A rare day for raising rare disease awareness

Most years there is no February 29, and most of the time it might feel like there is little or no help for people with rare diseases. That’s what makes leap day the perfect day to think about those roughly 7,000 diseases that each affect fewer than 200,000 people in the U.S. at any time.

Despite the small number of people affected by any one rare disease, together they add up to about 30 million people in the U.S. who contend with diseases that are poorly understood, poorly funded and in many cases lack national support groups.

The Rare Disease Day website lists activities throughout the world where people can learn more about rare diseases and the path to new therapies. It also includes a page describing how people can take action to get more support and awareness for rare diseases.

CIRM has several research programs focusing on rare diseases, including an $11 million award to Stanford researchers who are working toward a therapy for the lethal childhood skin condition epidermolysis bullosa. They are hoping to file with the food and drug administration to begin clinical trials in the next few years. You can watch videos of these researchers talking about the disease and their therapy approach here.

Other rare disease research projects that are within a few years of clinical trials include a $9 million award for a sickle cell disease therapy, two projects worth $34 million for HIV/AIDS (video about that project here), a $10 million award for ALS (Lou Gehrig’s disease) (video about that project here), and a $15 million award for macular degeneration (video about that project here). In addition, several of our cancer projects could benefit the many rare forms of cancer that affect only a small number of people.

CIRM also funds research at various stages of progress toward developing therapies for spinal muscular atrophy, multiple sclerosis, muscular dystrophy, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, Autism, retinitis pigmentosa and Rett Syndrome, all of which are considered rare diseases in the U.S..

You can see a complete list of rare disorders on the National Organization for Rare Disorders (NORD) web site. In Europe, Eurordis also has an excellent web site about rare disorders and YouTube channel featuring patient stories.

Prior to 1983, rare disorders were at a therapeutic disadvantage in the U.S. because pharmaceutical companies couldn’t make a profit developing drugs to treat diseases with small patient populations. As a result of a national effort on the part of patient advocacy groups, the Orphan Drug Act passed, giving special status to drugs that would treat rare diseases.

Tim Cote, chief medical officer of NORD, spoke at a rare disease caucus (you can watch his entire talk here). During his talk he said:

“The orphan drug act is, bar none, the single piece of legislation that is the most successful in the history of the United States of America. Orphan drugs have become the biggest growing part of the pharmaceutical sector.”

He went on to say that the Orphan Drug Act wasn’t intended to let bad drugs through the system, but to inspire companies to develop and test transformative new therapies.

“People with rare diseases are entitled to drugs that actually work. The policy of our day is how to stimulate innovation and build upon these successes while retaining efficacy standards that have served us so very well to date and deliver science from the laboratory to the bedside without delay.”

We recently produced a video with Victoria Jackson, whose daughter was diagnosed with the rare disorder neuromyolitis optica. She tells an inspiring story about founding a disease organization and prodding the small research community to start working more effectively—and quickly—toward a therapy for her daughter and other people with the disease.

Jackson’s is a compelling story about the power of patient advocates to make a real difference in accelerating the development of therapies—a story that is not unlike the passage of the Orphan Drug Act and CIRM’s own origins with the passage of proposition 71.


Ellen Feigal discusses CIRM’s Huntington’s Disease research

Yesterday Ellen Feigal, CIRM’s Senior VP of R&D spoke on The HD View with Melissa Biliardi, who is a caregiver and advocate for her son who has Juvenile Huntington’s Disease. You can listen to that hour interview here.

Feigal started by talking about what is unique about CIRM, saying:

It’s the transformative nature of CIRM’s mission which is really to help patients who have debilitating diseases and injuries and it’s doing it in a very special way. That’s by trying to advance very innovative stem cell science into potential therapies and cures. There’s still a lot of urgent unmet medical needs.

CIRM came about through Proposition 71, which was driven primarily by patient advocacy groups who were eager for new stem cell-based therapies. Feigal talked about that patient focus in the research CIRM funds:

We fund basic ideas but it’s applied toward the human diseases or injuries. There’s a connection with the medical need. The basic type of research is the fundamental engine of discovery, which is essential and will continue, but what we are increasingly looking at are those types of programs that are necessary to get a product into people.

So far, CIRM has 43 translational awards in 26 disease areas that are in various stages of working towards clinical trials. You can read more about those programs on our web site. You can also read about our projects focusing on Huntington’s disease.

In answer to a question about what patient advocates can do help promote research toward a cure Feigal said:

We need to keep that engine of discovery alive. We need patient advocacy organizations to keep the urgency up there. We need researchers interested in focusing on this area. There’s a lot we still need to understand. It takes patient organizations and it takes funding to move these programs forward.

The program closed with information about how people can keep up-to-date on CIRM activities. In addition to following this blog, people can sign up on our web site to receive CIRM’s monthly newsletter and our press releases. Melissa Biliardi also noted CIRM YouTube channel CIRMTV where we post videos about CIRM initiatives and progress toward disease therapies. Here’s a video we produced about research toward a therapy for Huntington’s disease.


CIRM grantees married to their work, spinal cord injury cure

On Valentine’s Day, Pat Brennan of the Orange County Register visited the home of CIRM grantees Brian Cummings and Aileen Anderson in Irvine. In addition to sharing a life, the couple also shares a research effort to develop a stem cell-based therapy for spinal cord injury. Their combined work has been funded in part with $3.6 million from CIRM (here are links to a SEED award and Early Translational II award to Cummings and a Basic Biology II award to Anderson).

Brennan walked with them to work, after tagging along on a dog walk and a trip to drop their 6-year-old daughter at school.

Later, the conversation transitions into a science meeting as the two take the 20-minute walk past UCI’s Ecological Preserve and into the Sue and Bill Gross Stem Cell Research Center. The energy-efficient building, with an open design to encourage chance meetings among scientists, houses a roster of high-powered researchers as well as their experimental subjects: rodents.

The center was seeded by $27 million in state stem-cell funding and $10 million from donors Bill and Sue Gross. The building was completed in 2010.

Now, researchers working there cultivate lines of human embryonic stem cells that can grow into a variety of cell types, from brain cells to liver and heart cells.

A trial based on work by the couple, in collaboration with StemCells, Inc is underway in Switzerland (we blogged about that trial here).

The $27 million in state stem cell funds was a Major Facilities grant from CIRM. The story goes on to discuss the origins of CIRM and misconceptions about stem cells:

Created by voter initiative – Proposition 71 in 2004 – CIRM is California’s $3 billion answer to federal restrictions on funding for stem-cell research. Those restrictions were started by the Bush administration and eased, but not eliminated, under President Obama.

Cummings said opposition to their research is based, in part, on incorrect assumptions.

A big one is that the research involves the destruction of embryos. In reality, they work with balls of cells created at an earlier stage of human development, called blastocysts – a distinction many opponents do not draw.

“Embryonic stem cells don’t come from embryos,” he said. “And they never have.”

The raw material comes from fertility clinics and otherwise would be discarded.

Cummings says those who say that such research is immoral have it wrong.

“The argument is backward,” he said. “It’s immoral to throw away this stuff and not use it to help someone.”

You can learn more about CIRM awards targeting spinal cord injuries and videos about the work on our web site.


Stem cells can screen drugs for sometimes-lethal side effects

CIRM grantee Bruce Conklin recently spoke at the California Academy of Sciences about using reprogrammed skin cells (so-called iPS cells) to test drugs for lethal side effects in the heart. You can see a 4 minute excerpt of that talk here. One of the most common reasons for a drug to fail clinical trials is that it causes a heart rhythm defect called long QT syndrome. He argues that it could save money in clinical trials—and save lives—if stem cells could be used to screen the drugs to eliminate those that cause long QT syndrome before they are tested in people. There is currently no effective way of testing drugs for heart-related side effects before the drug enters clinical trials.

Conkin, who is a Senior Investigator at the Gladstone Institutes in San Francisco, has a CIRM New Cell Lines grant to develop iPS cells and mature them into heart cells. The idea would be to then put drugs in the dish with those beating heart cells and screen the cells for signs of long QT syndrome.

In the talk Conklin said:

What if you had just been prescribed a new medication and you’d gone to Walgreens and picked it up and taken the medication and then suddenly fainted and passed out. One possibility would be that you fainted because you’d had one of these [long QT] episodes and that you’d had a near-lethal arhythmia. One possibility to determine whether that drug caused the arhythmia would be of course to take the drug again and see whether or not it reoccurred. Now, although I’m sure you are supportive of medical research this is probably not advisable.

However, now one could have a different alternative. Perhaps we could recommend that we take a skin biopsy, we take that skin biopsy and grow iPS cells. WE grow heart cells from those iPS cells and we test the drug on those cells. That indeed would be something that you could potentially take part of and be supportive of.

We also produced a video of Conklin discussing this work.


Jonathan Thomas discusses plans to extend CIRM’s benefits to California

Jonathan Thomas is chair of the CIRM governing board.

This week CIRM delivered a document to the governor, state controller, state treasurer and state legislature describing how CIRM intends to ensure that its mission extends beyond the $3 billion authorized by proposition 71. Based on our current estimate, we expect to issue the final grants five years from now in 2017. The organization will maintain a staff to oversee those multi-year awards through 2021.

Remember that five years ago, Shinya Yamanaka had just made his discovery that skin cells could be reprogrammed to embryonic-like iPS cells—a technology that now makes up roughly 20 percent of our research funding. We have no way of predicting what technologies that don’t yet exist will bring the next revolution in stem cell science, and we certainly can’t know what advance will bring new therapies, lower health care expenses, create jobs and leverage investment to California.

Given those uncertainties, the plan we delivered is a set of ideas that we’ll be pursuing over the next decade to ensure that the vision of California voters extends beyond the life of the agency.

The first $1.1 billion in awards, by 2014 will have leveraged $860 million in additional investment to California, created 25,000 job years, and brought in 200 million in tax revenue for the state, all while capping administrative expenses at less than six percent. The transition plan we provided describes mechanisms for continuing and expanding those benefits to the state of California.

Throughout the next decade, CIRM intends to ensure that grantees have the tools they need to turn basic discoveries into cures. We will protect our IP to safeguard the state’s investment and will make sure that authority for monitoring CIRM loans is transferred appropriately. We will also continue to encourage the growth of California’s biotechnology industry to sustain CIRM’s mission into the future.

Moving forward, we are pursuing opportunities to collaborate with disease foundations, which have already made significant contributions to CIRM’s programs. We will continue to promote our efforts to allow California researchers access to intramural resources at the National Institutes of Health, and we will explore the possibility of an independent venture philanthropy program to fund phase 1 and phase 2 research programs in stem cells and regenerative medicine. If and when we can make a compelling case based on the total performance of CIRM-funded projects, we will also consider whether or not to pursue additional public funding for CIRM itself. All of these efforts will be carried out so that stem cell programs started under CIRM are able to reach patients in California and around the world.

As Alan Trounson, president of CIRM, and I say in our plan:

Our lasting accomplishments will include physical infrastructure to house thousands of stem cell researchers in California; the recruitment and training of over one thousand new scientists within the state; a pipeline of translational and clinical development programs; international relationships advancing and accelerating stem cell research throughout the world; and numerous biotechnology companies focused on stem cell research within California. Collectively, this legacy will allow California to continue world leadership in the coming decades.

Here is a copy of the transition plan posted on the CIRM website [pdf].

Francis collins on stem cells, disease modeling, and finding therapies

Former CIRM board member John Reed, Professor and CEO of Sanford-Burnham Medical Research Institute, recently interviewed Francis Collins for Medscape one-on-one. Collins is Director of the National Institutes of Health (NIH), and a vocal supporter of funding stem cell research.

The interview covers Collins’ own beginnings in science and advances over the last decade in genome sequencing as well as the role of the internet in the doctor-patient relationship. It’s a fascinating conversation and well worth listening (the full text of the conversation is also available).

Collins also discusses the importance of modeling diseases using stem cells reprogrammed from adult cells, something we’ve blogged about frequently. Collins says:

If you’re studying Parkinson disease, for instance, and you want to know what’s really going on in the neurons, you probably don’t want to do that by performing brain biopsies in people with Parkinson disease, but you could take a skin biopsy, convert those cells to IPS cells, and then add the appropriate cocktail, and differentiate those into dopamine-producing neurons; then, you have a pretty good model of what’s going on in the brain. You could then use those neurons, and people like you are doing this, to be able to assess among a library of possible drugs what would be the one that would be most likely to make those neurons happy. That is now being done for dozens of diseases, using this as a model of doing drug screens without having to depend on animal models (which sometimes have misled us), without having to just hope for the best and expose patients to drugs with less evidence. This is profound, with lots of potential there.

Collins goes on to talk about using stem cells—adult, iPS or embryonic—to directly treat disease:

At NIH, we have just started a new center for regenerative medicine on the campus, which has the use of our clinical center with its 240 research beds as a real possibility of pursuing cell therapy using stem cells. I don’t know for which diseases this is going to work, but I bet it’s going to work for some, and I bet it will be pretty transformative in the array of opportunity we have to treat diseases that are pretty frustrating right now.

Collins also made a point about the importance of basic research in the development of new therapies. CIRM has put significant funds into the later stages of research attempting to bring new therapies to clinical trials. But we also fund the basic research that is the engine for new discoveries and new ideas for how to treat disease. Collins says:

The work done by Elizabeth Blackburn and Carol Greider on telomeres, for which they won the Nobel Prize. Something that seemed so abstract, something that they studied in slime mold, of all places, and which now is profoundly important in our understanding of cancer and of aging, is just breathtaking as an example of a molecular insight into conditions that we never dreamed would have that particular connection.


CIRM: the audacious vision is still possible

This weekend the Sacramento Bee ran an opinion piece about the future of stem cell research in general, and CIRM’s role in particular. The story was interesting in its focus on the process of developing and funding a new therapy—which can be long and arduous, and it only getting more so.

David Lesher wrote:

Those who speculate say that the most advanced stem cell treatments are still probably a decade away from becoming available to patients. And the cost to get them there will far exceed California’s $3 billion investment. The hope was that California’s bond would jump-start a biotech industry by building the laboratories and seeding early research to a point where private support would take over.

But that point of commercial viability is a moving target as private investors have grown more risk averse and the regulatory path for such radical new therapies is unpredictable. So the biggest question today in the stem cell field is not whether the science will work someday. The big questions are how will we pay for it, how will regulators know when it’s ready and when will it happen?

“We are at a time when venture capital doesn’t invest as early as it used to,” said Larry Goldstein, a leading stem cell scientist at UC San Diego. “So the public has to do it. You may not like the system, but that’s the system.”

CIRM is all too aware of the difficulty of getting industry and investors to pick up promising new therapies. We’ve ramped up our efforts this year to engage with those groups and introduce them to the CIRM-funded projects that are in the pipeline (you can read our blog about those efforts). The hope is by getting researchers interacting with potential industry partners early on, those projects will be attractive to investors who can support them through clinical trials.

The story went on to talk about CIRM’s 43 projects in 26 disease areas that are currently in the pipeline toward clinical trials. You can read more about that portfolio on our web site. The Sacramento Bee quoted CIRM board member Sherry Lansing talking about the portfolio:

“This is what the taxpayers are waiting to see,” Sherry Lansing, a member of the board, said after the presentation. “You keep reading these articles – ‘Where are the results? Where is the beef?’ Now I think we can really answer that.”

Lesher makes clear that there are many challenges ahead in bringing new therapies to patients: he said of the voters who created CIRM, “It was pretty audacious of them in 2004 to try to create another economic driver like Silicon Valley and save lives at the same time.”

And while the vote was audacious, we agree with his conclusion that despite risks and challenges that vision is still possible.


Valentine’s Day Stem Cell Wish: Mending Broken Hearts

At CIRM, our Valentine’s Day present came in the form of a paper published in The Lancet by grantee Eduardo Marban. He showed the results of a study finding that stem cells taken from the heart can help reduce scar tissue after a heart attack.

Marban, who is director of the Cedars-Sinai Heart Institute, spoke to our governing board earlier this year about the study, which forms the basis of a $5 million CIRM disease team award. You can read more about Marban’s research and see a video of his talk by visiting our earlier blog about the work.

CBS news had this to say about Marban’s results:

For the study, researchers tested 25 patients, an average of 53 years old, who had experienced heart attacks that had left them with damaged heart muscle. Eight patients served as controls and were treated with conventional treatments including medication, and diet and exercise recommendations. The other 17 patients received stem cells, which researchers derived from raisin-sized pieces of patients’ own heart tissue.

The researchers found that patients treated with stem cells experienced almost a 50 percent reduction of heart attack scars within 12 months of treatment, while the eight patients who received conventional treatment saw no reductions in damage.

We hope one day research such as this (and others funded by CIRM) will be mending broken hearts.


Personalized medicine may help treat childhood brain tumors

Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.

When CIRM grantee Robert Wechsler-Reya received a Leadership Award to lure him from Duke University to the Sanford-Burnham Medical Research Institute in La Jolla, California, it was with the idea that his cancer stem cell research would point to new therapies for forms of cancer. Less than a year after moving to the state, it’s doing just that.

Wechsler-Reya and an international team of researchers have just published work describing a group of proteins that seem to drive a particularly aggressive form of the childhood brain tumor called medulloblastoma. Kids with this form of cancer have a high survival rate, but the treatment itself can leave them with a significant risk of other disorders and with mental impairments.

Wechsler-Reya’s work could help in developing drugs that effectively treat the cancer and have fewer side effects, so the kids can go on to lead a more normal life after treatment.

The work, published in the journal Cancer Cell, is dedicated to a little boy named Cameron Jackson who died earlier this year after a long battle with medulloblastoma.

Some, but not all, forms of medulloblastoma contain abnormally high levels of a gene known as Myc (pronounced “mick”). Working in mice, they discovered that these tumors are particularly dependent on a group of proteins involved in cell survival. When they exposed tumor-bearing mice to a drug that reduces the activity of those proteins, the mice lived longer.

As it happens, there are drugs that specifically target those proteins being tested in other forms of cancer. Wechsler-Reya is quoted in a press release from Sanford-Burnham:

“Obviously there are many steps between screening compounds in the lab and giving drugs to patients,” Wechsler-Reya said. “But some of the steps can be cut short if you use drugs that are already in trials or in use for other diseases.”

This work is an important step toward personalized medicine. Instead of treating all kids who have medulloblastoma with the same drug, a doctor might one day be able to screen the child’s tumor, find out which genes have gone awry, and specifically treat that tumor with the drugs that will be most effective.

You can read more on our website about CIRM grantees working toward therapies for forms of brain tumors.


Pei, Y., Moore, C., Wang, J., Tewari, A., Eroshkin, A., Cho, Y., Witt, H., Korshunov, A., Read, T., Sun, J., Schmitt, E., Miller, C., Buckley, A., McLendon, R., Westbrook, T., Northcott, P., Taylor, M., Pfister, S., Febbo, P., & Wechsler-Reya, R. (2012). An Animal Model of MYC-Driven Medulloblastoma Cancer Cell, 21 (2), 155-167 DOI: 10.1016/j.ccr.2011.12.021

CIRM grantee Sheng Ding among the Bay Area’s 40 leaders under 40

Sheng Ding of the J. David Gladstone Institutes in San Francisco has been making a name for himself in stem cell circles. Now he’s being recognized in the business community, earning a place on the San Francisco Business Times’ 2012 40 under 40 roster. Ding has a New Faculty Award and a New Cell Lines Award from CIRM.

He joins CEOs, founders and senior executives of such companies as Solar City, Yammer, and Stella & Dot, as well as a Tony winning producer and other leaders. In their story about the group, the San Francisco Business Times wrote:

For the first time, the Business Times is honoring standout leaders under 40 years old making a major impact on the Bay Area’s economy, community and culture by employing innovation, business and technical acumen and a lot of hard work. If, after learning more about these under-40 wizards, you start to feel badly about yourself, trust that you are not alone.

Ding earned his place in the line-up through his work directly converting one type of cell into another. This work, called direct transformation, has been receiving a lot of attention in the past two years because of the possibility of one day converting cells within the body to another cell type as a way of repairing damage.

We’ve blogged about Ding’s work converting skin cells into beating heart cells while he was at Scripps Research Institute and then later converting skin to neural stem cells. Both of these experiments were in mice, and so are not yet primed for human therapies. However, his work is part of a growing trend that includes some recent work carrying out similar cellular fate-changes using human cells.

The fact that this CIRM-funded work was recognized as driving the bay area’s economy is a nod to the importance of the biotechnology industry in the area, and to the importance of basic research such as Ding’s in fueling the growth of those companies.