Cynomolgus macaque. New research in these primates suggests that a gene delivery strategy that produces follistatin can improve muscle mass and function. (Credit: iStockphoto/Anna Yu)


ScienceDaily (Nov. 13, 2009) – A study appearing in Science Translational Medicine puts scientists one step closer to clinical trials to test a gene delivery strategy to improve muscle mass and function in patients with certain degenerative muscle disorders. 

Severe weakness of the quadriceps is a defining feature of several neuromuscular disorders. Researchers at Nationwide Children’s Hospital have shown that a gene delivery strategy that produces follistatin — a naturally occurring protein that inhibits myostatin, a growth factor expressed specifically in skeletal muscle — directly to the quadriceps of non-human primates results in long-term gene expression with muscle enhancing effects, including larger muscles with greater strength. 

Previously, Nationwide Children’s researchers demonstrated follistatin’s therapeutic potential using rodent models. This more recent study produced similar results in non-human primates, in a translational study to demonstrate efficacy in safety in a species more closely related to humans. Non-human primates that received the injection of the follistatin transgene experienced pronounced and durable increases in muscle size and strength. Muscle growth occurred for 12 weeks after treatment, after which time the growth rates appeared to stabilize and were well tolerated, with no adverse events noted over the course of the 15-month study. 

“Our studies indicate that this relatively non-invasive approach could have long-term effects, involve few risks and could potentially be effective in various types of degenerative muscle disorders including multiple forms of muscular dystrophy,” said the study’s corresponding author, Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy of The Research Institute at Nationwide Children’s Hospital. 

Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at Nationwide Children’s added, “These findings serve as the basis for testing in patients and give us confidence in moving forward with our translational program of follistatin to enhance muscle mass.” 

The research team has developed a plan with the Food and Drug Administration and is currently in the process of performing the formal toxicology and biodistribution studies to support initiating a human clinical trial. 

The potential use of this strategy for muscle strengthening has important implications for patients with muscle diseases including Duchenne muscular dystrophy — the most common form of muscular dystrophy — as well as for the planned first clinical trial for inclusion body myositis. It also may be applicable to other forms of muscular dystrophy, such as facioscapulohumeral muscular dystrophy, in which gene replacement or other types of gene manipulation are not feasible because of the absence of a specific gene defect.

In addition to their roles at Nationwide Children’s, Drs. Kaspar and Mendell hold faculty posts at The Ohio State University College of Medicine.

Journal reference:

  • 1. Kota et al. Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates. Science Translational Medicine, 2009; 1 (6): 6ra15 DOI: 10.1126/scitranslmed.3000112

Adapted from materials provided by Nationwide Children’s Hospital.

Gene Therapy Turnaround – Q & A


Mark Kay MD
Image: Stanford University


The-Scientist.com, November 16, 2009, by Victoria Stern  —  Judging by the stream of studies in the last few months, it seems the field of gene therapy is beginning to replace its troubled history with the beginnings of a promising future.

In September, researchers reported that viral delivery of a pigment gene allowed colorblind squirrel monkeys to see red and green for the first time, providing hopes that the technique could be used to treat colorblindness in humans. In October, transplant scientists showed they could bolster the health of donor lungs by supplying a gene coding for an anti-inflammatory molecule. Earlier this month came a report in which gene therapy was used to halt the progression of adrenoleukodystrophy, a fatal brain disease, in two young boys using a virus derived from HIV to deliver the gene for the missing enzyme. Finally, a study published (November 11) in Science Translational Medicine reports that administering a gene blocking muscle breakdown to monkeys boosts the size and strength of their muscles — suggesting such a treatment may one day help patients with degenerative muscle disorders.

With the flurry of recent successes, Mark Kay, director of the Human Gene Therapy program at Stanford University School of Medicine and one of the founders of the American Society of Gene and Cell Therapy, believes that “the mood in the field is pretty positive.” Kay took time to chat with The Scientist about the progress that’s been made in the field the hurdles still left to overcome.

The Scientist: Can you start by describing the outlook for gene therapy after these recent successes?

Mark Kay: These studies have provided a great model for the potential success of gene therapeutics. There is a lot of optimism in the gene therapy field right now that these therapies will work well. In the course of gene therapy research, there have been a lot of unanticipated hurdles, but in a relatively short time [since trials began in the 1980s], I think we have made a lot of progress.

TS: What kinds of conditions are best suited for gene therapy?

MK: There are a lot of conditions for which gene therapy could work. The easiest target appears to be single gene disorders, including adrenoleukodystrophy and blindness, where only a small percentage of cells need to be fixed.

Other disorders caused by a single gene are more complicated to treat, however. For instance, Duchene muscular dystrophy, which affects all the skeletal and cardiac muscle, requires correcting one gene, but the defect needs to be changed in a large number of cells to make a clinical treatment successful. Cancers, which deal with many different cells in the body, will also be difficult to cure with gene therapy, but perhaps when used in combination with other treatments, gene therapy may turn out to have therapeutic results.

TS: What do you see as the main technical hurdles that gene therapeutics has yet to overcome?

MK: I would lay out four main hurdles that we have to overcome:

1) First, it’s essential to get a vector to the specific cells in high enough levels to produce the desired response but not have toxicity problems.

2) Once the vector with the encoded gene reaches the desired cell, it must be internalized and get to the nucleus. The cell has naturally implemented a lot of barriers to prevent this new DNA from interacting with the existing DNA, but viruses are good delivery tools because they have developed mechanisms to get passed these hurdles. Overcoming this difficulty has turned out to be more difficult than previously anticipated.

3) Once in nucleus, the new gene must be able to persist for the desired amount of time. The cell can sometimes shut the new gene off, making it ineffective.

4) The final main problem is the potential for an immune response. If the gene product is recognized as a foreign agent, the body can mount an attack against the vector or the protein.

Another general issue is determining how long the gene therapy should persist. If you’re treating an infection or cancer, you only need gene therapy to last until the infection or cancer has been eliminated. But in genetic disorders, you need lifelong gene correction.

TS: Are there still safety concerns?

MK: People are always going to be cautious moving forward. We don’t know for sure what the risks of some of these treatments might be. For instance, there is increasing evidence that the patients who developed leukemia [two children whose X-linked Severe Combined Immunodeficiency Disease was cured with gene therapy in the highly publicized 1998 trial later developed leukemia] may have a very disease-specific type of problem. Any time you’re inserting new DNA into cells there will always be some risk that it will increase the chances of developing a malignancy. There are many medical treatments unrelated to gene therapy where the risk of developing cancer is reasonably high. For example, by treating one type of cancer, you may be using molecules that increase your risk of developing another type of cancer. As we continue to move into unknown territory in gene therapy, it will be important to watch for toxicity and longer-term side effects.

TS: What ethical issues remain that the field will still have to address?

MK: The bigger ethical dilemmas will likely come in the future when we have to decide where to draw the line in terms of what conditions we’re willing to treat. Clearly gene therapy should be used to combat severe mental disorders or genetic diseases, but deciding whether to treat neurobehavioral disorders, such as depression or addiction, provides more of a gray area. And should we use gene therapy to enhance or select for certain traits, like higher IQ or athletic ability. Even though it’s not possible to treat any of these disorders now, with more advances in gene therapy, people may start asking these questions in the future.

TS: What’s the next frontier in the gene therapy?

MK: While most of gene therapy is focused on adding another copy of a functional gene, another path may be to design molecules that can turn off defective genes. For instance, in Huntington’s disease, gene therapy could be used to turn off the defective gene that produces an abnormal protein.

I think one of the most important aspects for a lot of these diseases is to treat them early on, before the pathology has caused irreversible damage. Prevention is much more effective because it’s much harder to fix a problem in a neurodegenerative disease or muscular dystrophy when the damage has already been done.

By Matthew Herper
Forbes Magazine dated November 30, 2009


Each of these seven has had a seminal, and sustained, impact on the fields of medicine and biomedical research. They are busy gearing up for the next global pandemic, building momentum for scientific research and ushering in a new era of personalized medicine.

Zerhouni was the director of the National Institutes of Health from 2002 to 2008. He is currently a professor of radiology and biomedical engineering at Johns Hopkins University.


1    Dr. Francis S. Collins, Director, National Institutes of Health (NIH)
A renowned geneticist, Collins runs the world’s largest biomedical research agency

2    Dr. Anthony S. Fauci, Director, National Institute of Allergy & Infectious Diseases
Fauci’s influence will only expand as infectious diseases pose a greater threat worldwide

3    Dr. Chen Zhu, Minister of Health, People’s Republic of China
Leading China’s remarkable progress in pandemic preparedness and health policy

4    Dr. David L. Baltimore, Chairman, American Association for the Advancement of Science
Baltimore is influential in all big research areas: HIV/AIDS, global health and stem cells

5    Dr. Harold E. Varmus, President, Memorial Sloan-Kettering Cancer Center
Varmus has Obama’s ear on the President’s Council of Advisors on Science & Technology

6    Dr. Tadataka Yamada and William Gates III
President, Global Health Program, and founder, Bill and Melinda Gates Foundation
This power duo is changing global health from an afterthought to the issue du jour

7    Drs. James Thomson and Shinya Yamanaka University of Wisconsin School of Medicine and Kyoto University
Their method for creating stem cells without using embryos will change medicine

By Gabe Mirkin MD, November 16, 2009  —  There are two absorption systems in your body. Food that is easily broken down is absorbed into your upper intestinal tract. If you cannot absorb a particular food, it goes to the lower intestinal tract (colon), where bacteria in your colon ferment it to smaller products that can be absorbed.

Your colon is loaded with good and bad bacteria. Bad bacteria such as clostridia that are kept in check by good bacteria. If you take an antibiotic that knocks off the good bacteria, the clostridia can overgrow and cause diarrhea.

The good bacteria break down soluble fiber to form chemicals such as short chain fatty acids that are absorbed into your bloodstream and travel to your liver where they block the liver from making cholesterol and help to prevent heart attacks. These short chain fatty acids also reduce inflammation, so they help to control the bloody diarrhea and ulcers caused by Crohn’s disease. They also reduce swelling and pain of arthritis, diabetes and psoriasis, and some studies show they may even improve your immunity to help you to kill germs.

If you wish to encourage the growth of good bacteria in your colon, you have two choices: probiotics or prebiotics. Probiotics are living microorganisms, the good bacteria, that live in the colon and reduce inflammation and help prevent and treat Crohn’s disease, psoriasis, arthritis, and perhaps even certain types of cancers. Prebiotics are nondigestible food ingredients that cannot be absorbed in the upper intestinal tract and travel to the colon where they serve as a medium to encourage the growth of the good bacteria.

Live-culture yogurt is a readily available source of good bacteria. However, the lactobacilli that are in live cultures of yogurt will not colonize in your intestines, so they disappear if you stop eating yogurt every day. Most yogurt products do not contain live cultures; read the labels carefully.

One strain of good bacteria that has been studied extensively and has been shown in controlled scientific studies to have the ability to colonize in the intestines is called lactobacillus GG. It was isolated from intestines of humans by two professors at Tufts Medical School named Sheldon Gorbash and his colleague named Golden, hence the name lactobacillus GG. They have patented their product and make a lot of money from it.

Several studies show that Lactobacillus GG can help control the frequency and severity of infectious diarrhea in children. Diarrhea that is often caused by taking antibiotics can be prevented by taking either Lactobacillus GG or Saccharomyces boulardii with the antibiotics. A probiotic preparation (VSL=3 – 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has been shown to maintain remission in ulcerative colitis as well as in preventing the postoperative recurrence of Crohn’s disease. Taking probiotic compounds is well tolerated and safe.

Prebiotics are found in certain foods that are not completely absorbed in your upper intestinal tract pass to your colon and form the food that encourages growth of the good bacteria. Soluble fiber is the part of these foods that is most likely to encourage the growth of good bacteria. Prebiotic supplements are available, but it is easier and cheaper just to eat plenty of the foods that provide this benefit. Good sources of soluble fiber are whole grains, beans, seeds, vegetables and nuts.

The use of probiotics in gastrointestinal disease. Canadian Journal of Gastroenterology, 2001, Vol 15, Iss 12, pp 817-822. KL Madsen. Univ Alberta, 536 Newton Bldg, Edmonton, AB T6G 2C2, CANADA

Updated 8/22/09


An artists’s impression of the LCROSS rocket that NASA intentionally crashed into the Cabeus crater near the Moon’s south pole Photo: AP/NASA


Lunar colonists may one day enjoy a view of Earth similar to the one scene in this famous photo, “Earthrise,” taken on Dec. 24, 1968, during the Apollo 8 mission.


A new chapter in space exploration has been opened up after Nasa confirmed that their mission to bomb the Moon had found “significant quantities” of frozen water

Finding could mean drinking water, rocket fuel, more for future lunar camps 

GoogleNews.com, msnbc.msn.com, November 13, 2009,  by Jeanna Bryner  —  Scientists said the “exciting” findings had gone “beyond expectations” as fully formed ice was found in a crater on the moon.

They said that the ice – thought to be in granules mixed with grains of Moon dust – heralded a major leap forward in space exploration and boosted hopes of a permanent lunar base.

The water was found in one mile high plume of debris that was kicked up by the Lunar Crater Observation and Sensing Satellite (LCROSS) last month when it crashed into the Cabeus crater near the Moon’s south pole.

“We are ecstatic,” said Anthony Colaprete, project scientist and principal investigator for the $50 million space mission.

“Indeed, yes, we found water. And we didn’t find just a little bit, we found a significant amount.”

Hopes, dreams and practical plans to colonize or otherwise exploit the moon as a source of minerals or a launch pad to the cosmos got a boost today with NASA’s announcement of significant water ice at the lunar south pole.

The LCROSS probe discovered the equivalent of a dozen 2-gallon buckets of water in the form of ice, in a crater at the lunar south pole. Scientists figure there’s more where that came from.

“The presence of significant quantities of ice on the lunar surface catapults the moon from an interesting waypoint to a critical launching pad for humanity’s exploration of the cosmos,” said Peter Diamandis, CEO and chairman of the X Prize Foundation, which is running a $30 million contest for private moon rovers. “We’re entering a new era of lunar exploration – ‘Moon 2.0,’ in which an international group of companies and governments will use the ice and other unique resources of the moon to help us expand the sphere of human influence, and to help us monitor and protect the Earth.”

The water discovery firms up previous detections of the signature of water molecules by three independent spacecraft. But the new finding makes more of a splash in that the detections come from both infrared and ultraviolet measurements, and a lot more of it was detected than scientists had expected.

“It is a big ‘wow,'” said Jack Burns of the Center for Astrophysics and Space Astronomy at the University of Colorado, Boulder, and director of the Lunar University Network for Astrophysics Research.

Set up lunar camp
Having that store of water on the moon could be a boon to possible future lunar camps. In addition to a source of drinking water, lunar water ice could be broken into its constituent hydrogen and oxygen atoms, ultimately to be used in rocket fuel. That would mean spacecraft ferrying future colonists to the moon would not have to take fuel for the return trip, or the fuel could be used to launch trips beyond the moon. And water could be used as a shield from cosmic radiation.

“We now can say … that the possibility of living off the land has just gone up a notch,” said Peter Schultz, professor of geological sciences at Brown University and a co-investigator on the LCROSS mission, referring to past detections of water on the moon.

The new discovery comes just as the Obama administration is deciding whether to continue on with NASA’s goal of putting astronauts back on the moon by 2020. Today’s news could tip the scales toward another lunar leap.

“It’s going to boost the interest in the moon, no doubt about it,” said with Michael Wargo, chief lunar scientist for Exploration Systems at NASA Headquarters. “It’s going to provide additional information that will inform the decision that will inform the future of human space exploration.” He added that the new finding will likely be taken into account when that administrative decision is made.

“In terms of the clearly most practical destination for the next two to three decades for human exploration it has to be the moon,” Burns told SPACE.com.

Big challenges ahead
In the midst of floating on “Cloud 9,” as Burns described his reaction to the water discovery, are the logistics of actually setting up a lunar colony.

“The devil is in the details,” Wargo said, adding, “None of our spacesuits that we currently have would be appropriate for that extreme an environment.”

Any materials built for Earth-like temperatures won’t work on the moon. “They don’t bend anymore, they fracture, and they fracture brittle-y, and so everything gets extremely brittle at those temperatures,” Wargo said.

NASA scientists have been quietly working in their tool shops on innovative ways of mining and using the goods.

The water could also be pumped into the roof of a lunar habitat to shield astronauts from cosmic radiation. “So think of it as a layer of insulation like you would have in the roof of your house,” Burns said. “Instead of thermal insulation this is insulation from radiation from the sun.”

New page in lunar history
When Apollo astronauts visited the moon 40 years ago, the picture was of a bone-dry rock. That picture has only changed within the last couple of decades as scientists began to suspect that the moon’s polar regions could hold stores of water ice in so-called cold traps that are permanently in the darkness and can reach just tens of degrees above absolute zero, Burns said.

The LCROSS probe impacted one such cold trap, a crater called Cabeus, on Oct. 9. The $79 million spacecraft, preceded by its Centaur rocket stage, hit the lunar surface in an effort to create a debris plume that could be analyzed by scientists for signs of water ice.

This watery find may just be the first big one with more to come. “This was a random shot in an area of permanent darkness and there may be many more places that could have more of this stuff,” Schultz told SPACE.com. “This is like opening Pandora’s Box.”

“It’s been unfortunate that some have said, ‘Moon, been there done that,'” Burns said. “We only went to the moon six times and we didn’t go to the most interesting places on the moon. There’s so much more to discover about the moon just from a scientific perspective, what it can tell us about the formation of the Earth.”

Space.com senior writer Andrea Thompson contributed to this report.