Giving Breakthroughs Their Big Break

How research universities are finding new ways to bring ideas from lab to life

When potentially game-changing medical discoveries don't fit easily into a standard business model, they can languish in a netherworld of limbo known as the Valley of Death. The term refers to the gap between a drug or medical device that holds promise for patients and the resources required to bring it to market. Recognizing their responsibility to improve lives even when profits prove uncertain, universities have begun to identify unconventional ways to advance innovations that could serve society.

Jen French is one of the lucky ones. A longtime athlete, she still competes in outdoor adventures despite the spinal cord injury she sustained in a 1998 snowboarding accident that left her arms and legs paralyzed. Thanks to an electrical-implant system, she continues to sail, ski and scuba dive—all while maintaining a successful career as a nonprofit executive.

The problem? She's among only a handful of patients to have access to this transformational technology, which she received as a participant in a federal research project.

Estimates show about 1.3 million Americans are paralyzed due to spinal cord injury. The number looks sizable, until you consider figures for some common conditions: Heart disease and diabetes each affect more than 33 million people; more than 29 million men have erectile dysfunction; and more than 18 million people are afflicted with cancer.

Medical research is a lengthy and costly enterprise, and business investment in the field represents a gamble under even the best of circumstances. When it comes to research on solutions for spinal cord injuries and other such "smaller market" conditions, treatments promise modest profit at best—particularly when compared with the audience for, say, Viagra.

It's not that French's device and others like it wouldn't benefit patients immensely. Rather, investors prefer the seemingly safer bets on solutions that can affect many more people. A population exists for these innovations—companies simply find it too tiny to be lucrative.

"Sometimes, commercialization is not possible through conventional for-profit channels," says Case Western Reserve University biomedical engineer P. Hunter Peckham, PhD, who heads the Cleveland Functional Electrical Stimulation Center, a multi-institutional collaboration where researchers developed French's device and other technologies that restore function in paralyzed individuals. "In these cases, alternatives must be identified based on a social responsibility to carry medical products through the Valley of Death."

The valley he refers to is a dangerous gap that threatens to swallow scientific advances that stumble along the path to traditional commercialization, usually for lack of funds.

Medical companies easily spend hundreds of millions of dollars navigating rounds of clinical trials, safety studies and federal approvals to release a single medication. When the patient population is sizable, executives can rationalize the investment as an opportunity to reap major returns, and perhaps offset a few attempts that miss the mark. When the numbers don't add up to obvious profit, investors aren't as easily convinced, and the discovery falls into the cracks, often never to be heard from again.

Peckham and his colleagues understand such financial formulas, but find they fall short compared with patients and families desperate for answers. As a result, he and a handful of like-minded scientists across the country have begun to pursue new approaches to increase opportunities to help patients, no matter how few their numbers, to get the drugs and devices they need.

Risky Business

It's a problem of risk versus reward, explains Kevin Grimes, MD, co-director of Stanford University School of Medicine's SPARK program, an initiative designed to move therapies from laboratory benches to human trials. "In medical research and development, a lot of risk is involved. Will the target bear fruit in the form of a new treatment approach that's commercially viable?"

The number of new medical treatments available is halting at best. With new Food and Drug Administration approaches in place, the number of new drug approvals has risen recently, 35 in fiscal year 2011, the second-highest in 10 years, but the great majority of laboratory findings never make it to late-phase trials and FDA review.

The numbers are "mind-boggling," by the description of Chris Hempel, a patient advocate and mother of 8-year-old twin daughters with the rare disease Niemann- Pick Type C. The cholesterol condition has been dubbed "childhood Alzheimer's" for its ruinous effects on young minds. It has been conspicuously short on research attention and funding, as it only affects about 500 patients. Hempel says her girls, Addi and Cassi, would be lucky to live beyond their teenage years if an effective treatment isn't found soon.

"All this money is being pumped into medical research, 800,000 research papers published in a recent year," Hempel says. "We want to see results translated into therapies, and hope, for people."

Part of the problem is that translational research, which advances a basic science finding to the point of justifying clinical trials, is expensive. Such an investment can reach 12 years and hundreds of millions of dollars, according to studies cited by the National Institutes of Health. And the failure rate is high; at least 80 percent of research projects never reach the human trials phase.

"Science, in all its complexity, turns out lots of possibilities, of which only a few will translate," says Robert Miller, PhD, the vice president for research at Case Western Reserve and director of the medical school's Center for Translational Neuroscience.

Given this uncertainty and expense, the medical industry and venture investors often hold off on funding even the most promising-sounding medical developments until later in the clinical development pipeline, when potential for profit is better understood. By this time, though, the Valley of Death has devoured a number of would-be innovations that investors weren't willing to take a risk on.

Emerging Models

Foundations, long a mainstay of nonprofit investment, are among the institutions at the heart of the push for translational research. The Myelin Repair Foundation, an organization committed to finding therapies for multiple sclerosis, for example, is focusing squarely on stopping potential cures from getting lost in what it calls the "black hole" of scientific research. In stark contrast to the normal scientific paradigm, in which basic science researchers can harbor findings for months or years until their papers are published, the organization's band of scientific experts share their discoveries immediately. In fact, Miller has received substantial funding from the foundation for his translational work on MS.

Recently, universities and the federal government, the NIH, in particular, have updated their research philosophies to get in the translation game. Rather than solely focusing on the basic study of underlying human biology, organizations are instead emphasizing a commitment to "de-risk" projects by collecting evidence of safety and effectiveness until private industry feels justified in taking over the reins.

Academic institutions also are playing a growing role in progressing therapeutic concepts.

"Universities are increasingly coming to understand their responsibility to participate in moving their discoveries into the community," Miller says. "To that end, we're taking steps to increase opportunities for interested scientists to translate their findings."

Contracts for collaborations between School of Medicine researchers and industry partners have been updated to ensure fair sharing of revenues, with hopes of attracting more for-profit partners, he explains.

Also, Case Western Reserve has an active team of technology transfer experts who work with faculty to determine whether their ideas have market potential, and help them find funding. This year the School of Medicine supplemented those efforts by recruiting chief translational officers to identify promising work even earlier, and then help shepherd concepts through to market.

At the same time, the NIH has been taking aim at the perilous journey from research to real-life. One such NIH component, the Therapeutics for Rare and Neglected Diseases (TRND) program, studies drugs for conditions that are rare, defined by the Orphan Drug Act of 1983 as affecting fewer than 200,000 Americans, and those that have been overlooked because they affect the world's poorest populations. A huge majority of the 7,000 human diseases fall into one of these two categories, according to the NIH; fewer than 300 of them have the prevalence and commercial promise to generate interest from industry.

"We're situated to take on risks that companies might not consider warranted based on their financial bottom line," says TRND's John McKew, PhD. "We also have the knowledge base to guide scientists through the complexities of preclinical work."

TRND teams experts in translational research with scientists whose basic research shows great promise, thereby supporting researchers, who might lack the specialized knowledge on intellectual property and other sometimes confounding issues, through the process of translation. By collaborating with the NIH, McKew says, academic scientists have the chance to help patients in need, while still securing grants and publishing their research in professional journals.

Rare Chance

Niemann-Pick Type C was among TRND's first areas of focus after the program's 2009 launch. Today the FDA is working on a clinical trial for a sugar molecule that represents the best current hope for a cure.

Patient advocate Hempel says her girls are participating in the study and already have shown improvement. "Today, they're much more alert and are getting their hearing back where they were going deaf before," she says.

As for Jen French, she laments her function-restoring technology hasn't become more widely available, but as a patient advocate, she understands all too well the barriers keeping others from enjoying the abilities she has regained.

After all, she walked down the aisle on her wedding day, and this summer she will take the helm of a two-person SKUD-18 sailboat during the 2012 Paralympic Games in London.

"In the 14 years since I was injured, I've seen a lot of fantastic technologies developed in the world that have never gotten out to the people for whom they were intended," she says.

Until a time comes when funding can make devices like hers mainstays, French will remain one of the lucky few.