Stem cells and professional sports: a call for more science and less speculation

In the world of professional sports, teams invest tens of millions of dollars in players. Those players are under intense pressure to show a return on that investment for the team, and that means playing as hard as possible for as long as possible. So it’s no surprise that players facing serious injuries will often turn to any treatment that might get them back in the game.

image courtesy Scientific American

image courtesy Scientific American

A new study published last week in 2014 World Stem Cell Report (we blogged about it here) highlighted how far some players will go to keep playing, saying at least 12 NFL players have undergone unproven stem cell treatments in the last five years. A session at the recent World Stem Cell Summit in San Antonio, Texas showed that football is not unique, that this is a trend in all professional sports.

Dr. Shane Shapiro, an orthopedic surgeon at the Mayo Clinic, says it was an article in the New York Times in 2009 about two of the NFL players named in the World Stem Cell Report that led him to becoming interested in stem cells. The article focused on two members of the Pittsburgh Steelers team who were able to overcome injuries and play in the Super Bowl after undergoing stem cell treatment, although there was no direct evidence the stem cells caused the improvement.

“The next day, the day after the article appeared, I had multiple patients in my office with copies of the New York Times asking if I could perform the same procedure on them.”

Dr. Shapiro had experienced what has since become one of the driving factors behind many people seeking stem cell therapies, even ones that are unproven; the media reports high profile athletes getting a treatment that seems to work leading many non-athletes to want the same.

“This is not just about high profile athletes it’s also about older patients, weekend warriors and all those with degenerative joint disease, which affects around 50 million Americans. Currently for a lot of these degenerative conditions we don’t have many good non- surgical options, basically physical therapy, gentle pain relievers or steroid injections. That’s it. We have to get somewhere where we have options to slow down this trend, to slow down the progression of these injuries and problems.”

Shapiro says one of the most popular stem cell-based approaches in sports medicine today is the use of plasma rich platelets or PRP. The idea behind it makes sense, at least in theory. Blood contains platelets that contain growth factors that have been shown to help tissue heal. So injecting a patient’s platelets into the injury site might speed recovery and, because it’s the patient’s own platelets, the treatment probably won’t cause any immune response or prove to be harmful.

That’s the theory. The problem is few well-designed clinical trials have been done to see if that’s actually the case. Shapiro talked about one relatively small, non-randomized study that used PRP and in a 14-month follow-up found that 83% of patients reported feeling satisfied with their pain relief. However, 84% of this group did not have any visible improved appearance on ultrasound.

He is now in the process of carrying out a clinical trial, approved by the Food and Drug Administration (FDA), using bone marrow aspirate concentrate (BMAC) cells harvested from the patient’s own bone marrow. Because those cells secrete growth factors such as cytokines and chemokines they hope they may have anti-inflammatory and regenerative properties. The cells will be injected into 25 patients, all of whom have arthritic knees. They hope to have results next year.

Dr. Paul Saenz is a sports medicine specialist and the team physician for the San Antonio Spurs, the current National Basketball Association champions. He says that sports teams are frequently criticized for allowing players to undergo unproven stem cell treatments but he says it’s unrealistic to expect teams to do clinical studies to see if these therapies work, that’s not their area of expertise. But he also says team physicians are very careful in what they are willing to try.

“As fervent as we are to help bring an athlete back to form, we are equally fervent in our desire not to harm a $10 million athlete. Sports physicians are very conservative and for them stem cells are never the first thing they try, they are options when other approaches have failed.”

Saenz said while there are not enough double blind, randomized controlled clinical trials he has seen many individual cases, anecdotal evidence, where the use of stem cells has made a big difference. He talked about one basketball player, a 13-year NBA veteran, who was experiencing pain and mobility problems with his knee. He put the player on a biologic regimen and performed a PRP procedure on the knee.

“What we saw over the next few years was decreased pain, and a dramatic decrease in his reliance on non-steroidal anti inflammatory drugs. We saw improved MRI findings, improved athletic performance with more time on court, more baskets and more rebounds.”

But Saenz acknowledges that for the field to advance anecdotal stories like this are not enough, well-designed clinical trials are needed. He says right now there is too much guesswork in treatments, that there is not even any agreement on best practices or standardized treatment protocols.

Dr. Shapiro says for too long the use of stem cells in sports medicine has been the realm of individual physicians or medical groups. That has to change:

“If we are ever to move forward on this it has to be opened up to the scientific community, we have to do the work, do the studies, complete the analysis, open it up to our peers, report it in a reputable journal. If we want to treat the 50 million Americans who need this kind of therapy we need to go through the FDA approval process. We can’t just continue to treat the one patient a month who can afford to pay for all this themselves. “

World Stem Cell Summit: The environment stem cells find themselves in after transplant really matters

On Friday’s closing day of the 2014 World Stem Cell Summit a panel of three researchers working on neurodegenerative diseases drove home the importance of paying attention to the environment that surrounds stem cells after transplant.

world-stem-cells-summit-2014

CIRM grantee Evan Snyder from the Sanford-Burnham Institute noted that most of the neurologic diseases people are looking at are conditions associated with aging and the cellular makeup of the brain changes as we get older, adding that most of the diseases result from chronic states that have existed over many years. He contrasted this against mouse models of the disease, which usually involve artificially recreating the disease and treating shortly after the injury happens.

“In stem cell therapies there is a dialogue between the transplanted cells and the recipient. The host influences the fate of the stem cells.”

He noted that the patients we will be treating have generally had long-term degeneration and asked if we might be able to develop drugs that effect the environment where the stem cells will be placed so that it mimics more closely the environment found in the animal model in the acute phase, that is right after injury.

One aspect of the environment in the brain in most patients with neurodegeneration is chronic inflammation. Another CIRM grantee on the panel, Jeanne Loring of the Scripps Research Institute, discussed a project her team hopes will take advantage of the inflammation that occurs in Alzheimer’s disease. They are loading nerve stem cells with an enzyme that can degrade the plaque that accumulates in nerves in the disease. Because stem cells home to inflammation, they hypothesize that the stem cells will be drawn to deliver their cargo to the nerves with the worst plaque.

The third panelist, Erzi Kokovay of the University of Texas Health Science Center in San Antonio, described the changes in the brain as we age in a bit more detail. She described infiltration of cells called microglia that researchers will need to take into account when they plan to transplant stem cells in the brain.

While on the surface this all may sound like another road block to getting to the stem cell cures we all want, the presentation actually made me optimistic that we are starting to learn enough about the field that we are more likely to get it right when we start to treat some of these devastating brain diseases.

Don Gibbons

Taking Promising Therapies out of the Lab and into People: Tips from Experts at the World Stem Cell Summit on How to Succeed

Having a great idea for a stem cell therapy is the easy part. Getting it to work in the lab is tougher. But sometimes the toughest part of all is getting it out of the lab and into clinical trials in patients. That’s natural and sensible, after all we need to make sure that something seems safe before even trying it in people. But how do you overcome all the challenges you face along the way? That was the topic of one of the panel discussions at the World Stem Cell Summit in San Antonio, Texas.

Rick Blume is the Managing Director at Excel Venture Management, and someone with decades of experience in investing in healthcare companies. He says researchers face numerous hurdles in trying to move even the most promising therapies through the approval and regulatory process, only some of which are medical. Blume says:

“Great ideas can become great companies. And good Venture Capitalists (VCs) can help with that process, but the researchers have to overcome technical, funding and logistical hurdles before VCs are usually ready to move in and help.”

Of course that’s where agencies and organizations like CIRM come in. We help fund the early stage research, helping researchers overcome those hurdles and getting promising therapies to a point where VCs and other large investors are willing to step in.

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Geoff Crouse, the CEO of the Cord Blood Registry, says researchers need to be increasingly imaginative when looking for funding these days.

“While Federal funding for this kind of research is drying up, there are alternatives such as CIRM and philanthropic investors who are not just seeking to make active investments but are also trying to change the world, so they offer alternatives to more traditional sources of funding. You have to look broadly at your funding opportunities and see what you want to do.”

C. Randal Mills, the President and CEO of CIRM said too many people get caught up looking at the number of challenges that any project faces when it starts out:

“The single most important thing that you need to do is to show that the treatment works in people with unmet medical needs, that it is safe. If you can do that, all the other problems, the cost of the therapy, how to market it, how to get reimbursed for it, those will all be resolved in time. But first you have to make it work, then you can make it work better and more efficiently.”

The panel all agreed that one of the areas that needs attention is the approval and regulatory process saying the Food and Drug Administration (FDA) the regulatory body governing this field, needs to adjust its basic “one size fits all” paradigm.”

Mills says the FDA is in a difficult position:

“Everyone wants three things; they want fast drugs, they want cheap drugs and they want perfect drugs. The problem is you can’t have all three. You can have two but not all three and that puts the FDA into an almost impossible position because if therapies aren’t approved quickly they are criticized but if they are approved and later show problems then the FDA is criticized again.”

Often the easiest way to get a traditional drug therapy approved for use is to ask for a “humanitarian exemption”, particularly for an orphan disease that has a relatively small number of people suffering from it and no alternative therapies. But when it comes to more complex products knows as biologics, which includes stem cell therapies, this humanitarian exemption does not exist making approval much harder to obtain, slowing down the field.

Mills says other countries, such as Japan, have made adjustments to the way they regulate new therapies such as stem cells and he hopes the FDA will learn from that and make similar modifications to the way they see these therapies.

All three panelists were optimistic that the field is making good progress, and will continue to advance. Good news for the many patient advocates attending the World Stem Cell Summit who are waiting for treatments for themselves or loved ones.

At World Stem Cell Summit: Why results in trials repairing hearts are so uneven

Just as no two people are the same, neither are the cells in their bone marrow, the most common source of stem cells in clinical trials trying to repair damage after a heart attack. Doris Taylor of the Texas Heart Institute in Houston, which is just a couple hours drive from the site of this year’s World Stem Cell Summit in San Antonio, gave a key note address this morning that offered some good reasons for the variable and often disappointing results in those trials, as well as some ways to improve on those results.

THI's Dr. Doris Taylor

THI’s Dr. Doris Taylor

The cells given in a transplant derived from the patient’s own bone marrow contain just a few percent stem cells and a mix of adult cells, but for both the stem and adult cells the mix is highly variable. Taylor said that in essence we are giving each patient a different drug. She discussed a series of early clinical trials in which cell samples from each patient were banked at the National Heart and Lung and Blood Institute. There they could do genetic and other analysis on the cells and compare that data with how each individual patient faired.

In looking at the few patients in each trial that did better on any one of three measures of improved heart function, they were indeed able to find certain markers that predicted better outcome. In particular they looked at “triple responders,” those who improved in all three measures of heart function. They found there were both certain types of adult cells and certain types of stem cells that seemed to result in improved heart health.

They also found that two of the strongest predictors were gender and age. Women generally develop degenerative diseases of aging like heart disease at an older age than men and since many consider aging to be a failure of our adult stem cells, it would make sense that women have healthier stem cells.

Taylor went on to discuss ways to use this knowledge to improve therapy outcomes. One way would be to select for the more potent cells identified in the NHLBI analysis. She mentioned a couple trials that did show better outcomes using cells derived from heart tissue. One of those is work that CIRM funds at Cedars-Sinai in Los Angeles.

Another option is replace the whole heart and she closed with a review of what is probably her best-known work, trying to just that. In rats and pigs, she has taken donor hearts and used soap-like solutions to wash away the living cells so that all that is left behind are the proteins and sugars that make of the matrix between cells. She then repopulates the scaffolds that still have the outlines of the chambers of the heart and the blood vessels that feed them, with cells from the recipient animal. She has achieved partially functional organs but not fully functional ones. She—along with other teams around the world—is working on the remaining hurdles to get a heart suitable for transplant.

Don Gibbons

Taking stock: ten years of the stem cell agency, progress and promise for the future

Under some circumstances ten years can seem like a lifetime. But when lives are at stake, ten years can fly by in a flash.

Ten years ago the people of California created the stem cell agency when they overwhelmingly approved Proposition 71, giving us $3 billion to fund and support stem cell research in the state.

In 2004 stem cell science held enormous potential but the field was still quite young. Back then the biology of the cells was not well understood, and our ability to convert stem cells into other cell types for potential therapies was limited. Today, less than 8 years after we actually started funding research, we have ten projects that are expected to be approved for clinical trials by the end of the year, including work in heart disease and cancer, HIV/AIDS and diabetes. So clearly great progress has been made.

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Yesterday we held an event at the University of Southern California (USC) to mark those ten years, to chart where we have come from, and to look to where we are going. It was a gathering of all those who have, as they say, skin in the game: researchers, patients and patient advocates.

The event was held at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research. As Dr. Carmen Puliafito, Dean of USC’s Keck School of Medicine noted, without CIRM the building would not even exist.

“With this funding, our researchers, and researchers in 11 other facilities throughout the state, gained a dedicated space to hunt for cures for some of the most pernicious diseases in the world, including heart disease, stroke, cancer, diabetes, Alzheimer’s and Parkinson’s disease.”

Dr. Dhruv Sareen from Cedars-Sinai praised CIRM for creating a whole new industry in the state:

“What Silicon Valley has done for technology, CIRM is doing for stem cell research in California.”

One of the beneficiaries of that new industry has been ViaCyte, a San Diego-based company that is now in clinical trials with a small implantable device containing stem cell-derived cells to treat type 1 diabetes. ViaCyte’s Dr. Eugene Brandon said without CIRM none of that would have been possible.

“In 2008 it was extremely hard for a small biotech company to get funding for the kind of work we were doing. Without that support, without that funding from CIRM, I don’t know where this work would be today.”

As with everything we do, at the heart of it are the patients. Fred Lesikar says when he had a massive heart attack and woke up in the hospital his nurse told him about a measure they use to determine the scale of the attack. When he asked how big his attack had been, she replied, “I’ve never seen numbers that large before. Ever.”

Fred told of leaving the hospital a diminished person, unable to do most basic things because his heart had been so badly damaged. But after getting a stem cell-based therapy using his own heart cells he is now as active as ever, something he says doesn’t just affect him.

“It’s not just patients who benefit from these treatments, families do too. It changes the life of the patient, and the lives of all those around them. I feel like I’m back to normal and I’m so grateful for CIRM and Cedars-Sinai for helping me get here.”

The team behind that approach, based at Cedars-Sinai, is now in a much larger clinical trial and we are funding it.

The last word in the event was left to Bob Klein, who led the drive to get Proposition 71 passed and who was the agency’s first Chair. He said looking at what has happened in the last ten years: “it is beyond what I could have imagined.”

Bob noted that the field has not been without its challenges and problems to overcome, and that more challenges and problems almost certainly lie in the future:

“But the genius of the people of this state is reflected in their commitment to this cause, and we should all be eternally grateful for their vision in supporting research that will save and transform people’s lives.”

10 Years/10 Therapies: 10 Years after its Founding CIRM will have 10 Therapies Approved for Clinical Trials

In 2004, when 59 percent of California voters approved the creation of CIRM, our state embarked on an unprecedented experiment: providing concentrated funding to a new, promising area of research. The goal: accelerate the process of getting therapies to patients, especially those with unmet medical needs.

Having 10 potential treatments expected to be approved for clinical trials by the end of this year is no small feat. Indeed, it is viewed by many in the industry as a clear acceleration of the normal pace of discovery. Here are our first 10 treatments to be approved for testing in patients.

HIV/AIDS. The company Calimmune is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease.

Spinal cord injury patient advocate Katie Sharify is optimistic about the latest clinical trial led by Asterias Biotherapeutics.

Spinal cord injury patient advocate Katie Sharify is optimistic about the clinical trial led by Asterias Biotherapeutics.

Spinal Cord Injury. The company Asterias Biotherapeutics uses cells derived from embryonic stem cells to heal the spinal cord at the site of injury. They mature the stem cells into cells called oligodendrocyte precursor cells that are injected at the site of injury where it is hoped they can repair the insulating layer, called myelin, that normally protects the nerves in the spinal cord.

Heart Disease. The company Capricor is using donor cells derived from heart stem cells to treat patients developing heart failure after a heart attack. In early studies the cells appear to reduce scar tissue, promote blood vessel growth and improve heart function.

Solid Tumors. A team at the University of California, Los Angeles, has developed a drug that seeks out and destroys cancer stem cells, which are considered by many to be the reason cancers resist treatment and recur. It is believed that eliminating the cancer stem cells may lead to long-term cures.

Leukemia. A team at the University of California, San Diego, is using a protein called an antibody to target cancer stem cells. The antibody senses and attaches to a protein on the surface of cancer stem cells. That disables the protein, which slows the growth of the leukemia and makes it more vulnerable to other anti-cancer drugs.

Sickle Cell Anemia. A team at the University of California, Los Angeles, is genetically modifying a patient’s own blood stem cells so they will produce a correct version of hemoglobin, the oxygen carrying protein that is mutated in these patients, which causes an abnormal sickle-like shape to the red blood cells. These misshapen cells lead to dangerous blood clots and debilitating pain The genetically modified stem cells will be given back to the patient to create a new sickle cell-free blood supply.

Solid Tumors. A team at Stanford University is using a molecule known as an antibody to target cancer stem cells. This antibody can recognize a protein the cancer stem cells carry on their cell surface. The cancer cells use that protein to evade the component of our immune system that routinely destroys tumors. By disabling this protein the team hopes to empower the body’s own immune system to attack and destroy the cancer stem cells.

Diabetes. The company Viacyte is growing cells in a permeable pouch that when implanted under the skin can sense blood sugar and produce the levels of insulin needed to eliminate the symptoms of diabetes. They start with embryonic stem cells, mature them part way to becoming pancreas tissues and insert them into the permeable pouch. When transplanted in the patient, the cells fully develop into the cells needed for proper metabolism of sugar and restore it to a healthy level.

HIV/AIDS. A team at The City of Hope is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease

Blindness. A team at the University of Southern California is using cells derived from embryonic stem cell and a scaffold to replace cells damaged in Age-related Macular Degeneration (AMD), the leading cause of blindness in the elderly. The therapy starts with embryonic stem cells that have been matured into a type of cell lost in AMD and places them on a single layer synthetic scaffold. This sheet of cells is inserted surgically into the back of the eye to replace the damaged cells that are needed to maintain healthy photoreceptors in the retina.

Spinal cord injury and stem cell research; find out the latest in a Google Hangout

Spinal cord injuries are devastating, leaving the person injured facing a life time of challenges, and placing a huge strain on their family and loved ones who help care for them.

The numbers affected are not small. More than a quarter of a million Americans are living with spinal cord injuries and there are more than 11,000 new cases each year.

It’s not just a devastating injury, it’s also an expensive one. According to the National Spinal Cord Injury Statistical Center it can cost more than $775,000 to care for a patient in the first year after injury, and the estimated lifetime costs due to spinal cord injury can be as high as $3 million.

Right now there is no cure, and treatment options are very limited. We have heard for several years now about stem cell research aimed at helping people with spinal cord injuries, but where is that research and how close are we to testing the most promising approaches in people?

That’s going to be the focus of a Google Hangout on Spinal Cord Injury and Stem Cell Research that we are hosting tomorrow, Tuesday, November 18 from noon till 1pm PST.

We’ll be looking at the latest stem cell-based treatments for spinal cord injury including work being done by Asterias Biotherapeutics, which was recently given approval by the Food and Drug Administration (FDA) to start a clinical trial for spinal cord injury. We are giving Asterias $14.3 million to carry out that trial and you can read more about that work here.

We’re fortunate in having three great guests for the Hangout: Jane Lebkowski, Ph.D., the President of research and development at Asterias; Roman Reed, a patient advocate and tireless champion of stem cell research and the founder of the Roman Reed Foundation; and Kevin Whittlesey, Ph.D., a CIRM science officer, who will discuss other CIRM-funded research that aims to better understand spinal cord injury and to bring stem cell-based therapies to clinic trials.

You can find out how to join the Hangout by clicking on the event page link: http://bit.ly/1sh1Dsm

The event is free and interactive, so you’ll be able to ask questions of our experts. You don’t need a Google+ account to watch the Hangout – just visit the event page at the specified time. If you do have a G+ account, please RSVP at the event page (link shown above). Also, with the G+ account you can ask questions in the comment box on this event page. Otherwise, you can tweet questions using #AskCIRMSCI or email us at info@cirm.ca.gov.

We look forward to seeing you there!

Ideas and Energy Reveal Surprises at Stem Cell Showcase

Janssen, the company within the pharmaceutical giant Johnson & Johnson responsible for much of its research and development, has a branch in the Bay Area called J Labs. It seeks to foster innovation in all sectors of biomedical research. One piece of that effort brings together innovators for monthly gatherings to exchange ideas and network. The events have an upbeat sense of energy so it was exciting when they invited CIRM to put together an all-day session dubbed: CIRM Showcase: Accelerating Stem Cell Treatments to Patients.

logo

The resulting showcase yesterday had that energy. But for someone who knows the CIRM portfolio of projects backward and forward, I thought, there were a few pleasant surprises. Perhaps the most exciting news came from Linda Marban, CEO of Capricor, the company CIRM is funding to complete a clinical trial in patients with weakened hearts after a heart attack. She disclosed that the company’s next target is the heart remodeling that is the cause of death in most boys with Duchenne muscular dystrophy. She said some early data would be released at the American Heart Association meeting in Chicago in two weeks.

Another bit of news—most exciting for science wonks—came from the biotech company Sangamo that CIRM funds to develop genetically modified blood stem cells as therapy for two diseases, HIV and beta thalassemia. The firm has developed a molecular scissors called a zinc finger nuclease that can splice the DNA that makes our genes. I knew the technique was pretty precise, but Curt Herberts from the company said they had perfected it to where it could get down to a single base pair—a single link in the chain that makes up our DNA. This greatly reduces the chances for any unintended effects of the genetic manipulation.

Two advances I learned about were in using iPS type stem cells as models for disease and for discovery of traditional drugs to treat those diseases. Ashkan Javaherian, from Steve Finkbeiner’s lab at the Gladstone Institutes, described some results with the robotic microscope they have developed that lets them screen hundreds of molecules on neurons grown from iPS cells reprogrammed from patients with specific diseases. Looking just at compounds already approved by the Food and Drug Administration (FDA), ones that could be put in the clinic quickly, they found four that reduced the degradation normally seen in neurons grown from patients with Huntington’s disease.

Similarly, Joseph Wu of Stanford described his work with cells from families with various genetic heart disorders. In addition to getting individualized information from the patient-specific cells, he said they could now take it one step further and sequence the entire DNA of the cells for just $500, yielding the chance to find out exactly what mutations were causing the disease. He said it was a big step towards truly personalized medicine and to developing therapies for various racial groups that respond differently to drugs.

The day began with our President and CEO C. Randall Mills detailing his plans for a nimbler, more responsive CIRM he has dubbed CIRM 2.0. This crowd seemed thrilled with his plan for an open call for applications so that they could come in with a request when they are ready instead of forcing them into a premature application for funding because the window might not open for another year or two.

One bit of trivia drove home how difficult the entire process of moving innovative therapies into the clinic can be. Paul Laikind, CEO of ViaCyte, the company CIRM has provided more than $50 million to develop a diabetes therapy, noted the size of the application they sent to the FDA: 8,500 pages. Kind of says it all.

Don Gibbons

Bringing out the Big Guns: Scientists Weigh in on How Best to Combat Deadly Diseases of the Brain

Despite our best efforts, diseases of the brain are on the rise. Neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases threaten not only to devastate our aging population, but also cripple our economy. Meanwhile, the causes of conditions such as autism remain largely unknown. And brain and spinal cord injuries continue to increase—leaving their victims with precious few options for improving their condition.

This special review issue of addresses some of the key challenges for translational neuroscience and the path from bench to beside. [Credit: Cell Press]

This special review issue of Neuron addresses some of the key challenges for translational neuroscience and the path from bench to beside. [Credit: Cell Press]

We need to do better.

The scientific community agrees. And in a special issue of the journal Neuron, the field’s leading researchers lay out how to accelerate much-needed therapies to the many millions who will be affected by brain disease or injury in the coming years.

The journal’s leadership argues that now is the time to renew efforts in this field. Especially worrying, say experts, is the difficulty in translating research breakthroughs into therapies.

But Neuron Editor Katja Brose is optimistic that the answers are out there—we just need to bring them to light:

“There is resounding agreement that we need new approaches and strategies, and there are active efforts, discussion and experimentation aimed at making the process of therapeutic development more efficient and effective.”

Below are three papers highlighted in the special journal, each giving an honest assessment of how far we’ve come, and what we need to do to take the next step.

Fast-tracking Drug Development. In this perspective, authors from the Institute of Medicine (IOM) and the Salk Institute—including CIRM grantee Fred Gage—discuss the main takeaways from an IOM-sponsored workshop aimed at finding new avenues for accelerating treatments for brain diseases to the clinic.

The main conclusion, according to the review’s lead author Steve Hyman, is a crucial cultural shift—various stakeholders in academia, government and industry must stop thinking of themselves as competitors, but instead as allies. Only then will the field be able to successfully shepherd a breakthrough from the lab bench and to the patient’s bedside.

Downsized Divisions’ Dangerous Effects. Next, an international team of neuroscientists focuses their perspective on the recent trend of pharmaceutical companies to cut back on funding for neuroscience research. The reasoning: neurological diseases are far more difficult than other conditions, and proving to be too costly and too time-consuming to be worth continued effort.

The solution, says author Dennis Choi of State University of New York Stonybrook, is a fundamental policy change in the way that market returns of neurological disease drug development are regulated. But Choi argues that such a shift cannot be achieved without a concerted effort by patient advocates and nonprofits to lead the charge. As he explains:

“The broader neuroscience community and patient stakeholders should advocate for the crafting and implementation of these policy changes. Scientific and patient group activism has been successful in keeping the development of therapies in other areas—such as HIV and cancer—appropriately on track, but this type of sector-wide activism would be a novel step for the neuroscience community.”

Indeed, here at CIRM we have long helped support the patient community—a wonderful collection of individuals and organizations advocating for advances in stem cell research. We are humbled and honored that so many patients and patient advocates have stepped forward as stem cell champions as we move towards the clinic.

The Road to Preclinical Diagnosis. Finally, we hear from Harvard University neuroscientists highlighting how far the research has come—even in the face of such extraordinary difficulty.

Specifically focused on Alzheimer’s disease, the authors touch on the discoveries of protein markers, such as amyloid-beta and tau, that serve as an indicator of neurodegeneration. They make the important point that because Alzheimer’s is almost certainly is present before the onset of physical symptoms, the ultimate goal of researchers should be to find a way to diagnose the disease before it has progressed too far.

“[Here we] highlight the remarkable advances in our ability to detect evidence of Alzheimer’s disease in the brain, prior to clinical symptoms of the disease, and to predict those at greatest risk for cognitive decline,” explained lead author Reisa Sperling.

The common thread between these perspectives, say Neuron editors in an accompanying editorial, is that “by leveraging shared resources, tools and knowledge and approaching these difficult problems collaboratively, we can achieve more together.”

A sentiment that we at CIRM fully support—and one that we will continue to foster as we push forward with our mission to accelerate stem cell-based therapies to patients in need.

What everybody needs to know about CIRM: where has the money gone

It’s been almost ten years since the voters of California created the Stem Cell Agency when they overwhelmingly approved Proposition 71, providing us $3 billion to help fund stem cell research.

In the last ten years we have made great progress – we will have ten projects that we are funding in or approved to begin clinical trials by the end of this year, a really quite remarkable achievement – but clearly we still have a long way to go. However, it’s appropriate as we approach our tenth anniversary to take a look at how we have spent the money, and how much we have left.

Of the $3 billion Prop 71 generates around $2.75 billion was set aside to be awarded to research, build laboratories etc. The rest was earmarked for things such as staff and administration to help oversee the funding and awards.

Of the research pool here’s how the numbers break down so far:

  • $1.9B awarded
  • $1.4B spent
  • $873M not awarded

So what’s the difference between awarded and spent? Well, unlike some funding agencies when we make an award we don’t hand the researcher all the cash at once and say “let us know what you find.” Instead we set a series of targets or milestones that they have to reach and they only get the next installment of the award as they meet each milestone. The idea is to fund research that is on track to meet its goals. If it stops meetings its goals, we stop funding it.

Right now our Board has awarded $1.9B to different institutions, companies and researchers but only $1.4B of that has gone out. And of the remainder we estimate that we will get around $100M back either from cost savings as the projects progress or from programs that are cancelled because they failed to meet their goals.

So we have approximately $1B for our Board to award to new research, which means at our current rate of spending we’ll have enough money to be able to continue funding new projects until around 2020. Because these are multi-year projects we will continue funding them till around 2023 when those projects end and, theoretically at least, we run out of money.

But we are already working hard to try and ensure that the well doesn’t run dry, and that we are able to develop other sources of funding so we can continue to support this work. Without us many of these projects are at risk of dying. Having worked so hard to get these projects to the point where they are ready to move out of the laboratory and into clinical trials in people we don’t want to see them fall by the wayside for lack of support.

Of the $1.9B we have awarded, that has gone to 668 awards spread out over five different categories:

CIRM spending Oct 2014

Increasingly our focus is on moving projects out of the lab and into people, and in those categories – called ‘translational’ and ‘clinical’ – we have awarded almost $630M in funding for more than 80 active programs.

Untitled

Under our new CIRM 2.0 plan we hope to speed up the number of projects moving into clinical trials. You can read more about how we plan on doing there in this blog.

It took Jonas Salk almost 15 years to develop a vaccine for polio but those years of hard work ended up saving millions of lives. We are working hard to try and achieve similar results on dozens of different fronts, with dozens of different diseases. That’s why, in the words of our President & CEO Randy Mills, we come to work every day as if lives depend on us, because lives depend on us.