring my design to market,” he says. "Then I can work until 11 pm."
There are complex scientific matters behind InVivo technologies, but the question of how to finance them is perhaps even more complex. If you just want to get rich, you better do something else. The US federal budget is the main source of funding, but it doesn't help much either. In 2008, the National Institutes of Health spent $ 80 million on TCM research - about the same as on inflammatory bowel disease. Compare this with $ 5.6 billion for cancer research, and $ 3.6 billion for infectious disease research.
This year, InVivo received additional funding from the Massachusetts Center for Life Sciences, a science-based business support agency that provided the company with a $ 500,000 unsecured research loan. “Our experts considered this technology to be unique and innovative,” says Center Director Susan Windham-Bannister.
Still, Reynolds has not yet managed to sufficiently interest the venture capitalists, who sometimes seem to hide behind every tube in Cambridge. This comes as no surprise to Pitrick Fortune, co-owner of the life sciences and health care venture capital firm Boston Millennia Partners. Due to the relatively small market and unpredictably long tests, TCM is not an area where investments would be massively flocked. “This is a tricky area,” says Fortune. - In it, science still misunderstands a lot or does not understand at all. Without enough evidence from clinical studies in animals or humans, it is difficult to raise funds here.”
In addition to a grant from the Massachusetts Center, a dozen of Reynolds' friends and family and himself invested in InVivo (during these years he had successful business at Siemens). The constant lack of funds held back the work, but it also helped to rationally organize the activities of InVivo. The path to human clinical trials was completed in less than five years and at less than $ 5 million. It usually takes twice as long and costs much more. But even if the investment issue succeeds - and Reynolds is confident that it will - there are still many different pitfalls ahead. “We faced obstacles at almost every stage,” says Langer. - Anything happens. You have to be ready for this."
By the evening, in negotiations with an analyst at a large investment firm, Reynolds is balancing on a fine line: he is overwhelmed with confidence in his abilities, but he tries to be restrained. "Our muscles are pumped up!" he says.
He's eager to lay out the details of clinical studies in animals: the fact that all treated monkeys are now walking. But until complete data is available, Reynolds is trying to contain his enthusiasm and carefully release the information. The analyst ends the conversation with a vague promise to continue the conversation.
Reynolds has been working nonstop for 12 hours. For a moment, his energy seems to have run dry. But then an email comes to his iPhone. This is the analyst he just met. He already has some news: his firm confirms a meeting with Reynolds. Will this be of any use? Maybe not. But Reynolds believes that a constant stream of meetings and presentations is the basis for fundraising and partnerships. “I have to create chances,” he says. "If they are not there, I have lost."
The sun is already setting across the Charles River when we enter Reynolds' office. It is cramped, windowless, and one of the most modest in the building. Younger employees take up much more street-facing space along the entire lobby. Reynolds doesn't care about these things. On the wall of the cabnet hangs a photograph of his character, Hollywood actor Christopher Reeve, who did not fold his arms after a spinal fracture, and also a color print similar to a photo taken by an accidentally triggered camera - it shows a half-darkened ceiling.
“I saw this when I was paralyzed,” says Reynolds. - I imagined that from the darkness I was moving towards the light. This photo hung in all the offices in which I have worked since then. It also hangs in the offices of its employees, and each of them, joining the company, receives a copy of the film "Lorenzo's Oil".
10 questions for Frank Reynolds:
1. What is your favorite time of day?
The first hour after waking up, when I am alone with my thoughts.
2. What part of your job would you like to give up?
From collecting and attracting finance.
3. Who gives you the best advice?
My scientific advisory board, my board of directors, and my high school friends.
4. What prevents you from sleeping at night?
Search for money.
5. If you were starting a business in another area, which one would you choose?
A healthcare venture capital firm.
6. What are you most afraid of?
Lose my faith and spiritual strength.
7. What's your main quirk?
Subscription to the games of the New York Jets.
8. What talent would you like to have?
Be able to read other people's minds.
9. What is your most precious thing?
Photo of my daughter, taken at Christmas 2002, the day we adopted her in Russia.
10. What skill would you like to improve?
I would like to learn how to achieve any degree of patience.