Tag Archives: brain

Research Roundup: 3D printed ovaries, social ties and longevity, a new bone regeneration therapy, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • 3D printed ovaries produce healthy offspring in mice. In a proof of principle experiment, scientists have succeeded in removing and replacing a mouse’s ovary with a bioprosthetic replacement. These 3D printed ovaries housed immature mouse eggs, permitting the mice to ovulate and to also give birth to healthy pups. These mice were also able to successfully nurse their pups.The 3D printed ovaries were made of gelatin and is safe to use in humans. This research is highly applicable to “women who have undergone adult cancer treatments or those who survived childhood cancer and now have increased risks of infertility and hormone-based developmental issues.” This paper was published in Nature communications.

  • New study investigating how the brain encodes fear memory could lead to novel therapeutics aimed at reducing pathological fear in PTSD. Using mice, a tracing method which highlights neurons in the brain in different colors, electrophysical and optogenetic methods — these researchers that as much as 17% of neurons projecting to the hippocampus also projected to the amygdala and the mPFC. The authors explained “that the acquisition (encoding) and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, amygdala and mPFC. The hippocampus encodes context cues, the amygdala stores associations between a context and an aversive event, and the mPFC signals whether a defensive response is appropriate in the present context.” This study was published in the Journal of Neuroscience.
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Mouse hippocampal neuron projections. Source: Journal of Neuroscience.

  • A simple blood test detects radiation exposure in nonhuman primates. A report in the Science Translational Medicine describes how levels of three microRNAs (miRNAs, which are small non-coding RNA molecules found in plants and animals that regulate gene expression) can be detected in blood and other bodily fluids with 100% accuracy. Two other miRNAs can predict whether the radiation exposure will be fatal. This new development could help triage victims of nuclear disasters, like the one in Fukushima, Japan, in 2011. The assay could be deployed in the field with limited expertise or equipment.
  • Large families and strong social ties help animals live longer. A large study of a naturalistic population of rhesus monkeys on an island off of Puerto Rico shows that adult monkeys with more relatives in their social network have a better life expectancy. Rhesus monkeys live in matriarchal societies, meaning that families are formed around adult females and their offspring and other relatives. By examining demographic data on over 900 monkeys across a 21 year period, researchers found that each extra female relative reduced a prime-aged female macaque’s chances of dying in one year by 2.3%. Because humans and rhesus monkeys shared a common ancestor about 25 million years ago, “we can take clues from these distant cousins about how humans might have existed in pre-industrial societies,” said Dr. Laurent Brent, Leverhulme Early Career Fellow and Lecturer at the University of Exeter and lead author on the study. “Human societies are hugely complex, and factors such as culture and access to healthcare make it hard to study the impact of a single factor like social relationships on survival.” The study was published on Tuesday in Proceedings of the Royal Society B.
Rhesus Macaques - Laurent Brent

Rhesus monkey family on Cayo Santiago (Puerto Rico). Source: Lauren Brent.

  • Breakthrough findings in bone marrow transplants, melanoma and anemia thanks to zebrafish. Zebrafish are important models for studying human disease. Dr. Leonard Zon, a researcher at Harvard University, is studying blood diseases and cancer. The embryos are transparent so that organ development can be visualized as it happens. Another advantage is that the mothers have many eggs allowing the study of the genetics of blood diseases and cancer that are passed on within families. This provides the ability to find similar genes in humans that cause those diseases. His work has led to two drugs now treating patients. One increases stem cells to help bone marrow transplant patients and the other treats patients with metastatic melanoma. A third drug is now in clinical trials with hopes to help people with a very rare type of anemia.
  • A new link in the gut-brain axis has been identified. A study in mice found that bacteria in the gut are implicated in cerebral cavernous malformations (CCMs), brain defects that occur in as many as one in 100 people. These malformations are blood-filled bubbles that protrude from veins in the brain and can leak or burst at any time. The researchers discovered that Gram-negative bacteria, which are typically found in the gut, accelerate CCM formation, particularly in animals that increase the expression of a certain gene, toll-like receptor 4 (or TLR4). A single course of antibiotics permanently altered CCM susceptibility in mice. This research identified unexpected roles for the microbiome, and is among the first to provide convincing evidence that these bacteria may initiate diseases in seemingly unrelated organs. The study was published on Wednesday in Nature.

Mice in a Cage

  • After decades of research, lab-grown blood stem cells have been produced providing  “hope to people with leukaemia and other blood disorders who need bone-marrow transplants but can’t find a compatible donor.” Using standard methods, these researchers transformed cells into induced iPS cells. They next inserted seven transcription factors  into the genome of of the iPS cells. Injecting these modified human cells into mice. Twelve weeks later these cells had transformed into “progenitor cells capable of making the range of cells found in human blood, including immune cells.” This research was published in the journal Nature.
  • A new gene therapy method for bone regeneration has been developed to serve as an alternative to bone grafts. Currently bone graft technology leaves many patients with fracture nonunions; where fractures are repaired but fail to fully heal. Furthermore, patients are often lead to long-term hospitalization and repeated surgeries. However, a promising gene therapy solution has been developed in mini-pigs, a clinically relevant large animal model. Researchers implanted a collagen scaffold into a critical-sized bone fracture of mini-pigs to recruit endogenous bone stem cells. Two weeks later bone morphogenetic protein-6 (BMP-6) DNA and microbubbles were injected into the fractures. This lead to bone regeneration and fracture healing over 6 weeks. This minimally invasive method shows great promise for human translation. This study was published in the Journal Science Translational Medicine
    Bone regen

    Gene therapy for bone regeneration. Source: M. Bez et al., Science Translational Medicine (2017)


Brain Awareness Week: The Role of Animals in Neuroscience

If you’re a regular reader of the Speaking of Research science blog you will know that we are very interested in neuroscience – in fact several of us are neuroscientists – so you won’t be surprised to learn that we have been following events during Brain Awareness Week (#brainweek on twitter).  Brain Awareness Week is a global campaign to increase public awareness of the progress and benefits of brain research that is organized every year by the Dana Foundation in partnership with over 100 research institutes, medical charities and universities around the world.

We thought it was a good opportunity to see what new resources on the use of animals in brain research are available from key organizations involved in Brain Awareness Week, and BrainFacts.org – a public information initiative whose launch we reported last May – delivered the goods. Brainfacts.org have been busy since we last reviewed their website, and their pages on animal research in neuroscience have grown into an excellent resource that covers a wide variety of topics including how animal research is planned, undertaken and regulated, and case studies of where animal research has made key contributions to advancing neuroscience.  Among the resources are articles written by neuroscientists and excellent videos.

The contribution of animal research to brain research has been highlighted by several recent media reports of important advances in brain science. These have ranged from a study in mice that demonstrated that high salt intake can increase the activity of a class or immune cells known as Th17 cells that have been implicated  in the early development autoimmune disorders such as Multiple Sclerosis, to a study that showed how brain implants could enable rats to sense infra red light with great potential for the development of sensory prosthetics to complement recent advances on the control of robotic limbs, to the identification in rats of a protein that plays a key role in enabling some brain cells to survive following a stroke and may lead to new therapies.

Today there was another great piece of research (1) to report as a team of stem cell researchers at UW Madison led by Professor Su-Chun Zhang  and Professor Marina Emborg chalked up another first, demonstrating for the first time that it is possible to transplant neurons generated using iPS cell techniques from a monkey’s own skin cells into their brain, where they develop into several types of mature brain cell.

GFR labelled neuron. Image courtesy of Yan Liu and Su-Chun Zhang, Waisman Center

GFR labelled neuron. Image courtesy of Yan Liu and Su-Chun Zhang, Waisman Center

The success of this study is enormously promising for the future of personalized stem cell therapies for Parkinson’s disease, stroke and other brain disorders, as the report in the University of Wisconsin Madison News makes clear.

Because the cells were derived from adult cells in each monkey’s skin, the experiment is a proof-of-principle for the concept of personalized medicine, where treatments are designed for each individual.

This neuron, created in the Su-Chun Zhang lab at the University of Wisconsin–Madison, makes dopamine, a neurotransmitter involved in normal movement. The cell originated in an induced pluripotent stem cell, which derive from adult tissues. Similar neurons survived and integrated normally after transplant into monkey brains—as a proof of principle that personalized medicine may one day treat Parkinson’s disease.

And since the skin cells were not “foreign” tissue, there were no signs of immune rejection — potentially a major problem with cell transplants. “When you look at the brain, you cannot tell that it is a graft,” says senior author Su-Chun Zhang, a professor of neuroscience at the University of Wisconsin-Madison. “Structurally the host brain looks like a normal brain; the graft can only be seen under the fluorescent microscope.”

Rhesus macaques play a key role in brain research...

Rhesus macaques play a key role in brain research…

It’s interesting to note that the development of green fluorescent protein (GFP) labelling that played a crucial role in allowing Profs. Zhang and Emborg’s team to distinguish transplanted cells from host cells in the monkey brain was made possible by research in the nematode worm Caenorhabditis elegans , a tiny worm that itself plays a perhaps surprisingly important role neuroscience.

...as do nematode worms!

…as do nematode worms!

These discoveries and advances impact on many areas of brain research, and have the potential to benefit those suffering from a wide variety of brain diseases and injuries, so it is fitting that in Brain Awareness week we salute the researchers whose ingenuity and hard work makes them possible.

Speaking of Research

1) Marina E. Emborg, Yan Liu, Jiajie Xi, Xiaoqing Zhang, Yingnan Yin, Jianfeng Lu, Valerie Joers, Christine Swanson, James E. Holden, Su-Chun Zhang “Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain” Cell Reports, Published online 14 March 2013, DOI: 10.1016/j.celrep.2013.02.016

Cancer Stem Cells: Mouse studies lead to paradigm shift in cancer research

For the past 15 years one of the most intriguing ideas in cancer research has been that the growth and spread of most – if not all – cancers is driven by cancer stem cells. The hypothesis is that only a tiny proportion of cancer cells, cancer stem cells, have the stem cell-like ability to proliferate indefinitely to produce cells that can differentiate into other cancer cell types. It suggests that the reason why cancer often returns after apparently being eradicated is that while the therapy (surgery/radiation/chemotherapy) may remove the differentiated cancer cells it fails to remove all the cancer stem cells, whose subsequent proliferation results in the cancer’s return.

Multicolored intestine tissue in genetically modified mice allows scientists to track which cells give rise to tumors.
Credit: A. G. Schepers et al., Science (2012) DOI: 10.1126/science.1224676

Today 3 teams of scientists have announced important results that provide the strongest evidence to date that cancer stem cells are indeed at the heart of cancer proliferation.

The first evidence that only a small minority of cancer cells may have the ability to proliferate indefinitely came from a study of leukemia cells in 1997, when Dr Dominique Bonnet and Dr John Dick, then both working at the University of Toronto, observed that when they injected a variety of acute myeloid leukemia (AML) cell populations obtained from human biopsy into immunodeficient mice and analyzed which cells gave rise to leukemia cells in the mice, and found that regardless of the characteristics of injected AML cells the cells that initiated the leukemic cell populations in the mice always expressed the cell surface marker CD34 and lacked the cell surface marker CD38, a key characteristic of stem cells.

Since then similar observations have been made for a wide variety of cancer types, and scientists have discovered important new facts about cancer stem cells, for example in 2009 we discussed how scientists at Stanford University had used genetic modification of bone marrow stem cells to show that leukemia stem cells were very similar to embryonic stem cells.  However, these studies all involved the transplantation of cancer cells into mice, and there has always been some concern that the manipulation of these cells during their isolation from humans and sorting into specific populations before injection into mice may have affected their behavior.

Today, three independent studies of mouse models of brain, skin and intestinal tumours, led respectively by Dr Luis Parada at the University of Texas Southwestern Medical Center, Dr Benjamin Simmons of the Gurdon Institute and Dr Cédric Blanpain of the Free University of Brussels, and Dr Hans Clevers of the Hubrecht Institute, and published in the prestigious scientific journals Nature and Science,  provide the first evidence that cancer stem cells do arise during tumour formation in intact organs, and drive tumour formation.

What these studies all share is that they were able to do this because rather than injecting cancer cells into the mice they used genetically modified mice in which cancer develops spontaneously. Using additional genetic modification to label certain types of cells they were able to track the different cell types involved in the growth and spread of cancer, and even assess the differing effects of standard cancer therapies and therapies that included drugs that specifically target cancer stem cells.

There is an excellent discussion of the three projects and their implications for cancer research in Nature News, and Science Now also offers a informative prespective on the work.  From its very first paragraphthe Nature News article highlights how these studies provide crucial information that could not be obtained through other methods:

Cancer researchers can sequence tumour cells’ genomes, scan them for strange gene activity, profile their contents for telltale proteins and study their growth in laboratory dishes. What they have not been able to do is track errant cells doing what is more relevant to patients: forming tumours. Now three groups studying tumours in mice have done exactly that. Their results support the ideas that a small subset of cells drives tumour growth and that curing cancer may require those cells to be eliminated.”

Commenting in an article in the LA Times, Dr. Owen Witte of the UCLA Broad Stem Cell Center was clear about what these results mean for cancer research.

People can stop arguing…Now they can say, ‘OK, the cells are here. We now need to know how to treat them.’ ”

And “how to treat them” will not be an easy problem to solve, perhaps drugs that target the cancer stem cells or prevent their development may be the answer, but as the Nature News, Science Now and LA Times articles stress we don’t yet know enough about the origins of cancer stem cells to be sure which approach will work.

What is true is that thanks to advanced animal research methods a huge gap in our knowledge of how cancer develops and spreads – a gap that we only recently realised existed – has been filled. As research accelerates to turn this new knowledge into effective cancer therapies we can be certain of one thing; animal research will continue to provide key insights that turn hypothesis into cures.

Paul Browne

How nerve cells reach their niche.

Developmental biology, the study of the processes through which organisms grow and develop, is an area of biomedical research where modal organisms – ranging from the slime mold Dictyostelium  discoideum to the chicken – play a crucial role, and one that has been honoured with several  Nobel Prizes in recent years.  For example, the 1995 prize for “discoveries concerning the genetic control of early embryonic development” was awarded for studies of the fruit fly  Drosophila melanogaster , and the  2002 prize for “discoveries concerning ‘genetic regulation of organ development and programmed cell death”, was awarded for research undertaken with the nematode worm Caenorhabditis elegans, while the 2007 prize for  “discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”” depended on studies of stem cells in the developing mouse embryo undertaken by Martin Evans.

Today on the Neurophilosophy blog Mo Costandi has another great example of how our knowledge of developmental biology is being advanced through animal research. In a post entitled “Astrocytes build blood vessel scaffolds for long distance neuron migrations” he discusses how a research team led by Dr Armen Saghatelyan  used  Green Fluorescent Protein labeling and genetic modification to track the processes that control the migration of nerve cells to their correct location in the developing mouse brain.

It’s fascinating work, and you can read about it on the Neurophilosophy blog here.

 

 

So what does this basic research in developmental biology mean to medicine?

Scientists have known for some time that the brain has a limited ability to repair itself following injury, for example after a stroke, and more recent studies have identified a critical role for adult neuronal precursor cells in this recovery.  But the process by these adult neuronal precursor cells migrate to the site of injury and integrate into the damaged brain circuitry is very inefficient, with only a small number of cells reaching the correct location, so scientists are working on a variety of approaches to boost the brain’s ability to repair itself.

One approach to doing this is the use of exogenous stem cells, such as the human embryonic stem cell derived neuronal precursor cells developed by the UK-based company ReNeuron that entered clinical trials for stroke in 2011.

Another avenue being pursued by several research groups around the world is to improve the efficiency with which the endogenous neuronal precursor cells migrate to and repair damaged regions of the brain. In order to develop therapies that improve endogenous brain repair scientists first need to understand the processes that drive – and limit – neuronal precursor production, migration and integration in the developing and adult brain, so that they can modify and enhance those processes to safely  optimize repair.  The work of Dr Saghatelyan and his colleagues has provided medical science with another important piece of a puzzle that when solved will benefit many thousands of stroke victims around the world.

Paul Browne

Laying the foundations of medical research

For the past couple of weeks a debate has been raging on the Opposing Views website between Speaking of Research’s Dario Ringach and the anti-vivisectionist Ray Greek. It has been a debate shaped by Dr. Greek’s attempts to persuade readers to agree with his very narrow concept of what prediction means in biology and his frankly impoverished view on the role of basic research in advancing medical science, and to oblige those debating them to accept a playing field rigged to set them at a disadvantage.  Judging by Dario’s most recent opinion piece and an article written a couple of days ago on the role of basic research Dr. Greek failed in this attempt.

British biochemist Sir Tim Hunt, who won the Nobel Prize for medicine in 2001.

Among all the discussion was one comment that directed readers to an excellent example of the value of basic research and the how study of animal models made many key discoveries possible. Earlier this week the BBC aired a program in their Beautiful Minds series featuring Sir Tim Hunt, who was awarded the Nobel Prize in 2001 for his research on how the cell cycle – through which cells grow and divide – is controlled.  Sir Tim’s work focused on the role of a family of proteins known as cyclins and as the Beautiful Minds program explains the initial breakthrough came from studies of the fluctuations in the pattern of protein expression during the cell cycle in sea urchin eggs.  This discovery was followed swiftly by the demonstration that cyclins were also present in yeast, clams and frogs, allowing Sir Tim and his colleagues to predict that they would have a role in regulating the cell cycle in many species,  including humans, a prediction that was soon confirmed to be true (1).

This program is a reminder that while discussion of animal research tends to focus on animals such as mice, rats and monkeys a lot is being learned about the fundamentals of our physiology through research on more humble model organisms, a diverse collection that includes not just sea urchins and clams but also nematode worms and flies .  These animals, along with other model organisms such as yeast and bacteria, enable us to study how living things work at a very fundamental level, laying the theoretical foundations for future applied and translational research that yields innovative treatments for disease and injury. At the same time, researchers studying other aspects of physiology often require higher mammals. The study of complex brain functions, including vision, hearing, memory, attention and motor planning, as well as how these functions fail in diseases of the central nervous system, is a prime example of this.

If you haven’t watched the Beautiful Minds series yet I strongly urge you to do so, the programs provide a fascinating (if not always flattering) insight into how science works.  And don’t delay: they are only available to view on the BBC iPlayer for another 7 days!

Paul Browne

1)      Pines J.  and Hunter T. “Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.” Cell Volume 58(5), Pages 833-846 (1989)  PubMed: 2570636

Understanding migraines: The blind leading the…err…rats

Chances are that you have either suffered from migraine yourself or have a family member or close friend who have, after all about 1 in 8 of us will suffer from migraine at some stage in our lifetime, and some sufferers experience repeated debilitating episodes over many years . While headache on one side of the brain is typical other symptoms such as nausea are very common, indeed in some migraine victims nausea is the primary symptom of the disorder.  Through a combination of studies in animals and clinical research using techniques such as fMRI and PET scans scientists have learned a lot in recent years about what happens before and during migraine episodes but we do not yet fully understand what ultimately causes the attacks, and debate rages over the relative importance of some mechanisms originating deep in brain regions such as the hypothalamus and others that start in membranes that surround the brain, (1,2).  Current treatments can help prevent migraine, reduce suffering and hasten recovery they do not work for all patients, and a better understanding of what exactly is happening before and during a migraine attack will aid the development of really effective treatments and preventative measures.  A study published in Nature Neuroscience combines clinical research with studies of rats to provide clues about a key characteristic of migraines that has until now remained unexplained, the exacerbation of the pain experienced by sufferers by light (3).

The team, lead by Rami Burnstein of Beth Israel Deaconess Medical Centre in Boston, decided to concentrate of the role of a particular subset of nerve cells in the retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) which they knew from previous mouse research to be involved in eye functions that are not image forming, such as setting the biological clock to the day night cycle.  The ipRGCs are stimulated by light both indirectly via the rods and cones and directly through a pigment called melanopsin that they themselves contain.  In order to discover if the ipRCGs are important to light sensitivity in migraine they performed a very neat clinical study involving 20 blind patients who also suffered from migraine. Six of these patients lacked any light perception due to removal of their eyes or damage to the optic nerve, while in the remaining 14 the damage to the eyes was less total, affecting the rods and cones but not ipRGCs, so that while they were unable to see images they could detect light. The results were clear, blue and grey light made the headaches of those who retained light sensitivity worse, while having no effect on the six blind individuals who lacked light perception.

Determining that the ipRGCs are involved in the exacerbation of migraine headaches by light is of course only part of the story, and Professor Burnstein’s team next turned to tracing the nerve pathways that are responsible for the increased pain, knowledge that might help to develop new treatments.  This they could not do in human subjects because the available imaging techniques do not have the precision to determine the connections between individual neurons.  In a series of studies they injected labels including Green Fluorescent Protein into particular areas of the eyes and brain, and in some cases even individual nerve cells, of anesthetized rats with and followed the path of the neurons.  They were also able to use tiny electrodes to record the effect of light on the firing of individual nerves in the brain, something that cannot yet be done in human subjects. An exciting observation was that the ipRCGs connected to cells in a region of the brain known as the posterior thalamus, itself part of the trigeminovascular pathway that is strongly implicated in migraine headache through transmission of nerve signals from the irritated outer brain membranes to the deep brain. When they examined the electrical activity of these cells they discovered that the majority of the cells within the posterior thalamus that are involved in mediating migraine pain are also light sensitive.  Finally they demonstrated that the light-sensitive pain-mediating neurons of the posterior hypothalamus connect to nerve cells in several regions of the somatosensory region of the cortex, an intriguing discovery since abnormalities in this region have previously been seen in migraine patients. This discovery is likely to encourage scientists to study the role of the somatosensory cortex in migraine in more detail.

So how important is this study? Well it’s unlikely that this discovery will lead to any treatment breakthrough in the immediate future, though the discovery that grey light can exacerbate migraine headache is new and may help patients to avoid it.  Despite a perhaps natural tendency for the news media to look for “breakthroughs” the majority of scientific papers published are like this one, providing valuable new insights into biology that contribute to our overall understanding of how biological systems work and happens when they go awry but not indicating an easy fix.  I’ve no doubt that this and many similar basic science studies will contribute to better treatments for migraine in the future, but perhaps not tomorrow!

Regards

Paul Browne

1)      Olesen J. et al “Origin of pain in migraine:evidence for peripheral sensitization” The Lancet Neurology Volume 8, Issue 7, Pages 679-690 (2009) doi:10.1016/S1474-4422(09)70090-0

2)      Alstadhaug K.B.  “Migraine and the hypothalamus” Cephalalgia Volume 29, Issue 8, Pages 809-817 doi: 10.1111/j.1468-2982.2008.01814.x

3)      Noseda R. et al. “A neural mechanism for exacerbation of headache by light” Nature neuroscience Advance Publication Online 10 January 2010 doi: 10.1038/nn.2475

Breakthrough of the Year (almost!)

As the year draws to a close it’s time to reflect on an exciting year of animal research, and there seems no better place to start than with the top 10 breakthroughs of the year as selected by the prestigious scientific journal Science. Science is of course a general science magazine, and the choices reflect this with research in diverse fields ranging from astronomy to paleontology.

Last year our sister organization in the United Kingdom reported that Science had selected cell reprogramming to produce induced pluripotent stem cells (iPS cells) as their breakthrough of the year.  Since then we have reported how the safety of iPS technology continues to improve while others have discussed exciting research which shows just how powerful the technique is by reprogramming fibroblast cells to generate healthy mice that can themselves produce offspring.

This year the top slot went to the discovery and study of Ardi, a 4.4 million year old ape who promises to shed a great deal of light on early human evolution, though it remains to be seem if she and her kind are a direct ancestor of modern humans.

We did have the consolation that one of the nine runner ups is an area of medicine to which animal research has made an enormous contribution , the return of gene therapy with Science claiming that  this year “… gene therapy turned a corner, as researchers reported success in treating several devastating diseases”. These diseases include X-Linked adrenoleukodystrophy, a usually fatal disease of the brain and nervous system, Leber’s congenital amaurosis, an inherited eye disorder that leads to blindness, and severe combinedimmunodeficiency (SCID)due to a lack of an enzyme called adenosinedeaminase.

Only last month I wrote about the crucial role of research with mice in developing the gene therapy for X-Linked adrenoleukodystrophy, while both Anna Matynia and I have written about Leber’s congenital amaurosis.  However,  we have not yet had an opportunity to discuss the therapy developed for treating SCID  in patients whose immune system has collapsed because they lack an enzyme named adenosine deaminase (ADA) which is crucial for removing toxic metabolites from cells.

A clinical trial published in January by the New England Journal of Medicine (1) reported how an Italian team had successfully treated  children with SCID by harvesting bone marrow stem cells from the boys and treating these cells with a retroviral vector containing the ADA gene that produces adenosine deaminase, and then transplanting the modified cells back into them.  In 5 of the boys the therapy restored normal function and significant improvements in the function of the immune system were observed in the other 5.  This therapy has been a couple of decades in development and one of the key investigators involved in this effort, and indeed in the recent clinical trial,  has been Dr. Claudio Bordignon of the University of Milan. Dr. Bordignon developed techniques that enabled scientists to study the ability of retrovirus transformed bone marrow cells from patients with ADA-SCID  to restore immune function in  the NOD/SCID mice that lack a functioning immune system (2).  This enabled him and his team to develop retroviral vectors that could safely drive the production of adenosine deaminase in bone marrow stem cells that survived for long periods after transplantation and are suitable for use in ADA-SCID patients where they need to function for many years.

It’s great to see an area of medical research that we’ve been following closely over the past year receive this recognition from Science, and we hope that as with iPS cells in 2009 gene therapy continues to show what it can do in 2010.

Paul Browne

1)      Aiuti A. et al.”Gene therapy for immunodeficiency due to adenosine deaminase deficiency.” N Engl J Med. Volume 360(5), Pages 447-458 (2009) DOI:10.1056/NEJMoa0805817

2)      Ferrari G. et al “An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency.” Science. Volume 251(4999), Pages 1363-1366 (1991) PubMed:1848369