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Researcher hunts for sickle cell anemia cure with gene targeting, stem cells

Posted: June 30, 2012 at 4:13 am

Halfway around the world in India, Sivaprakash Ramalingam had heard of Johns Hopkins researchers using a promising new technique for gene therapy that he hoped to integrate with stem cells to cure diseases.

After getting a doctorate in biochemistry in his native country, he came to Baltimore four years ago to study under the technique's pioneer, Srinivasan Chandrasegaran, at Hopkins' Bloomberg School of Public Health. Ramalingam's research has led him down the path of seeking a cure for sickle cell anemia, a painful, life-shortening blood disorder that afflicts many in his home region in southern India. In the United States, the disease affects 70,000-100,000 people, mostly African-Americans, according to the National Heart Lung and Blood Institute.

"I couldn't have done this type of research in India," said Ramalingam. "I wanted to use this technique with stem cells to treat disease."

Ramalingam's research was given a lift last month by the state. He was one of 17 researchers who was funded by the Maryland Stem Cell Research Commission, a state entity that has doled out roughly $10 million to $12 million a year in taxpayer funds since its founding in 2006.

The program helps keep Maryland competitive in stem cell research when other states have instituted similar ones to lure scientists and biotechnology companies. More than 100 researchers applied for funding from the program, many from Johns Hopkins and the University of Maryland.

"There's definitely a great demand for the awards," said Dan Gincel, the commission's director. "We're trying to figure out how to fund so many researchers."

Gincel said Ramalingam's work is interesting because his approach could have applications beyond sickle cell anemia. It could be used to treat other diseases and, for instance, modify plants and crops to make them resistant to pests.

Ramalingam received a $110,000 award two years ago from the commission to help fund his post-doctoral fellowship; the commission invested more money in his work this year because he was continuing to progress with it, Gincel said.

"The approach can be translated to many other diseases, which is what we want to see with stem cells," said Gincel.

Ramalingam is applying a relatively new technique called zinc finger nuclease, or ZFN, to try to cure sickle cell anemia. With ZFN, Ramalingam is able to target and replace specific, problem-causing sequences of the human genome with healthier genetic material.

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Former Auburn coach getting stem cell treatments for Lou Gehrig’s disease

Posted: June 30, 2012 at 4:13 am

MOBILE, Alabama -- The Baldwin County doctor that treated former Alabama football players with adult stem cells also has treated at least two people diagnosed with amyotrophic lateral sclerosis, also known as Lou Gehrigs disease.

One of the ALS patients, former NFL football player and college coach Frank Orgel, recently underwent a new stem cell reprogramming technique performed by Dr. Jason R. Williams at Precision StemCell in Gulf Shores.

Before the injections, Orgels health had declined. He could not move his left arm or leg. He couldnt walk or stand on his own, he said.

Within a few days of having the stem cell treatment, Orgels constant muscle twitching diminished, said Bob Hubbard, director of stem cell therapy at the practice. Within weeks, he was able to walk in a pool of water and stand unassisted.

I think its helped me, said Orgel, who was a defensive coordinator at Auburn under former head coach Pat Dye. Im walking in the pool and I used to drag my feet. Now my left leg is picking up.

ALS is a progressive neuro-degenerative disease that affects nerve cells in the brain and the spinal cord. The progressive degeneration of the motor neurons in ALS eventually leads to death, according to the ALS Association.

Stem cells, sometimes called the bodys master cells, are precursor cells that develop into blood, bones and organs, according to the U.S. Food and Drug Administration, which regulates their use. Their promise in medicine, according to many scientists and doctors, is that the cells have the potential to help and regenerate other cells.

While Williams treatments are considered investigational, he has said, they meet FDA guidelines because the stem cells are collected from a patients fat tissue and administered back to that patient during the same procedure.

Orgel, 74, said Williams told him it would take between eight months to a year for his nerves to regrow. He is traveling to Gulf Shores from his home in Albany, Ga., this weekend for another stem cell treatment, Orgel said: I need to get to where I can walk.

In recent years, Orgel has gone to Mexico at least three times for different types of treatments, not sanctioned in the U.S. At least once, he said, he had placenta cells injected into his body. That didnt work, Orgel said. I didnt feel any better.

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Former Auburn coach getting stem cell treatments for Lou Gehrig's disease

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Turning skin cells into brain cells: Huntington’s disease in a dish

Posted: June 29, 2012 at 4:14 pm

ScienceDaily (June 28, 2012) Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating "HD in a dish," the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and -- eventually -- death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

"Having these cells will allow us to screen for therapeutics in a way we haven't been able to before in Huntington's disease," saysChristopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the study's lead researchers. "For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic."

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration.These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntington's disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimer's and Parkinson's.

To conduct their experiment, Ross took a skin biopsy from a patient with very early onset HD.When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross' team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed by the lab of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for Cell Engineering, into induced pluripotent stem cells. A second cell line was generated in an identical fashion in Dr. Ross's lab from someone without HD. Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

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Turning skin cells into brain cells: Huntington's disease in a dish

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Gazette.Net: Rockville biotech tests stem cells for depression

Posted: June 29, 2012 at 4:14 pm

Neuralstem, the Rockville company thats developing a stem cell treatment for patients with amyotrophic lateral sclerosis, has begun testing the safety of its treatment for major depressive disorder.

The compound, NSI-189, stimulates new neuron growth in the brain's hippocampus region, which scientists think is involved in depression and other conditions, including Alzheimer's disease, anxiety and post-traumatic stress disorder, according to a company statement. The phase 1b study involves 24 depressed patients and is expected to run six months.

"We believe it could help patients who suffer from depression via a new mechanism that does not seek to modulate brain chemistry, but rather stimulates new neuron growth in the hippocampus and increases hippocampal volume, thereby potentially addressing the problem at the source," Karl Johe, Neuralstem's chief scientific officer, said in the statement.

The company has researched hippocampal stem cell lines since 2000 and in 2009 won U.S. patents for four chemical entities that generate new neurons. In studies, NSI-189 stimulated such growth in mice.

In other Maryland bioscience industry news:

Supernus Pharmaceuticals has received tentative marketing approval from the Food and Drug Administration for its once-daily, extended release version of an epilepsy treatment.

The FDA said it has completed its review of Trokendi XR and no more clinical trials are required. Final approval hinges on resolving a marketing exclusivity issue that involves a specific pediatric population, according to the FDA's letter to Supernus.

Trokendi XR is an extended-release version of topimarate, which is marketed as Topamax by Janssen Pharmaceuticals of Titusville, N.J., to treat seizures and migraine headaches.

"We will continue to work closely with the FDA to further understand the outstanding issue and move forward towards final approval," CEO Jack Khattar said in the statement.

Supernus, which went public this year, also said the FDA denied a petition filed in 2011 by Upsher Smith Laboratories related to its Trokendi XR application.

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Research and Markets: Handbook of Stem Cells, Two-Volume Set. Edition No. 2

Posted: June 29, 2012 at 4:14 pm

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/4ghhzd/handbook_of_stem_c) has announced the addition of Elsevier Science and Technology's new report "Handbook of Stem Cells, Two-Volume Set. Edition No. 2" to their offering.

New discoveries in the field of stem cells increasingly dominate the news and scientific literature revealing an avalanche of new knowledge and research tools that are producing therapies for cancer, heart disease, diabetes, and a wide variety of other diseases that afflict humanity. The Handbook of Stem Cells integrates this exciting area of life science, combining in two volumes the requisites for a general understanding of adult and embryonic stem cells. Organized in two volumes entitled Pluripotent Stem Cells & Cell Biology and Adult & Fetal Stem Cells, this work contains contributions from the world's experts in stem cell research to provide a description of the tools, methods, and experimental protocols needed to study and characterize stem cells and progenitor populations as well as a the latest information of what is known about each specific organ system.

- Provides comprehensive coverage on this highly topical subject

- Contains contributions by the foremost authorities and premiere names in the field of stem cell research

- Companion website contains over 250 color figures in presentation format

For more information visit http://www.researchandmarkets.com/research/4ghhzd/handbook_of_stem_c

Source: Elsevier Science and Technology

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Ipo 8 weeks after stem cell therapy at Surf Paws Animal Hospital – Video

Posted: June 29, 2012 at 4:13 pm

28-06-2012 13:54 About 5 months ago, she came home from the beach with my husband limping on her right back leg. Now 8 weeks later after stem cell therapy... we were happy (well, maybe not so much...) to see her back to her old, wild, hyper self again.

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Medistem Receives Notice of Patent Allowance Covering Fat Stem Cell Therapy of Autoimmune Diseases

Posted: June 29, 2012 at 4:13 pm

SAN DIEGO CA--(Marketwire -06/29/12)- Medistem Inc. (MEDS) announced today notice of allowance from the United States Patent and Trademark Office (USPTO) for a patent covering the use of fat stem cells, and cells associated with fat stem cells for treatment of diseases related to a dysfunctional immune system. Such diseases include multiple sclerosis, Type 1 diabetes, rheumatoid arthritis and lupus. The allowed patent, entitled "Stem Cell Mediated Treg Activation/Expansion for Therapeutic Immune Modulation" has the earliest priority date of December 2006.

"We have previously published that giving multiple sclerosis patients cells extracted from their own fat tissue, which contains stem cells, appears to confer clinical benefit in a pilot study," said Thomas Ichim, CEO of Medistem. "The current patent that has been allowed, in the broadest interpretation of the claims, gives us exclusive rights to the use of specific types of fat stem cell therapy for autoimmune diseases such as multiple sclerosis."

Subsequent to the filing of the patent application, Medistem together with collaborators at the Lawson Health Sciences Research Institute, Canada, reported data that fat tissue contains high numbers of T regulatory cells, a type of immune cell that is capable of controlling autoimmunity.

This finding was independently confirmed by Dr. Diane Mathis' laboratory at Harvard University, who published a paper in the prestigious journal, Nature Medicine, in which detailed experimental evidence was provided supporting the initial finding that adipose tissue contains high numbers of T regulatory cells. A video describing the paper can be accessed at http://www.youtube.com/watch?v=rEJfGu29Rg8.

The current patent discloses the use of T regulatory cells from fat, combinations with stem cells, and use of fat-derived mononuclear cells. Given that there are currently several groups utilizing this technology in the USA in treating patients, Medistem believes revenue can be generated through enforcement of patent rights.

"Our corporate philosophy has been to remain highly focused on our ongoing clinical stage programs using Medistem's universal donor stem cell, the Endometrial Regenerative Cell (ERC), in the treatment of critical limb ischemia and congestive heart failure," said Dr. Vladimir Bogin, Chairman and President of Medistem. "However, due to the ease of implementation of our fat stem cell technology, combined with the major burden that autoimmune diseases have on our health care system, we are highly incentivized to explore partnering, co-development and licensing opportunities."

Autoimmune conditions occur as a result of the body's immune system "turning on itself" and attacking its own organs or cells. Current treatments for autoimmune conditions are based on "globally" suppressing the immune system by administration of immunosuppressive drugs. This is associated with an increased predisposition to infections and significant side effects. The utilization of stem cells and T regulatory cells offers the potential to selectively suppress pathological immunity while preserving the ability of the body to fight bacteria and viruses. According to the NIH there are approximately 23 million victims of autoimmune conditions.

Links to Documents:

Link to peer-reviewed publication: http://www.translational-medicine.com/content/pdf/1479-5876-7-29.pdf

Link: http://www.marketwire.com/press-release/medistem-files-patent-application-on-therapeutic-cell-population-found-in-fat-tissue-frankfurt-s2u-812298.htm

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Taking the fate of stem cells in hand: RUB researchers generate immature nerve cells

Posted: June 29, 2012 at 5:18 am

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Dr. Stefan Wiese stefan.wiese@rub.de 49-234-322-2041 Ruhr-University Bochum

RUB biologists have deliberately transformed stem cells from the spinal cord of mice into immature nerve cells. This was achieved by changing the cellular environment, known as the extracellular matrix, using the substance sodium chlorate. Via sugar side chains, the extracellular matrix determines which cell type a stem cell can generate. "Influencing precursor cells pharmacologically so that they transform into a particular type of cell can help in cell replacement therapies in future" says Prof. Dr. Stefan Wiese, head of the Molecular Cell Biology work group. "Therapies, for example, for Parkinson's, multiple sclerosis or amyotrophic lateral sclerosis could then become more efficient." The team describes its findings in Neural Development.

Sulphate determines the fate of stem cells

Sodium chlorate acts on metabolism enzymes in the cell which attach sulphate groups to proteins. If these sulphates are not installed, the cell continues to form proteins for the extracellular matrix, but with modified sugar side chains. These chains in turn send out signals that define the fate of the stem cells. Stem cells can not only develop into nerve cells, but also form astrocytes or oligodendrocytes, which are, for instance, responsible for the mineral balance of the nerve cells or which form their insulation layer. What happens to the stem cells if the sulphate pattern is changed by sodium chlorate was examined by Dr. Michael Karus and his colleagues.

Positive side effects: nerve cells remain immature

The RUB-laboratories of Prof. Dr. Stefan Wiese, Prof. Dr. Andreas Faissner and Prof. Dr. Irmgard Dietzel-Meyer collaborated for the study. Using antibodies, the researchers showed that cells which they had treated with sodium chlorate developed into nerve cells. They also analysed the flow of sodium ions into the cells. The result: treated cells showed a lower sodium current than mature nerve cells. Sodium chlorate thus favours the development of stem cells into nerve cells, but, at the same time, also inhibits the maturation - a positive side effect, as Wiese explains: "If sodium chlorate stops the nerve cells in an early developmental phase, this could enable them to integrate into the nervous system following a transplant better than mature nerve cells would do."

###

Bibliographic record

M. Karus, S. Samtleben, C. Busse, T. Tsai, I.D. Dietzel, A. Faissner, S. Wiese (2012): Normal sulphation levels regulate spinal cord neural precursor cell proliferation and differentiation, Neural Development, doi: 10.1186/1749-8104-7-20

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Disease fight: turning skin cells to neurons

Posted: June 29, 2012 at 5:18 am

Disease fight: turning skin cells to neurons June 28th, 2012, 4:04 pm posted by Pat Brennan, science, environment editor

UC Irvine professor Leslie Thompson, with human brain image behind her. Photo by Daniel A. Anderson, UC Irvine.

Using stem cells derived from skin cells, scientists including a UC Irvine team say they have created human neurons that exhibit the effects of Huntingtons disease promising the possibility of testing treatments for the deadly disorder in a petri dish.

Their discovery not only sidesteps ethical issues surrounding the use of human embryonic stem cells, but offers the chance to produce far more diseased neurons, at various stages of disease progression, than ever have been available to researchers before.

This is a relatively new technique where you can reprogram an adult cell, in this case a skin cell, back to this early stem-cell stage, and then guide those into making neurons, said Leslie Thompson, a UC Irvine professor and a senior author of a study announcing the discovery that was published online Thursday.

Huntingtons disease is an inherited, neurodegenerative disorder that is always fatal. It typically strikes in middle age, gradually robbing its victims of the ability to walk and interfering with other basic brain functions.

Huntington's disease cells on their way to becoming neurons. Image courtesy Leslie Thompson, UC Irvine.

Its like Parkinsons in that its a movement disorder in this case, involuntary movements, and rigidity, Thompson said. You know what is going on, but parts of memory are being impaired; you have an impaired ability to walk, think, talk.

Victims typically die of the diseases effects falling, or choking during pneumonia and some especially severe mutations can strike young children. The disease affects about 30,000 people in the United States, and no treatments exist even to slow the onset of symptoms.

The scientists, including UCIs Leslie Lock and Peter Donovan, director of the Sue and Bill Gross Stem Cell Research Center, as well as others from universities around the country and in Italy and Great Britain, used a variety of cell lines to reveal the genetic underpinnings of Huntingtons.

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Huntington’s disease neurons created from stem cells

Posted: June 29, 2012 at 5:18 am

An international consortium of Huntington's disease experts, including several from the Sue & Bill Gross Stem Cell Research Center at UC Irvine and the UCSF Gladstone Institutes, has generated a human model of the deadly inherited disorder directly from the skin cells of affected patients.

The re-created neurons, which live in a petri dish, will help researchers better understand what disables and kills brain cells in people with HD and let them gauge the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

UCI scientists were part of a consortium that in 1993 identified the autosomal dominant gene mutation responsible for HD, but there is still no cure, and no treatments are available to even slow its onset or progression. The research, published online today in the journal Cell Stem Cell, is the work of the Huntington's Disease iPSC Consortium. Participants examined several other cell lines and control cell lines to ensure that their results were consistent and reproducible in different labs.

"Our discovery will enable us for the first time to test therapies on human Huntington's disease neurons," said Leslie Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior, one of the world's leading HD experts and a senior author of the study. "This has been a remarkable time in HD research, with the advent of stem cell technologies that have allowed these scientific advancements. Also, having a team of scientists working together as a consortium has benefited the research tremendously and accelerated its pace."

Huntington's is such a rare disease, although it is the most common inherited neurodegenerative disorder. It afflicts approximately 30,000 people in the United States-with another 75,000 people carrying the gene that will eventually lead to it.

"An advantage of this human model is that we now have the ability to identify changes in brain cells over time-during the degeneration process and at specific stages of brain-cell development," said Gladstone Senior Investigator Dr. Steve Finkbeiner. "We hope this model will help us more readily uncover relevant factors that contribute to Huntington's disease and especially to find successful therapeutic approaches."

UC Irvine press release

Gladstone Institutes press release

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