How a see-through fish could one day lead to substitutes for bone marrow transplants

Human blood stem cells

For years researchers have struggled to create human blood stem cells in the lab. They have done it several times with animal models, but the human kind? Well, that’s proved a bit trickier. Now a CIRM-funded team at UC San Diego (UCSD) think they have cracked the code. And that would be great news for anyone who may ever need a bone marrow transplant.

Why are blood stem cells important? Well, they help create our red and white blood cells and platelets, critical elements in carrying oxygen to all our organs and fighting infections. They have also become one of the most important weapons we have to combat deadly diseases like leukemia and lymphoma. Unfortunately, today we depend on finding a perfect or near-perfect match to make bone marrow transplants as safe and effective as possible and without a perfect match many patients miss out. That’s why this news is so exciting.

Researchers at UCSD found that the process of creating new blood stem cells depends on the action of three molecules, not two as was previously thought.

Zebrafish

Here’s where it gets a bit complicated but stick with me. The team worked with zebrafish, which use the same method to create blood stem cells as people do but also have the advantage of being translucent, so you can watch what’s going on inside them as it happens.  They noticed that a molecule called Wnt9a touches down on a receptor called Fzd9b and brings along with it something called the epidermal growth factor receptor (EGFR). It’s the interaction of these three together that turns a stem cell into a blood cell.

In a news release, Stephanie Grainger, the first author of the study published in Nature Cell Biology, said this discovery could help lead to new ways to grow the cells in the lab.

“Previous attempts to develop blood stem cells in a laboratory dish have failed, and that may be in part because they didn’t take the interaction between EGFR and Wnt into account.”

If this new approach helps the team generate blood stem cells in the lab these could be used to create off-the-shelf blood stem cells, instead of bone marrow transplants, to treat people battling leukemia and/or lymphoma.

CIRM is also funding a number of other projects, several in clinical trials, that involve the use of blood stem cells. Those include treatments for: Beta Thalassemia; blood cancer; HIV/AIDS; and Severe Combined Immunodeficiency among others.

CIRM Board Approves Funding for New Clinical Trials in Solid Tumors and Pediatric Disease

Dr. Theodore Nowicki, physician in the division of pediatric hematology/oncology at UCLA. Photo courtesy of Milo Mitchell/UCLA Jonsson Comprehensive Cancer Center

The governing Board of the California Institute for Regenerative Medicine (CIRM) awarded two grants totaling $11.15 million to carry out two new clinical trials.  These latest additions bring the total number of CIRM funded clinical trials to 53. 

$6.56 Million was awarded to Rocket Pharmaceuticals, Inc. to conduct a clinical trial for treatment of infants with Leukocyte Adhesion Deficiency-I (LAD-I)

LAD-I is a rare pediatric disease caused a mutation in a specific gene that affects the body’s ability to combat infections.  As a result, infants with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations.  Those that survive infancy experience recurrent severe infections, with mortality rates for severe LAD-I at 60-75% prior to the age of two and survival very rare beyond the age of five.

Rocket Pharmaceuticals, Inc. will test a treatment that uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient that would give rise to functional immune cells, thereby enabling the body to combat infections.  

The award is in the form of a CLIN2 grant, with the goal of conducting a clinical trial to assess the safety and effectiveness of this treatment in patients with LAD-I.

This project utilizes a gene therapy approach, similar to that of three other clinical trials funded by CIRM and conducted at UCLA by Dr. Don Kohn, for X-linked Chronic Granulomatous Disease, an inherited immune deficiency “bubble baby” disease known as ADA-SCID, and Sickle Cell Disease.

An additional $4.59 million was awarded to Dr. Theodore Nowicki at UCLA to conduct a clinical trial for treatment of patients with sarcomas and other advanced solid tumors. In 2018 alone, an estimated 13,040 people were diagnosed with soft tissue sarcoma (STS) in the United States, with approximately 5,150 deaths.  Standard of care treatment for sarcomas typically consists of surgery, radiation, and chemotherapy, but patients with late stage or recurring tumor growth have few options.

Dr. Nowicki and his team will genetically modify peripheral blood stem cells (PBSCs) and peripheral blood monocular cells (PBMCs) to target these solid tumors. The gene modified stem cells, which have the ability to self-renew, provide the potential for a durable effect.

This award is also in the form of a CLIN2 grant, with the goal of conducting a clinical trial to assess the safety of this rare solid tumor treatment.

This project will add to CIRM’s portfolio in stem cell approaches for difficult to treat cancers.  A previously funded a clinical trial at UCLA uses this same approach to treat patients with multiple myeloma.  CIRM has also previously funded two clinical trials using different approaches to target other types of solid tumors, one of which was conducted at Stanford and the other at UCLA. Lastly, two additional CIRM funded trials conducted by City of Hope and Poseida Therapeutics, Inc. used modified T cells to treat brain cancer and multiple myeloma, respectively.

“CIRM has funded 23 clinical stage programs utilizing cell and gene medicine approaches” says Maria T. Millan, M.D., the President and CEO of CIRM. “The addition of these two programs, one in immunodeficiency and the other for the treatment of malignancy, broaden the scope of unmet medical need we can impact with cell and gene therapeutic approaches.”

Stanford scientist uses CRISPR-Cas9 and stem cells to develop potential “bubble baby” therapy

Dr. Matthew Porteus, professor of pediatrics at Stanford University.
Photo courtesy of Stanford Medicine.

Our immune system is an important and essential part of everyday life. It is crucial for fighting off colds and, with the help of vaccinations, gives us immunity to potentially lethal diseases. Unfortunately, for some infants, this innate bodily defense mechanism is not present or is severely lacking in function.

This condition is known as severe combined immunodeficiency (SCID), commonly nicknamed “bubble baby” disease because of the sterile plastic bubble these infants used to be placed in to prevent exposure to bacteria, viruses, and fungi that can cause infection. There are several forms of SCID, one of which involves a single genetic mutation on the X chromosome and is known as SCID-X1

Many infants with SCID-X1 develop chronic diarrhea, a fungal infection called thrush, and skin rashes. Additionally, these infants grow slowly in comparison to other children. Without treatment, many infants with SCID-X1 do not live beyond infancy.

SCID-X1 occurs almost predominantly in males since they only carry one X chromosome, with at least 1 in 50,000 baby boys born with this condition. Since females carry two X chromosomes, one inherited from each parent, they are unlikely to inherit two X chromosomes with the mutation present since it would require the father to have SCID-X1.

What if there was a way to address this condition by correcting the single gene mutation? Dr. Matthew Porteus at Stanford University is leading a study that has developed an approach to treat SCID-X1 that utilizes this concept.

By using CRISPR-Cas9 technology, which we have discussed in detail in a previous blog post, it is possible to delete a problematic gene and insert a corrected gene. Dr. Porteus and his team are using CRISPR-Cas9 to edit blood stem cells, which give rise to immune cells, which are the foundation of the body’s defense mechanism. In a study published in Nature, Dr. Porteus and his team have demonstrated proof of concept of this approach in an animal model.

The Stanford team was able to take blood stem cells from six infants with SCID-X1 and corrected them with CRISPR-Cas9. These corrected stem cells were then introduced into mice modeled to have SCID-X1. It was found that these mice were not only able to make immune cells, but many of the edited stem cells maintained their ability to continuously create new blood cells.

In a press release, Dr. Mara Pavel-Dinu, a member of the research team, said:

“To our knowledge, it’s the first time that human SCID-X1 cells edited with CRISPR-Cas9 have been successfully used to make human immune cells in an animal model.”

CIRM has previously awarded Dr. Porteus with a preclinical development award aimed at developing gene correction therapy for blood stem cells for SCID-X1. In addition to this, CIRM has funded two other projects conducted by Dr. Porteus related to CRISPR-Cas9. One of these projects used CRISPR-Cas 9 to develop a treatment for chronic sinusitis due to cystic fibrosis and the second project used the technology to develop an approach for treating sickle cell disease.

CIRM has also funded four clinical trials related to SCID. Two of these trials are related to SCID-X1, one being conducted at St. Jude Children’s Research Hospital and the other at Stanford University. The third trial is related to a different form of SCID known as ADA-SCID and is being conducted at UCLA in partnership with Orchard Therapeutics. Finally, the last of the four trials is related to an additional form of SCID known as ART-SCID and is being conducted at UCSF.

Stories that Caught Our Eye: New ways to heal old bones; and keeping track of cells once they are inside you

broken bones

How Youth Factor Can Help Repair Old Bones

As we get older things that used to heal quickly tend to take a little longer to get better. In some cases, a lot longer. Take bones for example. A fracture in someone who is in their 70’s often doesn’t heal as quickly, or completely, as in someone much younger. For years researchers have been working on ways to change that. Now we may be one step closer to doing just that.

We know that using blood stem cells can help speed up healing for bone fractures (CIRM is funding work on that) and now researchers at Duke Health believe they have figured out how that works.

The research, published in the journal Nature Communications, identifies what the Duke team call the “youth factor” inside bone marrow stem cells. It’s a type of white blood cell called a macrophage. They say the proteins these macrophages produce help stimulate bone repair.

In a news story in Medicine News Line  Benjamin Alman, senior author on the study, says:

“While macrophages are known to play a role in repair and regeneration, prior studies do not identify secreted factors responsible for the effect. Here we show that young macrophage cells play a role in the rejuvenation process, and injection of one of the factors produced by the young cells into a fracture in old mice rejuvenates the pace of repair. This suggests a new therapeutic approach to fracture rejuvenation.”

Next step, testing this in people.

A new way to track stem cells in the body

It’s one thing to transplant stem cells into a person’s body. It’s another to know that they are going to go where you want them to and do what you want them to. University of Washington researchers have invented a device that doesn’t just track where the cells end up, but also what happens to them along the way.

The device is called “CellTagging”, and in an article in Health Medicine Network, Samantha Morris, one of the lead researchers says this could help in better understanding how to use stem cells to grow replacement tissues and organs.

“There is a lot of interest in the potential of regenerative medicine — growing tissues and organs in labs — to test new drugs, for example, or for transplants one day. But we need to understand how the reprogramming process works. We want to know if the process for converting skin cells to heart cells is the same as for liver cells or brain cells. What are the special conditions necessary to turn one cell type into any other cell type? We designed this tool to help answer these questions.”

In the study, published in the journal Nature, the researchers explain how they use a virus to insert tiny DNA “barcodes” into cells and that as the cells travel through the body they are able to track them.

Morris says this could help scientists better understand the conditions needed to more effectively program cells to do what we want them to.

“Right now, cell reprogramming is really inefficient. When you take one cell population, such as skin cells, and turn it into a different cell population — say intestinal cells — only about 1 percent of cells successfully reprogram. And because it’s such a rare event, scientists have thought it is likely to be a random process — there is some correct set of steps that a few cells randomly hit upon. We found the exact opposite. Our technology lets us see that if a cell starts down the right path to reprogramming very early in the process, all of its related sibling cells and their descendants are on the same page, doing the same thing.”

New hope for stem cell therapy in patients with leukemia

LeukemiaWhiteBloodCell

Leukemia white blood cell

Of the many different kinds of cancer that affect humans, leukemia is the most common in young people. As with many types cancer, doctors mostly turn to chemotherapy to treat patients. Chemotherapy, however, comes with its own share of issues, primarily severe side effects and the constant threat of disease recurrence.

Stem cell therapy treatment has emerged as a potential cure for some types of cancer, with leukemia patients being among the first groups of patients to receive this type of treatment. While exciting because of the possibility of a complete cure, stem cell therapy comes with its own challenges. Let’s take a closer look.

Leukemia is characterized by abnormal white blood cells (also known as the many different types of cells that make up our immune system) that are produced at high levels. Stem cell therapy is such an appealing treatment option because it involves replacing the patient’s aberrant blood stem cells with healthy ones from a donor, which provides the possibility of complete and permanent remission for the patient.

Unfortunately, in approximately half of patients who receive this therapy, the donor cells (which turn into immune cells), can also destroy the patients healthy tissue (i.e. liver, skin etc…), because the transplanted blood stem cells recognize patient’s tissue as foreign. While doctors try to lessen this type of response (also known as graft versus host disease (GVHD)), by suppressing the patient’s immune system, this procedure lessens the effectiveness of the stem cell therapy itself.

Now scientists at the University of Zurich have made an important discovery – published in the journal Science Translational Medicine – that could mitigate this potentially fatal response in patients. They found that a molecule called GM-CSF, is a critical mediator of the severity of GVHD. Using a mouse model, they showed that if the donor cells were unable to produce GM-CSF, then mice fared significantly better both in terms of less damage to tissues normally affected by GVHD, such as the skin, and overall survival.

While exciting, the scientists were concerned about narrowing in on this molecule as a potential target to lessen GVHD, because GM-CSF, an important molecule in the immune system, might also be important for ensuring that the donor immune cells do their jobs properly. Reassuringly, the researchers found that blocking GM-CSF’s function had no effect on the ability of the donor cells to exert their anti-cancer effect. This was surprising because previously the ability of donor cells to cause GVHD, versus protect patients from the development of cancer was thought to occur via the same biological mechanisms.

Most excitingly, however, was that finding that high levels of GM-CSF are also observed in patient samples, and that the levels of GM-CSF correlate to the severity of GVHD. Dr. Burkhard Becher and his colleagues, the authors of this study, now want to run a clinical trial to determine whether blocking GM-CSF blocks GVHD in humans like it does in mice. In a press release, Dr. Becher states the importance of these findings:

“If we can stop the graft-versus-host response while preserving the anti-cancer effect, this procedure can be employed much more successfully and with fewer risks to the patient. This therapeutic strategy holds particular promise for patients with the poorest prognosis and highest risk of fatality.”

Support cells have different roles in blood stem cell maintenance before and after stress

How-Stem-Cells-Act-When-Stressed-Versus-When-At-Rest

Expression of pleiotrophin (green) in bone marrow blood vessels (red) and stromal cells (white) in normal mice (left), and in mice 24 hours after irradiation (right). UCLA Broad Stem Cell Research Center/Cell Stem Cell

A new study published in the journal Cell Stem Cell, reveals how different types of cells in the bone marrow are responsible for supporting blood stem cell maintenance before and after injury.

It was already well known in the field that two different cell types, namely endothelial cells (which line blood vessels) and stromal cells (which make up connective tissue, or tissue that provides structural support for any organ), are responsible for maintaining the population of blood stem cells in the bone marrow. However, how these cells and the molecules they secrete impact blood stem cell development and maintenance is not well understood.

Hematopoietic stem cells are responsible for generating the multiple different types of cells found in blood, from our oxygen carrying red blood cells to the many different types of white blood cells that make up our immune system.

Dr. John Chute’s group at UCLA had previously discovered that a molecule called pleiotrophin, or PTN, is important for promoting self-renewal of the blood stem cell population. They did not, however, understand which cells secrete this molecule and when.

To answer this question, the scientists developed mouse models that did not produce PTN in different types of bone marrow cells, such as endothelial cells and stromal cells. Surprisingly, they saw that the inability of stromal cells to produce PTN decreased the blood stem cell population, but deletion of PTN in endothelial cells did not affect the blood stem cell niche.

Even more interestingly, the researchers found that in animals that were subjected to an environmental stressor, in this case, radiation, the result was reversed: endothelial cell PTN was necessary for blood stem cell renewal, whereas stromal cell PTN was not. While an important part of the knowledge base for blood stem cell biology, the reason for this switch in PTN secretion at times of homeostasis and disease is still unknown.

As Dr. Chute states in a press release, this result could have important implications for cancer treatments such as radiation:

“It may be possible to administer modified, recombinant versions of pleiotrophin to patients to accelerate blood cell regeneration. This strategy also may apply to patients undergoing bone marrow transplants.”

Another important consideration to take away from this work is that animal models developed in the laboratory should take into account the possibility that blood stem cell maintenance and regeneration is distinctly controlled under healthy and disease state. In other words, cellular function in one state is not always indicative of its role in another state.

This work was partially funded by a CIRM Leadership Award.

 

 

Stem cell gene therapy combination could help children battling a rare genetic disorder

Hunter Syndrome-2

A child with Hunter Syndrome

Hunter syndrome is devastating. It’s caused by a single enzyme, IDS, that is either missing or malfunctioning. Without the enzyme the body is unable to break down complex sugar molecules and as those build up they cause permanent, progressive damage to the body and brain and, in some instances, result in severe mental disabilities. There is no cure and existing treatments are limited and expensive.

But now researchers at the University of Manchester in England have developed an approach that could help children – the vast majority of them boys – suffering from Hunter syndrome.

Working with a mouse model of the disease the researchers took some blood stem cells from the bone marrow and genetically re-engineered them to correct the mutation that caused the problem. They also added a “tag” to the IDS enzyme to help it more readily cross the blood brain barrier and deliver the therapy directly to the brain.

In a news release Brian Bigger, the lead researcher of the study published in EMBO Molecular Medicine, said the combination therapy helped correct bone, joint and brain disease in the mice.

“We expected the stem cell gene therapy approach to deliver IDS enzyme to the brain, as we have shown previously for another disease: Sanfilippo types A and B, but we were really surprised to discover how much better the tag made the therapy in the brain. It turns out that the tag didn’t only improve enzyme uptake across the blood brain barrier, but also improved uptake of the enzyme into cells and it appeared to be more stable in the bloodstream – all improvements on current technology.”

While the results are very encouraging it is important to remember the experiment was done in mice. So, the next step is to see if this might also work in people.

Joshua Davies has made a video highlighting the impact Hunter syndrome has on families: it’s called ‘Living Beyond Hope’

Fish umbrellas and human bone: protecting blood stem cells from the sun’s UV rays

Blood stem cells.jpg

Most people probably do not question the fact that human blood stem cells – those that give rise to all the cells in our blood – live inside the marrow of our bones, called a stem cell “niche”. But it is pretty odd when you stop to think about it. I mean, it makes sense that the hard, calcium-rich structure of bones provide our bodies with a skeleton but why is it also responsible for making our blood?

This week, researchers at Harvard report in Nature that the answer may come down to protecting these precious cells from the DNA-damaging effects of UV radiation from the sun. They arrived at those insights by examining zebrafish which harbor blood stem cells, not in their bones, but in their kidneys. Fredrich Kapp, MD, the first author of the report, was trying to analyze blood stem cells in zebrafish under the microscope but noticed a layer of other cells on top of the kidney was obscuring his view.

fishumbrella

In a zebrafish larva (illustration above), a dark umbrella formed by pigmented cells (white arrows point to these black spots in box, left) in the kidney protects vulnerable stem cells from damaging UV light. Right image is a closeup of the box. Scale bars equal 100 micrometers (left) and 50 micrometers (right). Credit: F. Kapp et al./Nature 2018
Read more at: https://phys.org/news/2018-06-blood-cells-bones.html#jCp

That layer of cells turned out to be melanocytes which produce melanin a pigment that gives our skin color. Melanin also protects our skin cells from the sun’s UV radiation which damages our DNA and can cause genetic mutations. In a press release, Kapp recalled his moment of insight:

“The shape of the melanocytes above the kidney reminded me of a parasol, so I thought, do they provide UV protection to blood stem cells?”

To answer his question, he and his colleagues compared the effects of UV radiation on normal zebrafish versus mutant zebrafish lacking the layer of melanocytes. Confirming Kapp’s hypothesis, the fish missing the melanocyte layer had fewer blood stem cells. Simply turning the normal fish upside down and exposing them to the UV rays also depleted the blood stem cells.

And here’s where the story gets really cool. In studying frogs – animals closer to us on the evolutionary tree – they found that as the tadpole begins to grow legs, their blood stem cells migrate from the melanocyte-covered kidney cells to inside the bone marrow, an even better form of UV protection. Senior author Leonard Zon explained the importance of this finding:

“We now have evidence that sunlight is an evolutionary driver of the blood stem cell niche. As a hematologist and oncologist, I treat patients with blood diseases and cancers. Once we understand the niche better, we can make blood stem cell transplants much safer.”

 

 

Friday Roundup: A better kind of blood stem cell transplant; Encouraging news from spinal cord injury trial; Finding an “elusive” cell that could help diabetics

Cool Instagram image of the week:

Pancreatic Progenitors

Diabetes Research Institute scientists have confirmed that the unique stem cells reside within large ducts of the human pancreas. Two such ducts (green) surrounded by three islets (white) are shown. [Diabetes Research Institute Foundation]

Chemo- and radiation-free blood stem cell transplant showing promise

Bubble baby disease, also known as severe combined immunodeficiency (SCID), is an inherited disorder that leaves newborns without an effective immune system. Currently, the only approved treatment for SCID is a blood stem cell transplant, in which the patient’s defective immune system cells are eliminated by chemotherapy or radiation to clear out space for cells from a healthy, matched donor. Even though the disease can be fatal, physicians loathe to perform a stem cell transplant on bubble baby patients:

Shizuru“Physicians often choose not to give chemotherapy or radiation to young children with SCID because there are lifelong effects: neurological impairment, growth delays, infertility, risk of cancer, etc.,” says Judith Shizuru, MD, PhD, professor of medicine at Stanford University.

To avoid these complications, Dr. Shizuru is currently running a CIRM-funded clinical trial testing a gentler approach to prepare patients for blood stem cell transplants. She presented promising, preliminary results of the trial on Tuesday at the annual meeting of Stanford’s Center for Definitive and Curative Medicine.

Trial participants are receiving a protein antibody called CD117 before their stem cell transplant. Previous studies in animals showed that this antibody binds to the surface of blood stem cells and blocks the action of a factor which is required for stem cell survival. This property of CD117 provides a means to get rid of blood stem cells without radiation or chemotherapy.

Early results in two participants indicate that, 6 and 9 months after receiving the CD117 blood stem cell transplants, the donor cells have successfully established themselves in the patients and begun making immune cells.

Spinal cord injury trial reports more promising results:

AsteriasRegular readers of our blog will already know about our funding for the clinical trial being run by Asterias Biotherapeutics to treat spinal cord injuries. The latest news from the company is very encouraging, in terms of both the safety and effectiveness of the treatment.

Asterias is transplanting stem cells into patients who have suffered recent injuries that have left them paralyzed from the neck down. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling in their hands and arms.

This week the company announced that of the 25 patients they have treated there have been no serious side effects. In addition:

  • Magnetic Resonance Imaging (MRI) scans show that in more than 90 percent of the patients the cells appear to show signs of engraftment
  • At least 75 percent of those treated have recovered at least one motor level, and almost 20 percent have recovered two levels

In a news release, Michael Mulroy, Asterias’ President and CEO, said:

“The positive safety profile to date, the evidence supporting engraftment of the cells post-implantation, and the improvements we are seeing in upper extremity motor function highlight the promising findings coming from this Phase 1/2a clinical trial, which will guide us as we work to design future studies.”

There you are! Finding the “elusive” human pancreatic progenitor cells – the story behind our cool Instagram image of the week.

Don’t you hate it when you lose something and can’t find it? Well imagine the frustration of scientists who were looking for a group of cells they were sure existed but for decades they couldn’t locate them. Particularly as those cells might help in developing new treatments for diabetes.

Diabetes-Research-Institute_University-of-Miami-Miller-School-of-MedicineWell, rest easy, because scientists at the Diabetes Research Institute at the University of Miami finally found them.

In a study, published in Genetic Engineering and Biotechnology News, the researchers show how they found these progenitor cells in the human pancreas, tucked away in the glands and ducts of the organ.

In type 1 diabetes, the insulin-producing cells in the pancreas are destroyed. Finding these progenitor cells, which have the ability to turn into the kinds of cells that produce insulin, means researchers could develop new ways to regenerate the pancreas’ ability to function normally.

That’s a long way away but this discovery could be an important first step along that path.

Using the AIDS virus to help children battling a deadly immune disorder

Ronnie Kashyap, patient in SCID clinical trial: Photo Pawash Priyank

More than 35 million people around the world have been killed by HIV, the virus that causes AIDS. So, it’s hard to think that the same approach the virus uses to infect cells could also be used to help children battling a deadly immune system disorder. But that’s precisely what researchers at UC San Francisco and St. Jude Children’s Research Hospital are doing.

The disease the researchers are tackling is a form of severe combined immunodeficiency (SCID). It’s also known as ‘bubble baby’ disease because children are born without a functioning immune system and in the past were protected from germs within the sterile environment of a plastic bubble. Children with this disease often die of infections, even from a common cold, in the first two years of life.

The therapy involves taking the patient’s own blood stem cells from their bone marrow, then genetically modifying them to correct the genetic mutation that causes SCID. The patient is then given low-doses of chemotherapy to create space in their bone marrow for the news cells. The gene-corrected stem cells are then transplanted back into the infant, creating a new blood supply and a repaired immune system.

Unique delivery system

The novel part of this approach is that the researchers are using an inactivated form of HIV as a means to deliver the correct gene into the patient’s cells. It’s well known that HIV is perfectly equipped to infiltrate cells, so by taking an inactivated form – meaning it cannot infect the individual with HIV – they are able to use that infiltrating ability for good.

The results were announced at the American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta.

The researchers say seven infants treated and followed for up to 12 months, have all produced the three major immune system cell types affected by SCID. In a news release, lead author Ewelina Mamcarz, said all the babies appear to be doing very well:

“It is very exciting that we observed restoration of all three very important cell types in the immune system. This is something that’s never been done in infants and a huge advantage over prior trials. The initial results also suggest our approach is fundamentally safer than previous attempts.”

One of the infants taking part in the trial is Ronnie Kashyap. We posted a video of his story on our blog, The Stem Cellar.

If the stem cell-gene therapy combination continues to show it is both safe and effective it would be a big step forward in treating SCID. Right now, the best treatment is a bone marrow transplant, but only around 20 percent of infants with SCID have a sibling or other donor who is a good match. The other 80 percent have to rely on a less well-matched bone marrow transplant – usually from a parent – that can still leave the child prone to life-threatening infections or potentially fatal complications such as graft-versus-host disease.

CIRM is funding two other clinical trials targeting SCID. You can read about them here and here.