InVivo Therapeutics, based in Cambridge, Mass., was founded to focus on research and development of treatment for patients with spinal cord injuries (SCI). Currently, there are no effective treatments for these patients, and much of the research focuses on treating the symptoms of SCI instead of the underlying pathology.
However, InVivo has focused its efforts on both regenerative medicine and neuroprotection. Its scaffolds are designed to mitigate inflammation and prevent further cell death after SCI as well as support the repair and neuroplasticity recovery process. Co-founded by CEO and CFO Frank Reynolds and Robert Langer, ScD in 2005, InVivo Therapeutics and its scientific team have made incredible progress over the past few years and are now poised to bring the technology to human patients, which has created a stir in the global medical community.
Jonathan Slotkin, MD, a clinical neurosurgeon with an expertise in spinal cord injury and medical director of InVivo Therapeutics, discusses the company’s technology and the progress it expects to make in the near future.
InVivo Therapeutics’ implant technology is based on research done by Robert S. Langer, ScD, and Joseph P. Vacanti, MD, which they completed out of their labs at Massachusetts Institute of Technology and Massachusetts General Hospital in Boston. The first formulation was a PLGA PLL biodegradable polymer scaffold, a device that can also be seeded with autologous hNSCs, which was followed by an injectable self-assembling, drug-releasing form of the scaffold. The scaffolds are applied directly to the spinal cord and nervous stem to promote neuroplasticity and decreases in secondary injury.
“This is truly a disruptive technology in the sense that it represents the best of the movement to interact directly with the affected tissues instead of through indirect routes,” says Dr. Slotkin. “I think it represents an entire sea change in how we see treating nervous system injuries. We are finishing decades of indirect and intravenous treatment for spinal cord injury and are now spearheading the notion of treating SCI by directly interacting with the tissue for biomaterial and structural support.”
A few months ago, the company expanded technology indications to include peripheral nerve injuries (PNI), such as patients with chronic nerve compression symptoms and peripheral nerve injury. In the future, the company is hoping to partner with Geisinger Health System in Danville, Pa., to perform PNI studies.
The research and development team have tested the scaffolds on rodent and primate models of spinal cord injury and have published their results. The studies showed behavioral improvements as well as improvements at the cell and molecular level. “We see decreased cavitation and tissue loss at the cell and molecular level, as well as decreased glial and other scarring around the injury site,” says Dr. Slotkin. “It has been extremely exciting — we are talking about trying to find an effective treatment for a currently devastating and untreatable condition affecting many people around the world.”
The American Spinal Injury Association has honored the company’s work with the primate model as the top research in the field of spinal cord injury for developing the first device that would allow monkeys with spinal cord injuries to regain locomotor function after injury. “We have seen significant improvement in our work in animals following spinal cord injury, some of which has been published, and the rest we look forward to having peer-reviewed,” says Dr. Slotkin. “Our research has shown signs of behavioral, cell and molecular improvement, demonstrating the benefit of our treatment after spinal cord injury.”
Currently, the formulation of the scaffold submitted for approval by the Food and Drug Administration is the biomaterial-only version of the scaffold, although the company has published studies on the form of the scaffold that contained stem cells. The company is in conversation with the FDA about using the biomaterial-only version for IDE trials, and has a positive feeling about pushing forward in the near future.
“We are excited with the FDA’s feedback and pleased with the constructive commentary they’ve given us,” says Dr. Slotkin. “In the near future, we also plan on submitting the injectable formulation of the scaffold for approval as well.”
With approval from the FDA, Dr. Slotkin says the company hopes to begin human trials in 2012. The company hopes to conduct human trials in the injectable formulation of the scaffold relatively soon as well. If they are granted open label trials, they’ll be able to keep the spinal cord injury community informed of the progress as they push forward. “Our first goal is to assess the safety of the devices, but we will also be looking for efficacy,” says Dr. Slotkin.
One of the big questions in the spinal cord injury research field right now is how fast surgeons should apply treatment after the injury occurs. “Our feeling as scientists and as a company is that the earlier you can intervene, the better. We believe this increases the chances of decreasing the risk of secondary injury after SCI,” says Dr. Slotkin. “In SCI there is the primary injurious mechanism followed by a cascade of injury that comes afterward over the next few weeks. The earlier you can intervene to stave off that injury, the better, in our opinion.”
Ideally, medical professionals will be able to intervene within 24-48 hours of the initial injury, says Dr. Slotkin. The trials for InVivo’s technology will take patients within a week or 10 days after injury, depending on FDA indications. There are some treatments proposed for human use that suggest treating up to three weeks after the initial injury, but InVivo believes that for optimal results, surgeons should treat patients as quickly as possible. Some treatments focus on using stem cell technology while others administer drugs to enhance healing.
InVivo’s scaffolds can be applied alone, with stem cells or with enhancing drugs to promote healing. “Other proposed solutions face the challenge of getting the drugs or cells to the nervous system, maintaining them there and releasing them,” says Dr. Slotkin. “Our scaffolds are a platform technology that can deliver drugs or cells to the nervous system in a controlled way.”
Collaborative treatment approach
There are some scientists and researchers that focus on the regenerative aspect of treating spinal cord injury using stem cells while others only pay attention to nerve damage. Several companies are pursuing a cellular approach to treating SCI, but haven’t identified the best cell line yet. As a company, InVivo Therapeutics has taken a multi-faceted approach examining all aspects of spinal cord injury treatment to pursue functional restoration.
“If you take a group that only looks at stem cells for spinal cord injury patients, the spinal cord is subject to significant tissue loss and physical cavitation,” says Dr. Slotkin. “Tissue engineering is one way to potentially overcome that cavitation and provide structural support for the spinal cord. It’s a leap to ask stem cells to overcome a hole in the spinal cord, and I think that’s where tissue engineering and scaffolds will have a seat at the table.”
InVivo has partnered with The Miami Project to Cure Paralysis, a group dedicated to finding effective treatment for patients with spinal cord injuries. The partnership is a mutual collaboration in technology and knowledge transfer between the two groups, combining InVivo’s experience in biomaterials with The Miami Project’s cellular expertise using Schwann cells.
“The Miami Project has spent three decades learning how to optimize the cellular treatment of SCI patients,” says Dr. Slotkin. “We thought it would benefit patients if we partnered with the Miami Project because they have extensive cellular experience and we have biomaterial expertise. Our collaborative relationship benefits both groups, and ultimately patients will have better treatment options.”
Written by Laura Miller