Moving Beyond Current CIRM Funding

Delivering on CIRM’s mission of “accelerating stem cell treatments to patients with unmet medical needs” requires the participation of multiple stakeholders to span the research, development, and commercialization phases of bringing a new product to market. In this post, I am pleased to highlight two recent examples of CIRM-funded projects moving beyond their period of CIRM funding by establishing partnerships with industry and investors to further develop the underlying CIRM-funded technology.

In 2000, Dr. Jill Helms, an academic investigator at Stanford University, received a $6.5 million grant from CIRM under an Early Translational award. The title of Dr. Helms’ project was Enhancing Healing via Wnt-Protein Mediated Activation of Endogenous Stem Cells,” and the goal of the award was to develop a novel, protein-based therapeutic platform to accelerate and enhance tissue regeneration through activation of adult stem cells. The five-year award achieved many critical milestones along the way, including the initiation of two preclinical studies aimed at demonstrating the effectiveness of a protein called L-WNT3A to improve the success of spinal fusion surgery and to treat a degradative bone disease called osteonecrosis, both of which represent unmet medical needs.

Helms_bonegraft

Through CIRM funding, Dr. Jill Helms’ team was able to demonstrate that treatment with a protein called L-Wnt3a regenerates and promotes bone formation in animals models (Figs D,F: untreated; Figs E,G: Wnt3a treated). (image credit: Leucht et al. J Bone Joint Surg Am. 2013;95:1278-88)

Dr. Helms’ work attracted considerable interest from the investor community during the lifespan of her grant, and during the final year of her award Dr. Helms’ WNT3A technology platform was successfully spun out of Stanford into a newly created company called Ankasa Regenerative Therapeutics. Ankasa was established with the financial support of Avalon Ventures – a La Jolla based life sciences venture capital firm, Correlation Ventures – an analytics driven venture capital firm, and Heraeus Medical – a diversified global medical device company based in Germany with over $1 billion of annual revenue. Ankasa has raised an initial $8.5 million in the first round of the total $17 million Series A financing to continue the development of the previously CIRM-funded technology.

Moving Radially Branched Deployment_Neurosurgery_Lim

Dr. Daniel Lim’s CIRM-funded BranchPoint Device allows neurosurgeons to deliver cell based therapies to multiple areas of the brain with just one needle penetration.  (image credit: Silvestrini et al. Stereotact Funct Neurosurg 2013;91:92–103)

The second recent example comes from a CIRM Tools & Technology grant to Dr. Daniel Lim, a neurosurgeon at UCSF. Dr. Lim was awarded a $1.8 million grant to develop a more efficient device for transplanting stem cells into the brain, titled Development and Preclinical Testing of New Devices for Cell Transplantation to the Brain.” Dr. Lim successfully developed a platform technology that enables Radially Branched Deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. This technology is a huge leap forward over the conventional and crude syringe and needle device that are typically used to inject living cells into the brain.

Dr. Lim’s work attracted the attention of Accurexa, a publicly traded medical device company that licensed the CIRM-funded technology from UCSF. Under the guidance of Accurexa, a 510(k) application was submitted to the FDA for the newly coined “BranchPoint Device.” In June of this year, Accurexa successfully raised $2.5 million in equity financing to continue the development and for commercialization of the BranchPoint Device.

Overall, there remains a lack of industry pull for early stage stem cell technologies, however, both Drs. Helms and Lim’s stories represent successful examples of CIRM providing public dollars for early stage research with the resulting potentially life-saving applications attracting interest from investors and companies. These new investors will further fund and develop the technologies well beyond current CIRM funding and, assuming they are successful, deliver them to patients with unmet medical needs.

Stem cell stories that caught our eye: correcting cystic fibrosis gene, improving IVF outcome, growing bone and Dolly

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.

Cystic Fibrosis gene corrected in stem cells. A team at the University of Texas Medical School at Houston corrected the defective gene that causes cystic fibrosis in stem cells made from the skin of cystic fibrosis patients. In the long term the advance could make it possible to grow new lungs for patients with genes that match their own—with one life-saving exception—and therefore avoid immune rejection. But, the short-term outcome will be a model for the disease that provides tools for evaluating potential new drug therapies.

“We’ve created stem cells corrected for the cystic fibrosis mutation that potentially could be utilized therapeutically for patients,” said Brian Davis the study’s senior author in a university press release. “While much work remains, it is possible that these cells could one day be used as a form of cell therapy.”

The researchers made the genetic correction in the stem cells using the molecular scissors known as zing finger nucleases. Essentially they cut out the bad gene and pasted in the correct version.

Stem cell researchers boost IVF. Given all the ethical issues raised in the early years of embryonic stem cell research it is nice to be able to report on work in the field that can boost the chances of creating a new life through in vitro fertilization (IVF). Building on earlier work at Stanford a CIRM-funded team there has developed a way to detect chromosome abnormalities in the embryo within 30 hours of fertilization.

Chromosomal abnormalities account for a high percent of the 60 to 70 percent of implanted embryos that end up in miscarriage. But traditional methods can’t detect those chromosomal errors until day five or six and clinicians have found that embryos implant best three to four days post fertilization. This new technique should allow doctors to implant only the embryos most likely to survive.

“A failed IVF attempt takes an emotional toll on a woman who is anticipating a pregnancy as well as a financial toll on families, with a single IVF treatment costing thousands and thousands of dollars per cycle. Our findings also bring hope to couples who are struggling to start a family and wish to avoid the selection and transfer of embryos with unknown or poor potential for implantation,” explained Shawn Chavez who led the team and has since moved to Oregon Health Sciences University.

The study, which used recent advanced technology in non-invasive imaging, was described in a press release from Oregon.

Fun TED-Ed video shows how to grow bone. Medical Daily published a story this week about a team that had released a TED-Ed video earlier this month on how to grow a replacement bone on the lab. The embedded video provides a great primer on how we normally grow and repair bone in our bodies and how that knowledge can inform efforts to grow bone in the lab.

In particular, the story walks through a scenario of a patient with a bone defect too large for our normal repair mechanisms to patch up. It describes how scientist can take stem cells from fat, use 3D printers to mold a scaffold the exact shape of the defect, and culture the stem cells on the scaffold in the lab to create the needed bone.

The video and story reflect the work of New York-based company EpiBone and its tissue engineer CEO Nina Tandon.

Happy birthday Dolly (the sheep). July 5 marked the 19th anniversary of the first cloned mammal, Dolly the sheep in Scotland. For fans of the history of science, MotherBoard gives a good brief history of the resulting kerfuffle and a reminder that Dolly was not very healthy and the procedure was not and is not ready to produce cloned human.

Dolly's taxidermied remains are in a museum in Scotland. She died after only six years, about half the normal life expectancy.

Dolly’s taxidermied remains are in a museum in Scotland. She died after only six years, about half the normal life expectancy.

Partnering with Big Pharma to benefit patients

Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs. One way we have been doing that is funding promising research to help it get through what’s called the “Valley of Death.” This is the time between a product or project showing promise and the time it shows that it actually works.

Many times the big pharmaceutical companies or deep pocketed investors, whose support is needed to cover the cost of clinical trials, don’t want to get involved until they see solid proof that this approach works. However, without that support the researchers can’t do the early stage clinical trials to get that proof.

The stem cell agency has been helping get these projects through this Catch 22 of medical research, giving them the support they need to get through the Valley of Death and emerge on the other side where Big Pharma is waiting, ready to take them from there.

We saw more evidence that Big Pharma is increasingly happy doing that this week with the news that the University of California, San Diego, is teaming up with GSK to develop a new approach to treating blood cancers.

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson is leading the UCSD team through her research that aims at killing the cancer stem cells that help tumors survive chemotherapy and other therapies, and then spread throughout the body again. This is work that we have helped fund.

In a story in The San Diego Union Tribune, reporter Brad Fikes says this is a big step forward:

“London-based GSK’s involvement marks a maturation of this aspect of Jamieson’s research from basic science to the early stages of discovering a drug candidate. Accelerating such research is a core purpose of CIRM, founded in 2004 to advance stem cell technology into disease therapies and diagnostics.”

The stem cell agency’s President and CEO, Dr. C. Randal Mills, is also quoted in the piece saying:

“This is great news for Dr. Jamieson and UCSD, but most importantly it is great news for patients. Academic-industry partnerships such as this bring to bear the considerable resources necessary to meaningfully confront healthcare’s biggest challenges. We have been strong supporters of Dr. Jamieson’s work for many years and I think this partnership not only reflects the progress that she has made, but just as importantly it reflects how the field as a whole has progressed.”

As the piece points out, academic researchers are very good at the science but are not always as good at turning the results of the research into a marketable product. That’s where having an industry partner helps. The companies have the experience turning promising therapies into approved treatments.

As Scott Lippman, director of the Moores Cancer Center at UCSD, said of the partnership:

“This is a wonderful example of academia-industry collaboration to accelerate drug development and clinical impact… and opens the door for cancer stem cell targeting from a completely new angle.”

With the cost of carrying out medical research and clinical trials rising it’s hard for scientists with limited funding to go it alone. That’s why these partnerships, with CIRM and industry, are so important. Working together we make it possible to speed up the development and testing of therapies, and get them to patients as quickly as possible.

Share your voice, shape our future

shutterstock_201440705There is power in a single voice. I am always reminded of that whenever I meet a patient advocate and hear them talk about the need for treatments and cures – and not just for their particular disease but for everyone.

The passion and commitment they display in advocating for more research funding reflects the fact that everyday, they live with the consequences of the lack of effective therapies. So as we at CIRM, think about the stem cell agency’s future and are putting together a new Strategic Plan to help shape the direction we take, it only makes sense for us to turn to the patient advocate community for their thoughts and ideas on what that future should look like.

That’s why we are setting up three meetings in the next ten days in San Diego, Los Angeles and San Francisco to give our patient advocates a chance to let us know what they think, in person.

We have already sent our key stakeholders a survey to get their thoughts on the general direction for the Strategic Plan, but there is a big difference between ticking a box and having a conversation. These upcoming meetings are a chance to talk together, to explore ideas and really flesh out the details of what this Strategic Plan could be and should be.

Our President and CEO, Dr. C. Randal Mills wants each of those meetings to be an opportunity to hear, first hand, what people would like to see as we enter our second decade. We have close to one billion dollars left to invest in research so there’s a lot at stake and this is a great chance for patient advocates to help shape our next five years.

Every voice counts, so join us and make sure that yours is heard.

The events are:

San Diego, Monday, July 13th at noon at Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Los Angeles: Tuesday, July 14th at noon at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, 1425 San Pablo Street, 1st floor conf. room Los Angeles, CA 90033

San Francisco: Wednesday, July 15th at noon at CIRM, 210 King Street (3rd floor), San Francisco, CA 94107

There will be parking at each event and a light lunch will be served.

We hope to see you at one of them and if you do plan on coming please RSVP to info@cirm.ca.gov

And of course please feel free to share this invitation to anyone you think might be interested in having their voice heard. We all have a stake in this.

Protein Revs Up Bone Stem Cells; Points Toward Future Osteoporosis Drug

Take a moment to feel your arm and wrist bones. They’re a lot more like solid rock than the soft stretchy skin that covers them. But bone is very much a living tissue continually being broken down and built back up in a process called bone remodeling. In people with osteoporosis, this balance tips toward bone breakdown leading to more porous, fragile bones with increased risk of fractures. An estimated ten million people in the U.S. have osteoporosis accounting for 1.5 million fractures annually at a cost of $17 billion in medical care, not to mention the emotional toll of these often debilitating and even life threatening injuries.

Fluorescent imaging mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

Fluorescent imaging of mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

This week a CIRM-funded research team at UCLA reported in Nature Communications that injection of a human protein called NELL-1 into the blood of mice with osteoporosis-like symptoms tipped the balance back toward bone formation. In a large animal study, delivering NELL-1 directly into the spine also led to increased bone volume. In a university press release, co-senior author Kang Ting spoke of his hopes that these results open up a new therapeutic avenue for treating osteoporosis and other ailments:

“Our end goal is really to harness the bone forming properties of NELL-1 to better treat patients with diverse causes of bone loss, from trauma in military personnel to osteoporosis from age, disease or very weak gravity, which causes bone loss in astronauts.”

In petri dish experiments leading up to these animal results, the research team showed that NELL-1 acts by increasing the specialization of mesenchymal stem cells – a type of adult stem cell found in the bone marrow and fat – into osteoblasts, the cells responsible for building new bone. At the same time, NELL-1 reduced the generation of osteoclasts, the cells responsible for the breakdown, or resorption, of bone. This dual action of NELL-1 explains how it improved the osteoporosis-like symptoms in the animals. Check out this fascinating animation for a visual description of osteoblasts and osteoclasts:

Many of the other molecules that promote bone growth aren’t as efficient as NELL-1: while they increase osteoblast numbers they also increase osteoclasts to some extent. For example, Fosamax is a drug prescribed to women with osteoporosis to help build stronger bones but long-term use has been associated with even more brittle bones and fractures. So this finding with NELL-1 sets it apart and hints at fewer side effects as a therapeutic. Still, it’s known to play a role in brain, cartilage, and blood vessel development so careful studies of non-bone effects are needed as the team pursues a road to the clinic.

For more information about CIRM-funded projects related to osteoporosis, visit our online fact sheet.

Stem Cell Scientists Reconstruct Disease in a Dish; Gain Insight into Deadly Form of Bone Cancer

The life of someone with Li-Fraumeni Syndrome (LFS) is not a pleasant one. A rare genetic disorder that usually runs in families, this syndrome is characterized by heightened risk of developing cancer—multiple types of cancer—at a very young age.

People with LFS, as the syndrome is often called, are especially susceptible to osteosarcoma, a form of bone cancer that most often affects children. Despite numerous research advances, survival rates for this type of cancer have not improved in over 40 years.

shutterstock_142552177 But according to new research from Mount Sinai Hospital and School of Medicine, the prognosis for these patients may not be so dire in a few years.

Reporting today in the journal Cell, researchers describe how they used a revolutionary type of stem cell technology to recreate LFS in a dish and, in so doing, have uncovered the series of molecular triggers that cause people with LFS to have such high incidence of osteosarcoma.

The scientists, led by senior author Ihor Lemischka, utilized induced pluripotent stem cells, or iPSCs, to model LFS—and osteosarcoma—at the cellular level.

Discovered in 2006 by Japanese scientist Shinya Yamanaka, iPSC technology allows scientists to reprogram adult skin cells into embryonic-like stem cells, which can then be turned into virtually any cell in the body. In the case of a genetic disorder, such as LFS, scientists can transform skin cells from someone with the disorder into bone cells and grow them in the lab. These cells will then have the same genetic makeup as that of the original patient, thus creating a ‘disease in a dish.’ We have written often about these models being used for various diseases, particularly neurological ones, but not cancer.

“Our study is among the first to use induced pluripotent stem cells as the foundation of a model for cancer,” said lead author and Mount Sinai postdoctoral fellow Dung-Fang Lee in today’s press release.

The team’s research centered on the protein p53. P53 normally acts as a tumor suppressor, keeping cell divisions in check so as not to divide out of control and morph into early-stage tumors. Previous research had revealed that 70% of people with LFS have a specific mutation in the gene that encodes p53. Using this knowledge and with the help of the iPSC technology, the team shed much-needed light on a molecular link between LFS and bone cancer. According to Lee:

“This model, when combined with a rare genetic disease, revealed for the first time how a protein known to prevent tumor growth in most cases, p53, may instead drive bone cancer when genetic changes cause too much of it to be made in the wrong place.”

Specifically, the team discovered that the ultimate culprit of LFS bone cancer is an overactive p53 gene. Too much p53, it turns out, reduces the amount of another gene, called H19. This then leads to a decrease in the protein decorin. Decorin normally acts to help stem cells mature into healthy, bone-making cells, known as osteoblasts. Without it, the stem cells can’t mature. They instead divide over and over again, out of control, and ultimately cause the growth of dangerous tumors.

But those out of control cells can become a target for therapy, say researchers. In fact, the team found that artificially boosting H19 levels could have a positive effect.

“Our experiments showed that restoring H19 expression hindered by too much p53 restored “protective differentiation” of osteoblasts to counter events of tumor growth early on in bone cancer,” said Lemischka.

And, because mutations in p53 have been linked to other forms of bone cancer, the team is optimistic that these preliminary results will be able to guide treatment for bone cancer patients—whether they have LFS or not. Added Lemischka:

“The work has implications for the future treatment or prevention of LFS-associated osteosarcoma, and possibly for all forms of bone cancer driven by p53 mutations, with H19 and p53 established now as potential targets for future drugs.”

Learn more about how scientists are using stem cell technology to model disease in a dish in our special video series: Stem Cells In Your Face:

Stem cell stories that caught our eye; creating bone, turning data into sound, cord blood and path of a stem cell star

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.

A better ratio of bone to fat
. Most of us at any age would prefer a little less fat and older folks, particularly ones plagued by the bone loss of osteoporosis, could use a bit more bone. Since both types of tissues come from mesenchymal stem cells (MSCs) a team at the University of Miami decided to look for chemical triggers that tells those stem cells whether to become fat or bone.

They found an enzyme that seems to do just that. In mice that were born with a mutation in the gene for that enzyme they saw increased bone growth, less fat production and a leaner body mass. HealthCanal picked up the university’s press release that quoted the leader of the team Joshua Hare:

“The production of bone could have a profound effect on the quality of life for the aging population.”

He goes on to note that there are many hurdles to cross before this becomes a therapeutic reality, but the current work points to lots of potential.

Path to becoming a star stem cell scientist. D, the city magazine for Dallas, published a lengthy—nearly 4,000-word—feature on Sean Morrison, one of the undisputed leaders of our field. While it starts out talking about his latest role of creating a multi-pronged center for innovation at

Sean Morrison

Sean Morrison

Children’s Medical Center Dallas and UT Southwestern, it spends most of its words on how he got there.

It’s fun reading how someone gets into a field as new as stem cell science and what keeps them in the field. Initially, for him it seems to originate from an immense curiosity about what was not known about the powerful little stem cells.

“Fifteen years ago, there was nothing known at the molecular level about how stem cells replicate. And I really felt it was a fundamental question in biology to understand. It was a question that was central to a lot of important issues, because the ability of stem cells to self-renew is critical to form your tissues throughout development, to maintain your tissues throughout adulthood.”

There is also a good retelling of Morrison’s role in the protracted and hard-fought battle to make embryonic stem cell research legal during his years in Michigan. He started working on the campaign to overturn the ban in 2006 and in 2008 the voters agreed. The article makes a compelling case for something I have advocated for years: scientists need to practice speaking for the public and get out and do it.

Turning stem cell data into sound. Interpreting scientific data through sound, sonification, is a bit trendy now. But the concept is quite old. Think of the Geiger counter and the speed of the click changing based on the level of radiation.

Researchers tend to consider sonification when dealing with large data sets that have some level of repetitive component. Following the differentiation of a large number of stem cells as they mature into different types of tissue could lend itself to the genre and a team at Cardiff University in Scotland reports they have succeeded. In doing just that.

HealthCanal picked up the university’s piece talking about the project. Unfortunately it does a very poor job of explaining how the process actually works. I did find this piece on ocean microbes that describes the concept of sonification of data pretty well.

Cord blood poised for greater use. I get very uncomfortable when friends ask for medical advice around stem cells. I usually try to give a lay of the land that comes short of direct advice. A common question centers on the value of paying the annual storage fees to freeze their baby’s cord blood. To which, I typically say that for current uses the value is marginal, but for the uses that could come in five to 10 years, it could be quite significant.

So, it was not surprising to read a headline on a Scientific American Blog last December reading “Vast Majority of Life-Saving Cord Blood Sits Unused.” But it was also fun to read a well-documented counter point guest blog on the site this morning by our former President, Alan Trounson. He suggested a better headline would be: “Vast Majority of Life-Saving Cord Blood Sits Poised for Discovery.”

He details how cord blood has become a valuable research tool and lists some of the FDA-approved clinical trials that could greatly expand the indication of cord blood therapy. While some of those trials will likely produce negative results, some will succeed and they all will start to show how to turn those frozen vials into a more valuable resource.

Goodnight, Stem Cells: How Well Rested Cells Keep Us Healthy

Plenty of studies show that a lack of sleep is nothing but bad news and can contribute to a whole host of health problems like heart disease, poor memory, high blood pressure and obesity.

HSCs_Sleeping_graphic100x100

Even stem cells need rest to stay healthy

In a sense, the same holds true for the stem cells in our body. In response to injury, adult stem cells go to work by dividing and specializing into the cells needed to heal specific tissues and organs. But they also need to rest for long-lasting health. Each cell division carries a risk of introducing DNA mutations—and with it, a risk for cancer. Too much cell division can also deplete the stem cell supply, crippling the healing process. So it’s just as important for the stem cells to assume an inactive, or quiescent, state to maintain their ability to mend the body. Blood stem cells for instance are mostly quiescent and only divide about every two months to renew their reserves.

Even though the importance of this balance is well documented, exactly how it’s achieved is not well understood; that is, until now. Earlier this week, a CIRM-funded research team from The Scripps Research Institute (TSRI) reported on the identification of an enzyme that’s key in controlling the work-rest balance in blood stem cells, also called hematopoietic stem cells (HSCs). Their study, published in the journal Blood, could point the way to drugs that treat anemias, blood cancers, and other blood disorders.

Previous studies in other cell types suggested that this key enzyme, called ItpkB, might play a role in promoting a rested state in HSCs. Senior author Karsten Sauer explained their reasoning for focusing on the enzyme in a press release:

“What made ItpkB an attractive protein to study is that it can dampen activating signaling in other cells. We hypothesized that ItpkB might do the same in HSCs to keep them at rest. Moreover, ItpkB is an enzyme whose function can be controlled by small molecules. This might facilitate drug development if our hypothesis were true.”

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

Senior author Karsten Sauer is an associate professor at The Scripps Research Institute.

To test their hypothesis, the team studied HSCs in mice that completely lacked ItpkB. Sure enough, without ItpkB the HSCs got stuck in the “on” position and continually multiplied until the supply of HSCs stores in the bone marrow were exhausted. Without these stem cells, the mice could no longer produce red blood cells, which deliver oxygen to the body or white blood cells, which fight off infection. As a result the animals died due to severe anemia and bone marrow failure. Sauer used a great analogy to describe the result:

“It’s like a car—you need to hit the gas pedal to get some activity, but if you hit it too hard, you can crash into a wall. ItpkB is that spring that prevents you from pushing the pedal all the way through.”

With this new understanding of how balancing stem cell activation and deactivation works, Sauer and his team have their sights set on human therapies:

“If we can show that ItpkB also keeps human HSCs healthy, this could open avenues to target ItpkB to improve HSC function in bone marrow failure syndromes and immunodeficiencies or to increase the success rates of HSC transplantation therapies for leukemias and lymphomas.”

Stem cell stories that caught our eye; drug screening, aging stem cells in brain repair and blood diseases

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.

Heart-on-a-chip used to screen drugs. With CIRM funding, a team at the University of California, Berkeley, has used stem cell technology to create a virtual heart on an inch-long piece of silicon. The cells in that “chip” mimic the physiology of a human heart and have shown that they can accurately show how drugs will impact the heart.
HeartChip4196107801
Starting with iPS-type stem cells made from reprogramming adult cells the researchers grew them into heart muscle that could beat and align in multiple layers with microscopic channels that mimic blood vessels. They tested three drugs currently used to treat heart disease and found the changes seen in the heart-on-a-chip were consistent with what is seen in patients. For example, they tested isoproterenol, a drug used to treat slow heart rate and saw a dramatic increase in heart rate.

But the real value in the silicon-housed heart will be in screening potential new drugs and finding out adverse impacts before taking them into costly human clinical trials. Genetic Engineering & Biotechnology News wrote up the work and quoted a member of the team, Kevin Healy:

“It takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market.”

Brain stem cell activity decreases with age. We have known for some time that the adult stem cells that reside in most of our tissues and spend our lives repairing those tissues are less effective as we age. But the stemness of those cells—their ability to regenerate themselves—has not generally been questioned, rather we have assumed they just lost some of their ability to mature into the type of cell needed to make the repair.

Now, a team at the Ludwig-Maximilians-Universitat in Munich has published data suggesting that brain stem cells over time loose both their ability to renew themselves and some of their ability to become certain kinds of nerves. ScienceDaily picked up a press release from the institution and it quoted one of the authors, Magdalena Gotz, on the implications of their finding for therapy.

“In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time.”

Another alternative for correcting genetic blood disease. CIRM funds a few programs that are trying to treat blood diseases such as sickle cell anemia and beta thalassemia by genetically altering blood forming stem cells. The goal being to correct defects in the gene for hemoglobin, the protein that carries oxygen in red blood cells.

Instead of starting with a patient’s own blood stem cells, which can require a somewhat traumatic harvest procedure, a new approach by a team at the Salk Institute in La Jolla creates iPS type stem cells by reprogramming the cells in a small skin sample. They mature those into blood stem cells and genetically modify them so that they can produce red blood cells that have the correct hemoglobin.

The Salk team uses a modified cold virus to carry the gene into the cell. ScienceDaily picked up the institute’s press release, which quotes one of the co-first authors on the study Mo Li on how the process works:

“It happens naturally, working like a zipper. The good gene just zips in perfectly, pushing the bad one out.”

CIRM funds other work by the senior author, Juan Carlos Izpisua Belmonte, but not this project. Because you never know which technology is going to work out best in the long term, it is nice to see other funders stepping up and pushing this alternative forward.

One-Time, Lasting Treatment for Sickle Cell Disease May be on Horizon, According to New CIRM-Funded Study

For the nearly 1,000 babies born each year in the United States with sickle cell disease, a painful and arduous road awaits them. The only cure is to find a bone marrow donor—an exceedingly rare proposition. Instead, the standard treatment for this inherited blood disorder is regular blood transfusions, with repeated hospitalizations to deal with complications of the disease. And even then, life expectancy is less than 40 years old.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

But now, scientists at UCLA are offering up a potentially superior alternative: a new method of gene therapy that can correct the genetic mutation that causes sickle cell disease—and thus help the body on its way to generate normal, healthy blood cells for the rest of the patient’s life. The study, funded in part by CIRM and reported in the journal Blood, offers a great alternative to developing a functional cure for sickle cell disease. The UCLA team is about to begin a clinical trial with another gene therapy method, so they—and their patients—will now have two shots on goal in their effort to cure the disease.

Though sickle cell disease causes dangerous changes to a patient’s entire blood supply, it is caused by one single genetic mutation in the beta-globin gene—altering the shape of the red blood cells from round and soft to pointed and hard, thus resembling a ‘sickle’ shape for which the disease is named. But the UCLA team, led by Donald Kohn, has now developed two methods that can correct the harmful mutation. As he explained in a UCLA news release about the newest technique:

“[These results] suggest the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code. Since sickle cell disease was the first human genetic disease where we understood the fundamental gene defect, and since everyone with sickle cell has the exact same mutation in the beta-globin gene, it is a great target for this gene correction method.”

The latest gene correction technique used by the team uses special enzymes, called zinc-finger nucleases, to literally cut out and remove the harmful mutation, replacing it with a corrected version. Here, Kohn and his team collected bone marrow stem cells from individuals with sickle cell disease. These bone marrow stem cells would normally give rise to sickle-shaped red blood cells. But in this study, the team zapped them with the zinc-finger nucleases in order to correct the mutation.

Then, the researchers implanted these corrected cells into laboratory mice. Much to their amazement, the implanted cells began to replicate—into normal, healthy red blood cells.

Kohn and his team worked with Sangamo BioSciences, Inc. to design the zinc-finger nucleases that specifically targeted and cut the sickle-cell mutation. The next steps will involve improving the efficiency and safest of this method in pre-clinical animal models, before moving into clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said UCLA graduate student Megan Hoban, the study’s first author. “The study data provide the foundational evidence that the method is viable.”

This isn’t the first disease for which Kohn’s team has made significant strides in gene therapy to cure blood disorders. Just last year, the team announced a promising clinical trial to cure Severe Combined Immunodeficiency Syndrome, also known as SCID or “Bubble Baby Disease,” by correcting the genetic mutation that causes it.

While this current study still requires more research before moving into clinical trials, Kohn and his team announced last month that their other gene therapy method, also funded by CIRM, has been approved to start clinical trials. Kohn argues that it’s vital to explore all promising treatment options for this devastating condition:

“Finding varied ways to conduct stem cell gene therapies is important because not every treatment will work for every patient. Both methods could end up being viable approaches to providing one-time, lasting treatments for sickle cell disease and could also be applied to the treatment of a large number of other genetic diseases.”

Find Out More:
Read first-hand about Sickle Cell Disease in our Stories of Hope series.
Watch Donald Kohn speak to CIRM’s governing Board about his research.