2007

The 2007 BMEidea Winners: 1.5 years later

The third round of BMEidea competition winners featured technologies with the potential to revolutionize how we deliver vaccines, how we treat Parkinson's disease and how we repair peripheral nerve injuries. We caught up with the teams a year and a half after the competition to see what they were up to, how their projects were going, and how participating in the BMEidea competition influenced their careers.
 

First prize: Rotavirus Vaccination via Oral Thin Film Delivery, Johns Hopkins University 

A big part of innovation is thinking about problems in a different way. Changing your point of reference can lead to creativity, and creativity can lead to originality.

An example is the Rotavirus Vaccination team from Johns Hopkins University, winner of the 2007 BMEidea competition. Rotavirus, a disease that causes severe diarrhea and vomiting in children, kills 600,000 people in the developing world each year. While there is a vaccine for the disease, few children in the developing world end up getting it due to problems with cold chain storage: the vaccine has to be kept refrigerated, often an impossibility in rural areas where refrigeration is scarce. 

The innovative solution? Change the vaccine itself. While the liquid form of rotavirus vaccine requires refrigeration, the Johns Hopkins team is developing a dry form derived from thin film technology, similar to Listerine's quick-dissolving breath strips. The team's dissolvable strip is seeded with the vaccine, then coated with a special material to protect it in the child's stomach. That same coating disintegrates in the small intestine, releasing the vaccine, triggering an immune response and preventing future infection. All on a little strip that requires no refrigeration and is light and easy to ship.

The Rotavirus project began at Aridis Pharmaceuticals, a San Jose firm that invented a rotavirus vaccine stable at room temperatures. Aridis approached Johns Hopkins professor Hai-Quan Mao about coming up with a drug delivery vehicle for its novel vaccine. Mao brought the challenge to one of his undergraduate lab assistants, Chris Yu, who became co-leader of the team that tackled the project.

They faced several obstacles right out of the chute. For one, they couldn't copy the manufacturing process that Listerine uses to make breath strips, since the harsh solvents and high temperatures it requires ended up destroying the live vaccine. They also had to devise a protective coating that would remain intact when exposed to stomach acid but dissolve in the small intestine. Said Yu, "Our technology is geared toward delivering a live attenuated virus for a vaccine, not just freshening breath. We quickly found out that in order to get it to work, we'd need to take a different approach--use more advanced technology.

They got through the challenges with hard work and research. They developed a room-temperature production and drying process to fabricate the strips and identified an FDA-approved biocompatible polymer coating that would protect the vaccine in the stomach and release it in the small intestine.

Much more work remains before the vaccine is a finished product, however. Since winning BMEidea funding the team has continued research. And while most of the team has graduated and moved on, Yu is remaining on the project while pursuing his masters at Johns Hopkins. "Aridis is still very interested in the product, of course," said Yu. "They're very happy with our progress, and have hired a post-doc to work with me in the lab."

"The foundation of the system has already been laid: how we're going to deliver the vaccine to the small intestine, what kind of release profile it will have. Now we need to optimize the system. We need to optimize the film formulation, and ultimately add as many components as possible to make it easy to ship and make sure it's easy to use for inexperienced healthcare providers."

Yu is honest about the biggest benefit of winning the BMEidea competition: the money helps. "NCIIA has given us a lot of the financial backing for what we're doing. A lot of the components that are needed to formulate and test our design are actually quite expensive. We wouldn't be as far along as we are without the funding."

Beyond that, Yu says that participating in BMEidea gave him a better grasp of the business issues surrounding rotavirus. "Even though the rotavirus vaccine is abundant in the US, virtually none of it is making it to developing countries that need it," he said. "Science aside, the business end of this project--getting the vaccine into the hands of people who need it--is extremely important and will need to be addressed as soon as our prototype is ready to go."
 

Second prize: enLight: Enabling Life with Light, Stanford University

Parkinson's disease is a degenerative central nervous system disorder that causes a breakdown in muscle function and speech. The disease affects 1.5 million patients in the US alone--a number that will likely rise as the population ages--yet there remains no definitive treatment for PD. Current therapies run the gamut from drugs to surgery all the way to qigong, a traditional Chinese breathing exercise.

One of the most promising new approaches to treating PD is deep brain stimulation (DBS). Since a main factor involved in causing Parkinson's is the insufficient formation and action of dopamine, DBS involves placing an electrode deep within the brain to stimulate the parts of the brain responsible for dopamine production. DBS has been shown to alleviate some of the motor tremors in Parkinson's patients and can lead to an improvement in quality of life. 

The drawback? DBS is only effective in a very small percentage of PD patients (~5%) because electrode-based stimulation is highly nonspecific. During DBS, many more brain cells other than those responsible for PD pathology are stimulated, which can lead to a number of severe side effects including apathy, hallucinations, compulsive gambling, hypersexuality, cognitive dysfunction and depression. Clearly there is a need for a better device--one that can specifically target only the neurons involved in PD, lessening the side effects.

This Stanford University team, winner of second place in the 2007 BMEidea competition, believes it's found the solution. The team is developing enLight, a remarkably forward-thinking, novel treatment for PD that enables the effective and reliable control of neural activity using light.

Here's how it works: instead of implanting an electrode, the team implants a thin optic fiber in the brain. Then, using gene therapy techniques, they introduce a genetically coded protein that makes the neurons specifically involved in Parkinson's sensitive to light. The optic fiber shines light into the right region of the brain, and voila, only the neurons associated with Parkinson's are activated. The ability to directly and specifically control neurons represents a major step forward and has the potential to revolutionize the field.

It all started with algae--or, more specifically, the algae-related lab work of Feng Zhang, a graduate student at Stanford. "When I first joined the lab in January 2005," says Zhang, "I started working on technology that would allow you to take protein from green algae and transfer it to neurons to make them light sensitive. Algae have light-sensitive neurons that they use to find sunlight for photosynthesis; by transferring this algal protein into animal neurons we figured we would be able to very precisely control neural firing."

Zhang was right. After establishing the validity of the technology, his team started developing genetic techniques that would allow them introduce the protein into specific neurons. They do this through lentiviruses, a genus of viruses that can deliver a significant amount of genetic information into the DNA of a host cell. Thus the biological basis of the technology was formed.

Soon enough they began to think about ways to use the technology for therapeutic purposes, and hit upon Parkinson's as the most likely first target. "We looked into diseases that could be treated using our approach, and, largely because of the body of research that has already been formed on Parkinson's and deep brain stimulation, we chose Parkinson's."

The team has made solid progress since winning BMEidea funding, filing several patents and moving toward pre-clinical animal testing. According to Zhang, the next steps are getting the biological reagent produced and ramping up to clinical trials. On the device side, refinements need to be made to the optical fiber "to make sure we're bringing in enough light, but not too much light. It's a tough technical challenge."

Other challenges involve finding the right animal model to use for testing, and making sure their virus doesn't cause damage to the brain--that it infects the right neurons. But despite all the obstacles to overcome, Zhang sees this product hitting the market in five to eight years, and making a big impact.

As far as the impact of winning BMEidea is concerned, Zhang strikes a familiar chord: winning gave his project credibility. "First of all it gave us validation--maybe our idea isn't so crazy after all!" he said. "Plus the events that we've attended as a result of winning BMEidea have been very helpful. I've been able to network with people who work in the medical device industry and gotten insight on basic things, like how to think about medical devices, how to manufacture a device, etc. They were very helpful."
 

Third prize: Bioactive Nanopatterned Grafts for Nerve Regeneration, University of California, Berkeley

Peripheral nerves are the extensive network of nerves outside the brain and spinal cord. Like static on a telephone line, peripheral nerve injuries distort or interrupt the messages between the brain and the rest of the body, affecting a person's ability to move or feel normal sensations. This is a common problem affecting about 800,000 Americans each year.

The gold standard approach to fixing it is the nerve autograft--removing a segment of nerve from one part of the body and suturing it in place at the site of injury. While this is effective in some cases, the approach comes with a number of risks and drawbacks: the donor nerves tend to be small, usually requiring the doctor to stack a bunch of them together to make an implantable graft; two invasive surgeries are required, one for harvesting the donor nerves and one for implanting them; sometimes the graft simply doesn't work; some patients don't have any nerves suitable for donation; and the donor site can react badly, causing more pain than the nerve injury itself.

A different approach to the problem gaining in popularity is the world of synthetic grafts. Made of various polymers wrapped into a sturdy tube shape, a handful of grafts are currently on the market. But the current designs come with limitations as well: none can outperform the nerve autograft in clinical trials, they don't provide cues for regeneration the way a normal nerve would, and they can't bridge gaps longer than four centimeters. There is a clinical need for a synthetic graft that better mimics the nerve autograft and has the ability to regenerate damaged nerves of all sizes, and this UC Berkeley team is looking to provide it.

The team, winner of third place in the 2007 BMEidea competition and now incorporated as NanoNerve, is developing a novel synthetic graft that enhances and guides nerve regeneration across a range of peripheral nerve injuries. The tubular graft is composed entirely of nanoscale polymer fibers loaded with bioactive molecules that provide growth cues for regenerating. The technology is also capable of spanning large gaps.

Altogether, this makes a product that is "simply better than what's out there," according to team leader Shyam Patel. "We can heal longer nerve injuries, we can provide growth cues, and we'll be proving that through human trials taking place next year."

The key to the technology has to do with how the grafts are fabricated. The most common method of fabricating polymer nanofibers is to use an electrical field to "spin" very thin fibers. This technique, called electrospinning, can be used to make nanofiber scaffolds in various shapes. The key innovation allows the team to fabricate grafts composed entirely of nanofibers aligned along the length of the tubes, allowing for customization of the length, diameter and thickness of the grafts. Combine that innovation with a way to make the nanofibers bioactive by attaching chemicals directly to the surface, and you've got a technology that mimics the nerve autograft by providing both physical and biochemical cues to direct nerve growth.

Armed with a potential breakthrough technology, things are moving quickly for NanoNerve. After graduating from Berkeley, Patel and a handful of others licensed the technology from the university and formed the company around it. They're currently in the development phase of the product, but according to Patel they're "actually very far along in the process. We hope to file for FDA 510k clearance by the end of the year, which will allow us to start marketing the product in 2009."

Assuming all goes well in human clinical trials, Patel sees NanoNerve taking off. "We'll be able to sell the product as something that is functionally better than what's currently available, something that will serve as an effective alternative to the autograft. Our technology takes full advantage of the fact that the shortest distance between damaged nerve endings is a straight line. It directs straightforward nerve growth and never lets them stray from the fast lane."

NanoNerve may very well be in the fast lane itself. And according to Patel, participating in the BMEidea competition has helped put it there. "The press and publicity as a result of winning third in BMEidea was very helpful in terms of getting the word out about what we're doing," he said. "It's helped the company since it shows that the project has scientific merit, shows that is has value to the medical community. It's helped us impress the people we've been talking to about it and has definitely validated what we're trying to do."