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Author Topic: City of Hope - Gene Therapy Update  (Read 2127 times)

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Offline freewillie99

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City of Hope - Gene Therapy Update
« on: January 18, 2009, 12:10:46 PM »
http://www.telegraph.co.uk/scienceandtechnology/science/sciencenews/4276488/Stem-cell-treatment-could-fight-Aids.html

Stem cell treatment could fight Aids

Scientists have claimed a breakthrough in the fight against Aids with a pioneering stem cell treatment that protects the immune system from the virus that causes the disease.
 
By Richard Gray, Science Correspondent
Last Updated: 10:37PM GMT 17 Jan 2009

The ultimate hope is that the pioneering treatment could rid patients of HIV infection entirely Photo: AP
Results of a preliminary trial have raised hopes of a new form of therapy for people suffering from Aids, which occurs in the latter stages of infection with Human Immunodeficiency Virus (HIV). The scientists are planning further research to establish whether the treatment could even rid patients of HIV infection altogether.  The technique involves isolating genes which curb the spread of HIV inside the body, introducing the genes into human stem cells in a laboratory, then transplanting the stem cells into a patient's bone marrow.

In the first human trial, anti-HIV stem cells were transplanted into five Aids patients undergoing bone marrow replacement as part of treatment for a form of cancer known as lymphoma.  Small quantities of the transplanted stem cells were able to grow and produce new white blood cells resistant to HIV, resulting in an improvement in the patients' conditions.  Findings from the trial will be presented this week at the Stem Cell World Congress in Palm Springs, California. It could take up to ten years before an effective clinical treatment could be put into widespread use.

Around 40 million people worldwide are infected with HIV and an estimated three million die each year with the virus. In the UK there are 73,000 people who are living with HIV and in recent years a growing number of heterosexuals have been diagnosed with the infection.  "We are trying to prevent the immunodeficiency that is a result of HIV infection," said Dr David DiGiusto, director of haematopoietic cell therapies at City of Hope Medical Centre in Duarte, California, where the research was carried out.
"It is still an experimental treatment at the moment, but we hope that eventually we will be able to give Aids patients just one transplant and that would then protect them for life.  "We have data to show that the resistant cells are persisting in our lymphoma patients."

HIV, which is a sexually-transmitted infection, attacks white blood cells known as T-lymphocytes, which play a central role in the immune system by fighting other forms of infection.  Over time the number of T-lymphocytes in the body decreases as the virus spreads and the immune system stops working, leading to the condition known as Auto-Immune Deficiency, or Aids, meaning patients are no longer able to fight off infections themselves. Most Aids patients die from pneumonia or cancers such as lymphoma.
Bone marrow contains stem cells that are capable of forming all types of blood cells including the white blood cells that form part of the immune system.

The scientists have found they can import three genes that protect cells against attack from HIV into these blood stem cells in the laboratory.  By giving patients stem cells that carry these anti-HIV genes, the patients' bodies are able to produce new white blood cells that are resistant to attack from HIV and so able to defend the body from other forms of infection.  The trial of the new stem cell therapy was carried out in patients with Aids-related lymphoma as the cancer is commonly treated with a bone-marrow transplant. Powerful drugs are used to strip the patient of their own bone marrow, which is then replaced with cells from a donor.

The doctors behind the research are currently reluctant to expose Aids patients who do not have lymphoma to the risky bone transplant operation, but they are refining the technique in the hope of providing anti-HIV stem cell transplants to all Aids sufferers.  They are due to begin a larger trial where patients will be given greater concentrations of the anti-HIV stem cells in a bid to fight off their condition.
The researchers also hope to develop an intermediate treatment that will allow Aids patients to be given booster injections of HIV resistant white blood cells that would help to improve their ability to fight off infections.

While the ultimate hope is that the pioneering treatment could rid patients of HIV infection entirely, this might not happen if the virus, once it has been prevented from infecting white blood cells, proves able to persist elsewhere in the body.  Dr DiGiusto added: "This is one of the things we are hoping to look at in further work, as well as reducing the toxicity of the conditioning chemotherapy needed to strip the patient of their bone marrow.  "What we are doing is genetically modifying a fraction of the patient's stem cells with genes that target three different aspects of HIV that allow it to get into the immune cells and replicate.  "When those stem cells are transplanted into patients, they create mature immune cells that circulate in the patient and protect against HIV."

The early results have been welcomed by Aids and HIV charities who have described the experimental treatment as "promising".  Annabel Kanabus, director of Aids charity Avert, said: "This is very exciting but clearly it is still in the early stages and has its complications.  "Bone marrow operations are both risky and expensive so for it to be an effective way of treating the millions of people who have Aids, it would need to be something that could be given more like an injection.  "It is possible to make enormous progress in five years and the epidemic is still going to be with us in that timescale."

Dr Marilyn Robertson, network director of the Scottish Stem Cell Network and an Aids expert, said: "This potentially looks very interesting and the combination of multiple genes could tackle the ability for the virus to mutate and get around therapies.  "The research is still in its early stages so clearly there needs to be more work done before it could be used as an effective treatment."

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Offline HALOO

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Re: City of Hope - Gene Therapy Update
« Reply #1 on: January 18, 2009, 12:44:17 PM »
This is the news I am waiting for.I really have big hope in this Gene Therapy and Stem Cell however still long way to go but most promising then anything else.

freewillie99:
                I hope you dont mind, I will add this news into my Gene Therapy and Stem Cell Topic.
               

Offline veritas

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Re: City of Hope - Gene Therapy Update
« Reply #2 on: January 18, 2009, 04:42:40 PM »



 " While the ultimate hope is that the pioneering treatment could rid patients of HIV infection entirely, this might not happen if the virus, once it has been prevented from infecting white blood cells, proves able to persist elsewhere in the body.  Dr DiGiusto added: "This is one of the things we are hoping to look at in further work, as well as reducing the toxicity of the conditioning chemotherapy needed to strip the patient of their bone marrow.  "What we are doing is genetically modifying a fraction of the patient's stem cells with genes that target three different aspects of HIV that allow it to get into the immune cells and replicate.  "When those stem cells are transplanted into patients, they create mature immune cells that circulate in the patient and protect against HIV"

Freewillie99,

This therapy looks promising.  Maybe they could add something to go after that hidden virus. Bavi anyone?

veritas

Offline bimazek

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Re: City of Hope - Gene Therapy Update
« Reply #3 on: January 18, 2009, 06:13:10 PM »

this is really cool, it seems to go along the lines of the german discovery

but in new and more powerful directions

btw

i read somewhere that the reason the hairs turn grey is because the stem cells in the follical that create new baby cells to pigment the hair the stem cells eventually give out and die away

also read about

well stem cells is huge topic

http://en.wikipedia.org/wiki/Stem_cell
http://en.wikipedia.org/wiki/Stem_cell_treatments

Current treatments

For over 30 years, bone marrow, and more recently, umbilical cord blood stem cells have been used to treat cancer patients with conditions such as leukemia and lymphoma. During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents not only kill the leukemia or neoplastic cells, but also the haematopoietic stem cells within the bone marrow. It is this unfortunate side effect of the chemotherapy that the Stem Cell Transplant attempts to reverse; the donor's healthy bone marrow reintroduces functional stem cells to replace those lost in the treatment. In all current Stem Cell treatments obtaining Stem Cells from a matched Donor is preferable to using the patients own. If (always as a last resort and usually because no matched Donor can be found) it is deemed necessary for the patients own stem cells to be used and the patient has not stored their own collection of stem cells (umbilical cord blood), bone marrow samples must therefore be removed before chemotherapy, and are re-injected afterwards


Key research events

1908 - The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874-1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
1968 - Bone marrow transplant between two siblings successfully treats SCID.
1978 - Haematopoietic stem cells are discovered in human cord blood.
1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
1992 - Neural stem cells are cultured in vitro as neurospheres.
1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.[34]
2000s - Several reports of adult stem cell plasticity are published.
2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[35]
2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[36]
2004-2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.
Takahashi K, Yamanaka S (Aug 2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[37][38]
January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[39] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[40]
June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[41] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[42]
October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[43]
November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors",[44] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells":[45] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
January 2008 - Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo[46]
January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[47]
February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS cells seem to be more similar to embryonic stem cells than the previous developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques. [48][49]
March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by Clinicians from Regenerative Sciences[50]
October 2008 - Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation. [51]
30 October 2008 - Embryonic-like stem cells from a single human hair.[52]



Stem Cell Research and Treatment in China
Stem cell research and treatment is actively practiced in China. State funded Chinese Companies based in the Shenzhen Hi-Tech Industrial Zone claim to treat the symptoms of numerous disorders with adult stem cell therapy. Hospitals throughout eastern China provide numerous therapies to patients in coordination with the stem cell providers. These companies' therapies are currently focused on the treatment of neurodegenerative and cardiovascular disorders.
Chinese stem cell research has not been restricted by the ethical dilemmas and legislative gridlock surrounding the procurement and use of human embryonic stem cells in other developed nations such as the US, UK, and Australia. These issues have also hampered the development of adult stem cell research and therapy, as unrelated a cellular origin as they may have. Most stem cell therapies provided in China utilize umbilical cord stem cells (drawn from Wharton's jelly) donated from live births. The stem cells are then expanded in centralized blood banks. Cells are delivered to patients via IV, spinal epidural, subcutaneous injection or transplantation.
While anecdotal evidence of secondary adult stem cell activity has existed for several decades alongside bone marrow transplant therapies, "off-label" uses for stem cells are strictly forbidden in the USA. There, protocols for proposed treatments are described and enforced by the Food and Drug Administration (FDA). In America, the period between laboratory experimentation and clinical treatment can be decades long. Researchers actively treating patients with experimental therapies outside of carefully monitored clinical trials can be subject to harsh disciplinary action by their institutions. The Chinese Ministry of Health has already accepted the use of stem cell therapy for many disorders. After years of practice, stem cell therapy is no longer considered new or dangerous in China and is regularly used by the Chinese in the treatment of the degenerative effects of Multiple sclerosis and Parkinson's disease. International "Medical Tourists" are among the thousands of patients treated in China every year for disorders the patients' home country's medical professionals offer no treatment.


Offline John2038

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Re: City of Hope - Gene Therapy Update
« Reply #4 on: January 19, 2009, 08:45:30 AM »
Interesting key toward a cure.

If we can create a population of white blood cells resistant to HIV (assuming the bone marrow can produce them continuously) then it will become the main white blood cell population. So a step toward a cure.

Just my 2 cents

Offline freewillie99

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Re: City of Hope - Gene Therapy Update
« Reply #5 on: January 28, 2009, 09:52:09 AM »
Further update from City of Hope's presentation last week at the Stem Cell World Congress in Palm Springs.  I've had some correspondence with one of the primary HIV docs there and this sounds quite promising.  Significant progress is being made.

2009-01-26

City of Hope’s stem cell treatment shows promise against AIDS

DUARTE, Calif. —Working with four lymphoma patients whose bone marrow had been killed via chemotherapy, a team led by Dr. David DiGuisto, director of haematopoietic cell therapies at City of Hope Medical Center in Duarte, Calif., has demonstrated promising results from subsequent treatment with genetically altered stem cells. The scientists are planning further research to establish whether the treatment might rid patients of HIV infection altogether.

The technique involves introducing genes that curb the spread of HIV inside the body into human stem cells, then transplanting the stem cells into a patient’s bone marrow. In the first human trial, anti-HIV stem cells were transplanted into the four AIDS patients undergoing bone marrow replacement as part of treatment for lymphoma. The stem cells, DiGuisto says, are a mixture of genetically altered cells and “a sufficient dose of unmanipulated stem cells.” The protocol calls for no less than 2 million cells per kilogram of body weight. “Our best estimate,” DiGuisto adds, “is that about one percent of the cells are of the genetically altered type.” All four infused patients are in remission for lymphoma with no recurrence of HIV.

Presenting his finds from the trial at the Stem Cell World Congress in Palm Springs, Calif., DiGuisto described his work as “A first-in-humans study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentiviral vector encoding multiple anti-HIV RNAs.” Unanswered at this time is the fate of the 99 percent of the stem cells that were infused without the protecting treatment. The hope is that, in a sort of “survival of the fittest” at the cellular level, the treated stem cells will proliferate and take over.

“We are currently doing two things to improve the process,” DiGuisto says. “First, we are seeking approval of a protocol to introduce 100 percent of the modified stem cells. A second approach would be to introduce the same modified genes into T-lymphocytes of HIV patients. We have data to show that the resistant cells are persisting in our lymphoma patients. It is still an experimental treatment, but we hope that eventually we will be able to give AIDS patients just one transplant that would protect them for life.”

The next step is to repeat the first-in-human trial in five to 10 patients, DiGuisto adds, and then to increase the cohort to between 30 and 50 individuals.

Around 40 million people worldwide are infected with HIV and an estimated three million die each year with the virus. HIV attacks white blood cells known as T-lymphocytes, which play a central role in the immune system by fighting infection.

City of Hope is one of 40 National Cancer Institute-designated Comprehensive Cancer Centers nationwide and a founding member of the National Comprehensive Cancer Network. An independent biomedical research, treatment and education institution, it is dedicated to the mission of conquering cancer, diabetes, HIV/AIDS and other life-threatening diseases.

http://www.drugdiscoverynews.com/index.php?newsarticle=2720
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