Author: invivotx

A Q&A with Nobel Prize Recipient Sir Richard Roberts, Ph.D., F.R.S.

Sir Richard Roberts won the Nobel Prize in Physiology or Medicine in 1993 for the discovery of the mechanism of gene splicing, which opened the door to new insights into therapeutics development.

He has a very personal connection to the mission of InVivo Therapeutics: His son Andrew was in a car accident at age 20 and suffered a severe spinal cord injury that left him unable to move his arms or legs. Hoping to make a difference for other families with spinal cord injury, Dr. Roberts later joined the scientific advisory board and the board of directors at InVivo, which is developing the Neuro-Spinal Scaffold^TM for the treatment of acute spinal cord injury.

Dr. Roberts is the chief scientific officer of New England BioLabs, which specializes in the discovery, development and commercialization of reagents for genomic research.

We talked with Dr. Roberts about his son’s spinal cord injury, the standard of care for treatment – and the potential for future improvements.

---

Could you please share a little bit about your family’s experience with spinal cord injury?

We got a call in the middle of the night, telling us our son had been in a car accident and was badly injured. They didn’t know how long he might have to live. I got down there as fast as I could.

Andrew was in Florida at the time of his accident. He was in the Navy and had been on leave for the day, and he was driving back to his base when a drunk driver plowed into him. He was 20 at the time.

It was a very difficult time.

What was it like as a family adjusting to your new reality?

It took a lot of time and attention to ensure Andrew was getting proper care. The emotional toll was the most difficult part. Every day when I was driving to the hospital, I’d be wondering, what am I going to find when I get there? On the way back, I’d be wondering: What more could I have done? What didn’t I do? It’s devastating from an emotional standpoint as a parent.

Andrew actually deals with it better than I do. He spent time at The Courage Center in Minneapolis, where he received a lot of psychological counseling that empowered him to take charge of his situation. The Courage Center was heavily focused on ensuring that Andrew was able to make the most of his ‘new normal’ and restore whatever independent function he could.

After rehabilitation, Andrew was able to live on his own, with the support of a caregiver. He attended University of California, Berkley and pursued a degree in computer science for a few years.

What has he done in the years since?

He finds it more difficult to move about in his wheelchair now and he has to spend a lot of time in bed, so he enjoys activities that stimulate his mind.

He and I used to play chess over email all the time. As a kid, he’d never beaten me. Then suddenly I noticed that he was getting progressively better. One day, he beat me. Eventually, he confessed that he had been taking lessons from a Russian grand master.

He communicates a lot with friends by email and Zoom. He loves movies and documentaries. Once a year, he goes into New York City to visit friends and go to the theater. He deals with it much better than I do.

As a scientist who has made groundbreaking discoveries, do you believe the field of spinal cord injury is ripe for innovation?

I have felt that way for a long time. The standard of care really has not changed in 30 years.

That is why I wanted to get involved with InVivo.

When I first heard about Bob Langer’s innovation and learned that spinal cord regeneration might be possible, I was really excited. Even though I knew it would not be possible to help my son, I thought it would be great if this technology could help others.

Those of us who live a “normal” life have a hard time imagining what it means to live with spinal cord injury.

The standard of care really has not changed in 30 years.

What can we do to encourage more scientific and clinical innovation?

I often say that anything worth doing is risky. If you’re not prepared to take a risk, you will not make a great advance.

You also have to know that it takes a long time to get from a basic scientific discovery to an approved drug. I made the discovery for which I won the Nobel Prize in 1977, and it was just three years ago that the first clinical application came to fruition. In my case, it took 40 years for my research to reach the clinic.

Bob Langer, InVivo’s co-founder and an inventor of the Neuro-Spinal Scaffold, is a great example of someone who has repeatedly translated basic research into medical innovation. He is a great model.

What do you hope the Neuro-Spinal Scaffold could accomplish?

The beauty of the of the Neuro-Spinal Scaffold approach is that, once it is shown to be safe, InVivo can evaluate other approaches used in combination with the scaffold. For instance, you could add neural stem cells or therapeutics that would encourage restoration of neuronal connections.

For me, the first goal is to get the scaffold approved and see that it is useful for patients. That would open the door for the next stage of innovations, which I think could make a real difference.

A Q&A with renowned inventor Robert S. Langer, Sc.D.

Robert S. Langer is one of the most prolific inventors and company founders in the biotech industry.

A chemical engineer by training, Dr. Langer has invented the technologies behind more than 1,360 issued and pending patents worldwide; those discoveries have been licensed or sub-licensed to more than 400 biopharma, chemical and medical device companies.

Dr. Langer is one of 12 Institute Professors at the Massachusetts Institute of Technology – the highest honor that can be awarded to a faculty member at MIT. He has received hundreds of major awards, including the National Medal of Science. Dr. Langer has served as both the chair and a member of the highest advisory board to the U.S. Food and Drug Administration.

A pioneer in the field of tissue engineering, Dr. Langer developed Neuro-Spinal Scaffold^TM to promote regeneration of nerve cells in injured spinal cords. He then co-founded InVivo Therapeutics to advance the scaffold through clinical testing. Dr. Langer also sits on InVivo’s Scientific Advisory Board.

We asked Dr. Langer about the discoveries that led to the scaffold’s development and his vision for building on the device in the future.

---

You are widely regarded as one of the founders of tissue engineering and regenerative medicine. What was your inspiration for resorbable polymers as surgically implanted therapies?

I’ve always been interested in the possibility of using biomaterials to solve challenging medical and surgical problems. My goal has been to leverage innovation in this field to make the biggest impact possible.

In the early 1980s, a friend (Jay Vacanti) and I had the idea of creating 3D organs from synthetic polymers to help keep babies alive while waiting for liver transplants. From my early work, I became fascinated with polymers and their potential to address a wide range of medical problems. Initially our target was the liver, but from there, we began to explore many other potential applications. We could use the polymers to help support other organs, muscle tissue and even blood vessels. Some polymers could even be used as artificial skin to help burn victims heal.

Along the way, we hit upon the idea that perhaps the right polymers could become a scaffold to bridge the cavity that develops in the spine shortly after a spinal cord injury. Neurons can’t transmit signals across that cavity, which is why patients with this type of injury become paralyzed: The signals from their brain cannot reach their arms and legs. We were interested in whether we could design a polymer that would encourage cells to grow in that cavity – and ultimately, remodel the tissue in a way that might preserve the spinal cord’s ability to transmit at least some signals from the brain. That idea became InVivo’s Neural Spinal Scaffold.

In some ways the inspiration behind our 3D scaffold structures was drawn from seaweed– we designed our polymer system based on the porous interweaving patterns you see in seaweed.

I’ve always been interested in the possibility of using biomaterials to solve challenging medical and surgical problems. My goal has been to leverage innovation in this field to make the biggest impact possible.

Why are scaffolds so well suited for the treatment of spinal cord injuries?

The scaffold is designed to provide the structural stability necessary to allow repair to take place. Basically, we hope it will give the body the jump start it needs. Once the scaffold has done its job, we expect it will be safely resorbed into the body.

The Neuro-Spinal Scaffold consists of two biocompatible polymers: PLGA (Polylactic-co-glycolic acid) provides the support and PLL (Poly-L-Lysine) promotes cellular attachment. Together these two polymers form a strong and highly porous structure that is conducive to cellular attachment and neurite outgrowth.

The original idea for the scaffold was to be a ‘bridge’ you could implant within the injured site to help cells repave the damaged spinal cord area. Our thinking was that it would close the gap like a band-aid and promote cellular regrowth. And it did perform better than control surgery without a scaffold; in animal models, we saw less scar tissue and less open space around the injury site in those treated with the scaffold.

What are potential future applications for polymers and scaffolds in the spinal cord injury field?

There is a lot of room for innovation in the spinal cord injury field. We have been investigating applying stem cells to the scaffold before it’s implanted in the patient, for instance. In preclinical studies, we are beginning to see that adding stem cells in this manner may aid in the development of certain nerve connections.

We also hope to investigate applying certain enzymes to the scaffold; we believe they may help remove scar tissue which could enable more direct access for growth factors to repair damaged nerves to help with limb mobility. We could even add controlled-release growth factors to the scaffold. We’re excited to explore these opportunities for both acute and chronic spinal cord injury.

In general, the whole area of tissue engineering is a great opportunity for biomedical innovation, as there are so many conditions that a drug alone won’t help. To a lot of people who reviewed our grant applications in 1980, this sounded like science fiction — but we have come a long way toward making it a reality in 2020.

A Q&A with neurological surgeon and spinal cord researcher James Guest, M.D., Ph.D.

James Guest, M.D., Ph.D., FACS has dedicated his career to the treatment of spinal cord injury and has made significant contributions to the field.

A Professor of Neurological Surgery at the Miller School of Medicine and the Miami Project to Cure Paralysis, he has authored more than 75 peer-reviewed publications, many of them focused on cellular therapy for spinal cord injury. He has also been actively involved in promoting innovative clinical trial design and the progress of essential data registries, including as an investigator for the North American Clinical Trials Network for the Treatment of Spinal Cord Injury.

 Dr. Guest is a member of the Scientific Advisory Board for InVivo Therapeutics, which is developing the Neuro-Spinal Scaffold^TM for the treatment of acute spinal cord injury. We asked him about the current standard of care for spinal cord injury patients – and the potential for future improvements.

---

How do you define success in treating spinal cord injury?

Our concept of success has matured through experience and new knowledge.

We used to prioritize getting people to walk again. Now we also think about successes as helping people regain control of functions regulated by the autonomic nervous system, such as bowel, bladder and sexual function. We think about better cardiovascular control, and reducing the risk of complications such as metabolic syndrome, which is a cluster of conditions including high blood pressure and high blood sugar that together increase the risk of heart disease, type 2 diabetes and impaired brain function.

If we can improve regulation of the autonomic functions and reduce the risk of additional health complications, we can significantly increase quality of life. That’s a success.

Patient-reported outcomes are also very important to the success question. What does a person with the spinal cord injury think is success? Questionnaire responses from the spinal cord injury community have articulated their priorities. Recovery of hand function was the number one priority, then recovery of bowel, bladder and sexual function. Walking — was ranked third.

Is this type of success common?

We do see early successes – but we need to see them more widely, across more people.

Some of the variability in recovery is linked to the acute care. For example, the spinal cord should be completely decompressed so that the spinal fluid can move easily up and down the spine. But we don’t have a standard, either during or after the surgery, to evaluate how well we are decompressing the spine. If it’s not sufficiently decompressed, the opportunity for neurological recovery may be reduced.

Another issue is the quality and intensity of rehabilitation. Some patients go to state-of-the-art facilities after their acute care; others go to nursing homes with very minimal rehabilitation opportunities. That’s a large-scale problem as well.

Based on these examples, there is considerable room for improvement in the treatment of spinal cord injury.

How can InVivo’s Neuro-Spinal Scaffold potentially aid in the treatment of spinal cord injury?

The testing of the Neuro-Spinal Scaffold represents a major innovation in the potential treatment of spinal cord injuries and has been an important step in our field.

The idea with this scaffold is to treat severe injuries by opening up the damaged portion of the spinal cord and allowing the dead tissue to come out. That space is where the scaffold is inserted.

The highly porous scaffold leads to formation of a “neuropermissive matrix” that may improve the healing of the damaged cord. It is designed so that new cells settle in and grow during the repair process.

The testing of the Neuro-Spinal Scaffold represents a major innovation in the potential treatment of spinal cord injuries and has been a very important step in our field.

Is there potential to seed the scaffold with cells before inserting it into the patient?

When you put cells into the spinal cord without a scaffold a number of things can happen. Some cells might not survive, others migrate away, others may stay where they were implanted but fail to integrate into the spinal cord circuitry.

The introduction of cells along with a scaffold could have advantages if certain consequences occur. First, if the cells implanted with the matrix organized in a linear manner that traversed the injury site, nerve fiber regrowth could be improved.

Secondly, innovations of scaffolds could increase the likelihood of the cells’ survival. In this way, the scaffold could serve as a drug delivery tool. Even if the cells did not organize linearly, cells may attach to the scaffold and release various compounds into the damaged area of the spinal cord, which could promote healing. One application is to use the scaffold to release drugs that modify inflammation at the site of injury.

What is most exciting in terms of future treatment options with the scaffold?

The Neuro-Spinal Scaffold that InVivo has developed is a first-generation product. It came out of Bob Langer’s lab at MIT, and that’s a highly innovative group.

As the experience with the Neuro-Spinal Scaffold increases, I’m hopeful that there will be future iterations. There’s a lot of excellent research going on now to enhance the potential of biocompatible scaffolds. I see considerable potential for advancement as the scaffolds to combine therapeutics are developed.