Stem cell stories that caught our eye: sickle cell patient data, vaccine link to leukemia protection, faster cell analysis

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Good news from sickle cell clinical trial. It is always satisfying to report positive results from human clinical trials using stem cells even when we don’t fund the work. Bluebird Bio released the first data on a patient treated for sickle cell anemia using the same procedure the company had earlier used to get good outcomes for two patients with beta thalassemia.

Both diseases result from defects—though different defects—in the gene for hemoglobin, the protein our red blood cells use to carry needed oxygen. So, in both cases they use a modified, deactivated virus to carry a correct version of the gene into patients’ own blood-forming stem cells in the lab. They then re-infused those cells into the patients to provide a ready supply of cells able to make the needed protein.

In the sickle cell patient, after the transplant a third of his red cells were making the right protein and that was enough to wean him off blood transfusions that had been keeping him alive and prevented any further hospitalizations due to the disease. The company also announced that the two previously reported patients treated for beta thalassemia had continued to improve. Reuters ran a story on the new data.

CIRM funds a similar project about to begin treating patients for sickle cell disease (link to video), also using a viral vector but a somewhat different one, so it is reassuring to see viral gene carriers working without side effects.

Another reason to vaccinate, prevent leukemia. While it has been known for some time that infant vaccination seems to have driven down the rate of childhood leukemia, no one has known why. A CIRM-funded team at the University of California, San Francisco, thinks they have figured it out. Viral infections trigger inflammation and the production of enzymes in cells that cause genetic mutations that lead to the cancer.

They worked with Haemophilus influenza Type b (Hib) vaccine but suggest a similar mechanism probably applies to other viral infections, and correspondingly, protection from other vaccines. The senior author on the paper, Marcus Muschen, explained the process in a university press release posted at Press-News.org

“These experiments help explain why the incidence of leukemia has been dramatically reduced since the advent of regular vaccinations during infancy. Hib and other childhood infections can cause recurrent and vehement immune responses, which we have found could lead to leukemia, but infants that have received vaccines are largely protected and acquire long-term immunity through very mild immune reactions.”

Barcoding individual cells. Our skin cells all pretty much look the same, but in the palm of your hand there are actually several different types of cells, even a tiny scratch of the fingernail. As scientist work to better understand how cells function, and in particular how stem cells mature, they increasingly need to know precisely what genes are turned on in individual cells.

Both techniques use tiny channels to isolate individual cells and introduce beads with "bar codes."

Both techniques use tiny channels to isolate individual cells and introduce beads with “bar codes.”

Until recently, all this type of analysis blended up a bunch of cells and asked what is in the collective soup. And this did not get the fine-tuned answers today’s scientists are seeking. Numerous teams over the past couple years have reported on tools to get down to single-cell gene analysis. Now, two teams at Harvard have independently developed ways to make this easier. They both use a type of DNA barcode on tiny beads that gets incorporated into individual cells before analysis.

Allan Klein, part of one team based at the Harvard Medical School’s main campus, described why the work is needed in a detailed narrative story released by the school:

“Does a population of cells that we initially think is uniform actually have some substructure. What is the nature of an early developing stem cell? . . . How is [a cell’s] fate determined? “

Even Macosko who worked with the other team centered at the Broad Institute of Harvard and MIT, noted the considerable increase in ease and decrease in cost with the new methods compared to some of the early methods of single cell gene analysis:

“If you’re a biologist with an interesting question in mind, this approach could shine a light on the problem without bankrupting you. It finally makes gene expression profiling on a cell-by-cell level tractable and accessible. I think it’s something biologists in a lot of fields will want to use.”

The narrative provides a good example of what we called the “bump rate” when I was at Harvard Med. Good science often moves forward when scientists bump into each other, and with Harvard Medical faculty scattered at 17 affiliated hospitals and research institutes scattered across Boston and Cambridge we were always looking for ways to increase the bump rate with conferences and cross department events. Macosko and Klein found out they were both working on similar systems at a conference.

Two for 2.0 and Two for us

It began as an ambitious idea; yesterday it became a reality when the CIRM Board approved two projects under CIRM 2.0, one of them a Phase 3 clinical trial for a deadly form of skin cancer.

Just to recap, CIRM 2.0 was introduced by Dr. C. Randal Mills when he took over as President and CEO of the stem cell agency last year. The idea is to speed up the way we work, to get money to the most promising therapies and the best science as quickly as possible. It puts added emphasis on speed, patients and partnerships.

Yesterday our Board approved the first two projects to come before them under this new way of working. One was for almost $18 million for NeoStem, which is planning a Phase 3 clinical trial for metastatic melanoma, a disease that last year alone claimed more than 10,000 lives in the U.S.

This will be the first Phase 3 trial we have funded so clearly it’s quite a milestone for us and for NeoStem. If it proves effective in this trial it could well be approved by the Food and Drug Administration (FDA) for use in melanoma patients. The therapy itself is unique in that it uses the patient’s own tumor cells to create a personalized therapy, one that is designed to engage the patient’s immune system and destroy the cancer.

The Board also approved almost $5 million for Cedars-Sinai in Los Angeles to do the late-stage research needed to apply to the FDA for approval for a clinical trial to treat retinitis pigmentosa (RP). RP is a nasty, degenerative condition that slowly destroys a patient’s vision. There is no cure and no effective therapy.

We are currently funding another clinical trial in this area. The two projects use different types of cells and propose different methods of reducing RP’s devastation. CIRM has a record of trying multiple routes to achieve success when dealing with unmet medical needs.

As Dr. Mills said in a news release, both the therapies approved for funding yesterday support our mission:

“CIRM 2.0 is designed to accelerate the development of treatments for people with unmet medical needs, and these two projects clearly fit that description. With the Board’s approval today we will now get this work up and running within the next 45 days. But that’s just the start. We are not just providing financial support, we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful. That’s the promise of CIRM 2.0. Faster funding, better programs and a more comprehensive approach to supporting their progress.”

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

Two seemed to be the number of the day yesterday with the Board welcoming two new members.

Dr. Adriana Padilla is the new Patient Advocate Board member for type 2 Diabetes. She’s a family physician, a member of the University of California, San Francisco-Fresno medical faculty, and an award-winning researcher with expertise in diabetes and its impact on Latino families and the health system in California’s Central Valley. She is also active in the National Hispanic Medical Association (NHMA) and is also a member of the American Diabetes Association.

Dr. Padilla said she hopes her presence will help increase awareness among Latinos of the importance of the work the agency is doing:

“When I was asked about being on the Board I did some research to find out more and it was really touching to learn about some of the exciting work that has been done by the agency and the possibilities that can be done for patients, including those I serve, members of the Latino community.”

Dr. Bob Price is the Associate Vice Chancellor for Research and a Professor of Political Science at U.C. Berkeley. His academic and teaching interests include comparative politics, with a particular interest in the politics of South Africa. This is Dr. Price’s second time on the Board.  He previously served as the alternate to UC Berkeley Chancellor Robert Birgeneau.

Although he has only been off the Board for a little more than a year Dr. Price said he is aware of the big changes that have taken place in that time and is looking forward to being a part of the new CIRM 2.0.

Stem cells, Darth Vader and the high cost of hope and hype

Darth Vader: Photo by Stefano Buttafoco

Darth Vader: Photo by Stefano Buttafoco

It’s not very often that you get stories about stem cells that mention Darth Vader, Obi Wan Kenobi, the Pittsburgh Steelers and a Beverly Hills plastic surgeon, but those references all popped up in a recent flurry of articles that are shining – yet again – the light on many of the unproven, unregulated uses of stem cells to treat everything from arthritis to Parkinson’s disease.

Let’s start with an article by Associated Press (AP) writer Will Graves who digs into the use of stem cells in sports.  Graves does a good job of highlighting all the reasons why an athlete would try a stem cell therapy quoting Dr. Jim Bradley, a team physician with the Steelers:

“They want the cutting edge, anything that is cutting edge that can get their guys a couple more years in the league. If I was an agent, I’d want the same thing.”

But Graves also does a fine job of pointing out that these therapies are unproven, and that in many cases athletes go overseas to get them because those clinics do not have to meet the same strict regulations as clinics here in the US.

“Traveling to a place like the Caymans, that’s like saying ‘I’m going to Mexico to have an appendectomy to save $80,'” said Dr. Matthew Matava, head physician for the St. Louis Rams and the NHL’s St. Louis Blues. “It looks like it’s not very smart or you’re grasping at straws.”

He also quotes Dr. Freddie Fu, head physician for the University of Pittsburgh athletics program, saying there is far too much uncertainty to take risks. Fu says in many cases the people delivering the therapies don’t even know where these stem cells might go, or what they might do:

“You can have one cell be Obi Wan Kenobi, the other is Darth Vader. You’re not sure which way it’s going to go.”

Matthew Perrone starts his piece in the Huffington Post, with a paragraph that is both gripping and disgusting:

“The liquid is dark red, a mixture of fat and blood, and Dr. Mark Berman pumps it out of the patient’s backside. He treats it with a chemical, runs it through a processor — and injects it into the woman’s aching knees and elbows.”

Berman, the co-founder of the largest chain of stem cell clinics in the US, admits he doesn’t know what’s in the mixture he is injecting into patients. But he says it can help treat more than 30 different diseases and conditions from Lou Gehrig’s disease to lupus and even erectile dysfunction.

Perrone’s piece is a long, detailed and thoughtful look at the finances that drive this business and how many stem cell clinics charge as much as $9,000 for unproven therapies. He quotes UC Davis stem cell researcher – and CIRM grantee – Dr. Paul Knoepfler:

“It’s sort of this 21st century cutting-edge technology. But the way it’s being implemented at these clinics and how it’s regulated is more like the 19th century. It’s a Wild West.”

But the price tag at those US-based clinics is tiny compared to how much some people are paying at overseas facilities. Los Angeles Times reporter Alan Zarembo focuses on the case of William Rader and his company Stem Cell of America.

Rader, a psychiatrist, had his medical license revoked by the Medical Board of California citing negligence, false or misleading advertising and professional misconduct. The Board said: “His dishonesty permeates every aspect of his business and practices.”

Yet Rader continues to charge up to $30,000 for stem cell procedures at the clinic he runs in Mexico. He uses the same procedure for different conditions, offers no scientific evidence it works but claims he’s helped many people and even cured a patient of HIV/AIDS.

For patients battling life-threatening diseases and disorders it is easy to see why they would be willing to take a chance on a therapy, any therapy, that might save their life.

And that’s where the danger in all this lies. What might be seen by an athlete as something worth trying to see if it might help extend their career a year or two, for people at the other end of life this may be their last chance, and that vulnerability means they’ll pay whatever they have to, for something that may be of no benefit whatsoever.

Telling an athlete this might help them play longer is one thing. Playing on a patient’s life or death fears is entirely another.

For more information on how you can make an informed decision about whether a stem cell therapy is right for you, particularly one offered overseas, go to our page on stem cell tourism.

Seth and Lauren Rogen Aim to Finish Alzheimer’s Film and End Lost Memories

When it comes right down to it, the closeness and love we feel for friends and family is based on our memories of shared experiences. But for Ken Dodson, those memories are evaporating:

It didn’t seem to progress as fast ‘til this year. This year I’ve noticed a lot more. I mean [my doctor] has already told me that it will be at the point where I don’t recognize any of my kids. That’s the hardest. There are some things you should never forget. I know one day I might.

Only 35 years old, Ken is stricken with early-onset Alzheimer’s. His tragic story is featured in, “This is Alzheimer’s”, a documentary being produced by film actor/writer/producer couple Seth Rogen and Lauren Miller Rogen. To help raise the funds needed to complete the project, the Rogens launched an online donation campaign, which ends tomorrow. You can view a clip of the documentary on their campaign page and below:

This film project is just one activity of the Rogens’ Hilarity for Charity (HFC) movement, which aims to raise awareness about Alzheimer’s among young adults and to fund research that could one day end this cruel disease. As mentioned on the HFC website, their efforts have been a hit so far:

For three years, our successful Los Angeles HFC Variety Show and our college program HFC U have entertained young, hip professionals through music and comedy while creating the next generation of Alzheimer’s advocates – not to mention raising over $2.5 million!

The Rogens’ innovative and inspiring charity work for Alzheimer’s hits close to home for a couple of reasons. For starters, our agency has awarded over $52 million to stem cell related Alzheimer’s research which aims to better understand the disease and to work towards bringing stem cell-based treatments to clinical trials. And Lauren Miller Rogen is not only a co-founder of Hilarity for Charity but also serves as the Alzheimer’s patient advocate on the CIRM governing Board. Alzheimer’s has personally affected Lauren’s family: Lauren lost her grandfather and grandmother to the disease and, like Ken Dodson, her mother Adele was diagnosed with early-onset Alzheimer’s at just 55 years of age. Before she reached 60, Adele couldn’t write, speak, or recognize her family.

When it comes to developing therapies for unmet medical needs, it’s crucial to approach diseases from many angles in order to identify the best approaches more efficiently. The same holds true for raising awareness and funding research. That’s why the Rogen’s documentary is an important piece to the puzzle of ending Alzheimer’s and lost memories.

Taking a step back, to move forward

Progress doesn’t always come in straight lines. Particularly when you are a pioneer in a whole new field of medicine like stem cells where virtually everything you do is being done for the first time, and the therapies you are developing are going to be tested in people for the first time. That’s why everything you do has to be done with extra caution to make sure the best interests of the patients come first. Sometimes that means not rushing ahead, but pausing, while you decide what is the best approach.

SangamoThat’s what Sangamo have done in announcing they are delaying the start of their clinical trial in beta thalassemia – a trial we are funding.

They are taking what amounts to a “time-out” so that they can make a small change in direction, one they – and we – hope will ultimately prove most effective for patients.

Βeta thalassemia is a genetic disease that results in patients producing red blood cells with poorly functioning hemoglobin, the protein that carries oxygen to all our tissues. If not properly managed the condition can be fatal.

The approach Sangamo are taking to cure the problem involves using zinc finger nuclease (ZFN), a kind of molecular scissors, to genetically edit the patient’s own stem cells, correcting the problem and enabling them to produce healthy hemoglobin and healthy red blood cells.

But as they geared up for the clinical trial, one that was approved by the Food and Drug Administration (FDA), they did some preclinical testing and saw that an approach they were using on a similar disease – sickle cell disease (SCD) – appeared to be more efficient and effective at correcting the underlying genetic problem. Both used ZFN to edit the defective gene, but they both had slightly different targets on those genes. The one targeting SCD seemed to have some key advantages, so they have decided to switch to this approach for both conditions.

In a news release Edward Lanphier, Sangamo’s President and CEO, says it wasn’t an easy decision to make, but it is the right decision:

“While our joint decision will result in a delay in the initiation of the beta-thalassemia Phase 1 clinical trial, we believe that the efficiency of the consolidated development path and potential benefit to patients clearly support this decision.”

The next step is for Sangamo to go back to the FDA and file a new Investigational New Drug or IND application for this new approach to beta-thalassemia. They’re hopeful they’ll be able to get that approval, and move ahead with their clinical trial next year.

The good news is that thanks to our new way of funding under CIRM 2.0, Sangamo will have the opportunity to seek CIRM’s support for its work through both our preclinical program, as they make their changes, and then our clinical program if and when they get FDA approval to move ahead. This uninterrupted support is what CIRM 2.0 was set up to achieve, to move promising projects like this to patients as quickly as possible.

For the team at Sangamo it’s obviously disappointing to have to stop and change direction. It’s also disappointing for the patients hoping this would lead to a more effective therapy, even a cure.

But this is not a set back. Rather, it’s a step back. One that allows Sangamo to choose what they believe is a better option, one that will ultimately be much better for patients.

Stem cell stories that caught our eye: reversing aging, mature hearts, arthritic knees and tiny organs

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Making stem cells feels young again. Stem cells are supposed to rejuvenate our tissues, whether brain or muscle, and keep them functioning at their peak. But the aging process seems to poison the environment where stem cells reside and prevent them from getting the job done.

A CIRM-funded team at the University of California, Berkeley, has found a drug that can reverse the effect of aging and make the stem cells function better and in turn make tissues behave like younger versions of brain or muscle. Their previous work had shown that old tissues had much more of one growth factor, TGF-beta1, than young tissue. When the team, led by David Schaffer and Irina Conboy, blocked the activity of that growth factor with a cancer drug already in clinical trials they saw rejuvenated youthful tissue—in mice.

HealthCanal picked up the university’s press release, in which Schaffer described the broad effect of the treatment:

“We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle. That is good news, because if every tissue had a different molecular mechanism for aging, we wouldn’t be able to have a single intervention that rescues the function of multiple tissues.”

The team, however, noted that multiple molecular signals are in play in the aging stem cell’s environment and optimum intervention may require using more than one drug and getting the dosages just right. Conboy said that the task was to “recalibrate the environment to be youth-like.”

Maturing of the heart. Scientists can turn embryonic stem cells into most forms of adult tissue, but often those tissues don’t function like fully mature forms of the organ they are supposed to be. Now a consortium of researchers has identified a molecular switch that seems to be able to take stem cells and get them to form fully mature heart muscle.

In an interview with Genetic Engineering & Biotechnology News, senior author on the paper Hannele Ruohola-Baker of the University of Washington noted the breakthrough:

“Although we can now induce embryonic stem cells to become heart cells, getting them to mature to an adult-like state remains a significant challenge. We believe we’ve now found the master switch that drives the maturation process.”

The researchers found the molecular switch by studying many of the genetic switches called micro-RNAs in both young and old heart muscle cells. The one linked to helping stem cells mature interestingly is also involved in up-regulating metabolism and it makes sense that a supercharged metabolism would be valuable for fully functional heart muscle.

Some answers may be coming on stem cells and knees. While many clinics around the word offer to treat arthritic knees with stem cells taken from a patient’s own fat—often for large sums of money—very little data exist on the outcomes of those treatments. So, it was great to read this week that a European consortium is about to launch a large trial that should provide some quality data.

The ADIPOA-2 trial will enroll 150 patients in a randomized way so that the stem cell treatment can be compared to standard therapies, and the researchers will handle processing of the fat stem cells in a consistent way across clinics in four countries. It follows a phase 1 ADIPOA trial with 18 patients that showed promising results.

Frank Barry of the National University of Ireland Galway is coordinating the phase 2 trial and was quoted in the university’s press release picked up by HealthCanal:

“The results from ADIPOA’s first-in-man-trials were very encouraging and paved the way for another study to further test the safety and effectiveness on a wider scale. ADIPOA-2 is bringing together Europe’s leading scientific, clinical and technical expertise on this project.”

A lingering question remains about how long any benefit from the stem cell therapy will last. Some researchers have suggested that fat stem cells can only form soft cartilage like in your ear lobe and not the articular hard cartilage normally in your knee. So, it will take some years of follow-up to see if any new cartilage made by the stem cells can stand up to the beating of a good tennis match or hike up a mountain.

CIRM funds a research team at the University of Calirfornia, San Diego, that believe they have found a way to get embryonic stem cells, which are more versatile than fat stem cells, to form the hard articular cartilage.

Great hope in tiny little organs. For the past couple years one of the hottest areas of stem cell science has been growing stem cells in 3-D cultures in the lab and getting them to self organize into multi-tissue layers that mimic some function of one of our vital organs. It has been done for the eye, lung, liver, kidney and brain, but the first was the intestine, and the researcher behind the advance, Hans Clevers, dubbed them “organoids.”

The journal Nature just published a good Q&A interview with Clevers who works at the Hubrecht Institute Utrecht, the Netherlands. In it he describes how organoids will be a useful tool for drug screening and how his team is working on ways that organoids made from a patient’s own cells could be tested in the lab for sensitivity to specific cancer therapies.

How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

Dying cells signal their moms, aka stem cells, to protect themselves so that they can make replacements cells.

I love the name for stem cells in Spanish, células madre, or mother cell. It seems appropriate that the sons and daughters of our stem cells send a warning to mom to protect herself when they are under attack. Specifically, a team at the University of Washington reported Monday in Nature Communications, that when cells die from radiation or chemotherapy, they send a chemical signal that causes the nearby stem cells to flip a genetic switch that prevents them from dying.

This ability helps our bodies recover from cancer treatment, but it could also be one reason so many cancers return. While we want our normal stem cells to retain the ability to replace damaged tissue, that benefit may come with an unwanted corollary. The closely related cancer stem cells that can generate new tumors may have the same ability.

The researchers found that dying cells release a protein that binds to a receptor on the surface of stem cells. That in turn triggers the stem cells to produce a genetic tool that switches off a key gene that would normally tell the stem cells to die because of damage to their DNA caused by the therapy.

Having survived the programmed cell death normally triggered by DNA damage, the stem cells have time to repair their DNA and go on to reproduce healthy tissue. This pathway—the protein released by the dying cell to the genetic switch in the stem cell—could also become a target for cancer therapy. It could provide a way to prevent the cancer-initiating stem cell from surviving the chemotherapy or radiation.

A press release from the university quoted one of the researchers on the therapeutic potential:

“There are very similar genes and proteins in human cancers that are likely playing the same role of protecting the tumor-initiating cells from destruction. As a result, the tumor-initiating cells survive and the cancers return. By targeting these factors, perhaps by blocking [the stem cell surface] receptors, it may be possible to block the protective signal from the daughter cells, and thereby allow programmed cell death to proceed in the [cancer] stem cells and prevent cancer.”

Eat some veggies; kill some cancer stem cells

This past Sunday sons and daughters far and wide thanked their mothers for all the love and wisdom they provided. I hope they also thanked mom for nagging them to eat their veggies especially the cruciferous ones like broccoli, Brussels sprouts and cabbage. Based on research from South Dakota State University (SDSU), it turns out these foods contain a natural plant chemical that appears to kill cancer stem cells, the cells thought to be responsible for the reoccurrence and spread of certain cancer types.

South Dakota State University doctoral student Bijaya Upadhyaya and associate professor Moul Dey and others published a study suggesting a natural chemical found in plants could potently kill cancer stem cells.

South Dakota State University doctoral student Bijaya Upadhyaya and associate professor Moul Dey members of team that report plant chemical potently kills cancer stem cells. (Credit: South Dakota State University)

Like stem cells, cancer stem cells can make copies of themselves. But instead of growing into tissues and organs, cancer stem cells propagate the cancer and mature into the many cell types found in a tumor or leukemia. Standard treatments like chemotherapy and radiation target rapidly dividing cancer cells but the cancer stem cell can lie dormant and evade these treatments. Plus they only make up a small percentage of the cancer. So a seemingly successfully treated patient can relapse if any cancer stem cells remain and begin propagating the tumor once again. The SDSU team and others had previously shown that the plant chemical phenethyl isothiocyanate (PEITC) – formed by an enzymatic reaction during the chewing process – had anti-inflammatory and cancer cell killing properties. In research published last summer and reported just last week in a university press release, the researchers for the first time looked at the effects of PEITC on cancer stem cells. They isolated cancer stem cell-like cells from HeLa cells, a cervical cancer cell line (the cells made famous by The Immortal Life of Henrietta Lacks). In petri dish experiments they showed that PEITC had a potent effect on the cancer stem cells, killing 75% within 24 hours. Detailed analysis suggested that PEITC acted by increasing the level of proteins involved in programmed cell death, also called apoptosis.

150512_Fig-5Eiv-PEITC-preventing-metastasis-in-lungs

Plant compound, PEITC, prevented spread of cervical cancer cells into this lung tissue. (Credit: South Dakota State University)

To provide a proof of principle that this cancer cell killing activity of PEITC has the same effects in the body, the team studied tumor formation in mice after injection of the cancer stem cells with or without pretreatment with PEITC. Sure enough, the PEITC treated animals showed a 70% reduction in tumor formation compared to the untreated group. To study potential effects of PEITC on the spread of tumors to other parts of the body, the team analyzed lung tissue in the animals. Only untreated animals had tumors in the lung tissue suggesting that PEITC blocked tumor spreading. Certainly more testing is needed to confirm these results in humans but if every thing pans out, PEITC clinical trials could be on the horizon, either alone or in combination with cancer therapies that target programmed cell death. In the meantime, it can’t hurt to listen to mom and take a second helping of broccoli. CIRM funds a number of projects, including three clinical trials, that focus on cancer stem cells. For more information, please visit these web pages:

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network here.