November 24, 2005
Another Gene Therapy Treatment For HD
Neurologix, another struggling biotech company, has a promising gene therapy treatment for Huntington's Disease that has done well in pre-clinical testing. From their press release:
Neurologix, Inc. today announced findings from preclinical studies, which showed that the gene XIAP (X-linked inhibitor of apoptosis) may prevent the progression of Huntington's disease. Neurologix scientists demonstrated that a mutated form of the gene delivered by an adeno-associated virus (AAV) vector, introduced using standard neurosurgical techniques can improve motor deficits associated with the disease. ...Using cell culture models of the disease, the researchers showed that a truncated form of XIAP lacking the RING domain (RING) may significantly reduce cell death caused by a mutated form of human huntingtin gene.
The researchers further investigated the neuroprotective effects of dXIAP in a transgenic animal model by injecting presymptomatic mice with AAV vectors encoding dXIAP into the striatum, an area of the brain largely affected in Huntington's patients. In the study, mice injected with this vector experienced significant protection from motor dysfunction when compared to mice treated with a control vector. dXIAP also appeared to prolong the life-span of the mice by 16%. Furthermore, no adverse effects due to dXIAP over-production were observed.
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July 09, 2005
Amish Involved In Genetic Research
The Toronto Globe and Mail has a fascinating article on the Amish and their involvement with genetic research.
"It's weird and it's wonderful," said Terry Sharrer, medical curator of the Smithsonian Institution in Washington D.C. "I have never seen anything like this."The children's clinic is the creation and life's work of Dr. Holmes Morton and his wife Caroline. The Harvard-educated couple surprised colleagues and friends in 1987 when they announced they were giving up prestigious urban posts in Philadelphia, packing up the family and starting a new life among the Amish and Mennonite religious sects.
It's a place where the laundry of plain clothes flaps in the breeze and barefoot children in smocks and straw hats run around homes shared and passed down by multiple generations. Road signs warn drivers to share the road with the horses and buggies.
Morton hasn't regretted the move.
"We discover a new gene almost weekly," he said.
Isolated populations with homogenous genes such as the Amish in central Pennsylvania, the Ashkenazi Jews and Indian tribes offer genetic researchers unparalleled insight into disease and genetics.
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July 07, 2005
Molecular Trigger For Huntington's Disease Found
That's the headline of a press release for a study published in the journal "Neuron".
Every day researchers understand Huntington's Disease better and better. And, once again, the research shows potential to help in the treatment of other diseases.
Here's the press release:
Molecular trigger for Huntington's disease found
Researchers have discovered a key regulatory molecule whose overactivation by the abnormal protein produced in Huntington's disease (HD) causes the central pathologies of the disease. The abnormal HD protein activates the regulatory protein called p53, which in turn switches on a host of other genes. This abnormal gene activation damages the cells' power plants, called the mitochondria, and kills brain cells.
The researchers also speculated that disturbances in p53 may also play a role in some forms of Parkinson's disease and amyotrophic lateral sclerosis, or Lou Gehrig's disease.
Ironically, p53 is the same regulatory protein that is inactivated in a large fraction of cancers. This inactivation allows abnormal cancer cells to escape the cell's protective "suicide program" that would normally kill them. The researchers theorize that the lower incidence of cancer in HD patients could be caused by the protective effect of overactive p53.
In the July 7, 2005, issue of Neuron, Akira Sawa and colleagues at Johns Hopkins University School of Medicine reported experiments ranging from molecular studies in cultured brain cells to analysis of the brains of human HD patients that demonstrated the central role of p53 in the pathologies of HD.
Their studies with cell cultures showed that the abnormal HD protein selectively binds to p53 and increases its level in cells. They noted that the brains of patients with HD also show substantial increases in the p53 protein, with the highest levels in cases with the most extensive pathology.
The researchers' experiments also revealed that this p53 increase causes an overactivation in the genes regulated by p53, which is called a "nuclear transcription factor" because it regulates the transcription of its target genes in cell nuclei.
In studies of cell cultures and of mice engineered to have HD, the researchers found that the p53 increase causes malfunctions in mitochondria. What's more, they found that this p53 increase induced by the abnormal HD protein greatly increases cell death.
The researchers also found effects of the abnormality in p53 in whole animals. They found that deleting p53 suppresses damage to neurons in the eye of fruit flies engineered to have the abnormal HD protein. And in mice with the abnormal protein, knocking out p53 corrects behavioral abnormalities that the mice otherwise display. These behaviors include abnormal reflexes such as an inhibited startle response to loud noise, which is also present in human HD patients.
"In summary, our study establishes a specific role for p53 in HD," concluded Sawa and colleagues. "As p53 is a nuclear transcription factor that regulates various mitochondrial genes and insofar as mitochondrial dysfunction appears important in HD, our findings provide a molecular mechanism linking disturbances of nuclei and mitochondria in HD." Download PDF
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The researchers include Byoung-Il Bae, Hong Xu, Shuichi Igarashi, Masahiro Fujimuro, Nishant Agrawal, Yoichi Taya, S. Diane Hayward, Timothy H. Moran, Craig Montell, Christopher A. Ross, Solomon H. Snyder, and Akira Sawa of Johns Hopkins University School of Medicine. This study was supported by USPHS grants; foundation grants; Huntington's Disease Society for America grant, Hereditary Disease Foundation grant, Stanley, NARSAD award, S-R; Korea Foundation for Advanced Studies Predoctoral Fellowship.
Byoung-Il Bae, Shuichi Igarashi, Masahiro Fujimuro, Nishant Agrawal, Yoichi Taya, S. Diane Hayward, Timothy H Moran, Christopher A Ross, Solomon H Snyder, Akira Sawa: "p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington's Disease" DOI 10.1016/j.neuron.2005.06.005 Publishing in Neuron, Volume 47, July 7, 2005, pages 29-41. http://www.neuron.org/
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April 08, 2005
Another Great Advance In Research
The rapid advance of science amazes me. The implications of this amazing bit of research for curing Huntington's Disease are obvious...
A team led by scientists at Sangamo Biosciences in Richmond, California, US, say they have corrected the single gene mutation that causes the fatal X-chromosome-linked severe combined immune deficiency (X-SCID) - or “bubble boy” disease - in human T-cells. They treated the cells in test tubes with the company’s proprietary type of “zinc finger nucleases” (ZFNs) and have published their results in Nature.ZFNs are proteins made up of “fingers” of around 30 amino acids and stabilised by a zinc atom. Each finger binds to a specific combination of DNA bases and is attached to a DNA-cutting enzyme called a nuclease.
By using different combinations of amino acids, they can be designed to latch on to DNA at exactly the place where the mutated gene lies and cut it. This triggers the body’s natural repair process, called homologous recombination, which corrects the gene where the DNA was cut, The researchers provided the cells with a copy of the correct gene as a template.
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April 05, 2005
Another Success for RNAi
The University Of Iowa is leading the world again in the race to treat Huntington's Disease. They just did a mouse model test using RNAi to target the huntingtin gene. Here's the money quote from their press release:
Detailed examination of the protein levels in the treated mice showed that levels of the toxic HD protein were reduced to about 40 percent of the level seen in untreated mice.
They have more animal testing to do before it goes to human tests but this is very good news! Here's the full press release:
U. Iowa researchers improve Huntington's disease symptoms in mice
Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine have taken another step toward a potential treatment for Huntington's disease (HD). Using an approach called RNA interference (RNAi), the scientists reduced levels of the disease-causing HD protein in mice and significantly improved the movement and neurological abnormalities normally associated with the disease.
HD is a devastating, inherited, neurodegenerative disease that is progressive and always fatal. The disease-causing gene produces a protein that is toxic to certain brain cells, and the subsequent neuronal damage leads to the movement disorders, psychiatric disturbances and cognitive decline that characterize this disease.
"Many of the current approaches aimed at treating HD are indirect and target the symptoms of the disease. RNA interference gives us the first opportunity to attack the fundamental problem and reduce protein expression from the disease gene," said Beverly L. Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "Our study is the first demonstration that a therapy designed to inhibit protein production has a beneficial effect."
The study will appear this week in the Online Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org). Davidson is the senior author and Scott Harper, Ph.D., a postdoctoral researcher in Davidson's lab, is lead author.
Harper, Davidson and their colleagues used RNAi to treat a mouse model of HD. Viral vectors (stripped-down viruses) carrying the genetic instructions to make a RNA interference molecule were injected into the brains of genetically engineered mice before the disease symptoms appeared. The treated mice showed nearly normal movement, and the characteristic neurological damage also was significantly improved in comparison to untreated mice.
Detailed examination of the protein levels in the treated mice showed that levels of the toxic HD protein were reduced to about 40 percent of the level seen in untreated mice.
"It is very exciting that a partial reduction is sufficient to produce a very beneficial effect in the animal. It means that we don't have to turn the gene off completely," Davidson said. "For a disease that takes decades to develop, a partial reduction may slow down the disease-causing copy of the gene to such an extent that either disease progression is delayed or possibly even disease onset is prevented."
It may even be the case that a partial reduction of toxic protein levels allows the brain cells' machinery to "catch up" with the disease-causing protein and clear out the damage caused by the mutant protein.
The genetically engineered or transgenic mouse model used by the UI team carries a section of the human HD gene. These mice quickly develop movement and coordination abnormalities and they die young. Aggregates, or clumps of protein, also develop in certain brain cells.
Davidson explained that this mouse is very good for proof-of-principle experiments, allowing the researchers to ask a very pointed question – can RNAi improve HD-like symptoms in a mouse model in short order?
"Since our results are positive, we can now repeat the experiment in mouse models that develop disease more slowly and more closely resemble HD in humans," Davidson said.
Most genes are inherited as a pair, one from either parent. In HD, one mutated copy of the gene is sufficient to cause the disease. However, the normal Huntington gene produces a protein that is known to be critical in embryonic development. It is not known if the protein is critical in adult brain cells.
The RNAi molecule used in Davidson's current study would silence both the mutant and the normal gene. So, an important question that still needs to be addressed is whether adult neurons can tolerate and benefit from a partial reduction of both the toxic and the normal protein. If the normal protein is critical, then RNAi will need to be specifically targeted against the disease-causing gene.
Fortunately, RNAi is exactly the right tool to provide an answer regarding whether the normal gene is critical by silencing the normal gene in adult brain cells of HD models.
Despite the remaining hurdles, Davidson is optimistic about the potential of RNAi to treat HD and similar neurodegenerative diseases.
"If the benefit is confirmed in other mouse models of Huntington's disease, and it appears that we don't need to target the RNAi specifically to the disease-causing mutant gene, then I would think it might move to human testing within several years," she said.
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The study was funded by the NIH, the Cure HD Initiative and the Hereditary Disease Foundation.
In addition to Davidson and Harper, the UI team included Patrick Staber, Xiaohua He, Steven Eliason, Ines Martins, Qinwen Mao, Ph.D., and Henry Paulson, M.D., Ph.D., associate professor of neurology. Robert Kotin, Ph.D., and Linda Yang at the National Heart, Lung and Blood Institute, also were part of the research group.
University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.
STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178
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January 25, 2005
RNAi Trials May Start Next Year
Sirna Therapeutics has provided more news on their promising RNAi treatment for Huntington's Disease.
It looks like Phase 1 human trials may start next year! For those of you who have been following this blog...I believe this treatment has an excellent chance of being the effective/treatment for HD that we've been waiting for.
Here's the key quote from the press release:
Sirna's second program in local delivery is focused on Huntington's Disease, a life-threatening brain disorder accounting for more than $2 billion in patient costs annually in the U.S. Sirna recently entered into a collaboration with Targeted Genetics for the development of adeno-associated viral (AAV) vector delivery of siRNAs that target the expression of Huntington's protein, which in its mutant form causes the disease. Sirna is also collaborating with the Huntington's Disease Society of America and with Dr. Beverly Davidson at the University of Iowa, who has published promising data in this area. Sirna expects to file its Investigational New Drug (IND) application with the FDA in 2006 and to begin the first trial in HD using siRNAs shortly thereafter.And here's the full press release:
Sirna Therapeutics Establishes Broad Product Pipeline in RNAi for Systemic, Local and Topical Therapies
Company Expects One Phase 2 Program, Three Phase 1 Programs in 2006
Tuesday - January 25, 2005
BOULDER, Colo., Jan. 25 /PRNewswire-FirstCall/ -- Sirna Therapeutics, Inc. announced that the Company is advancing six major programs in its broadly diversified, clinical-stage product pipeline. Sirna's pipeline demonstrates the vast opportunity of short interfering RNAs (siRNAs) in systemic, local and topical delivery, enabling the Company to address serious unmet medical needs (Huntington's Disease), major disease markets (asthma and diabetes) and novel commercial programs (hair removal). Key programs are also focused on age-related macular degeneration (AMD), Sirna's first program to enter Phase I clinical testing, and oncology, through a collaboration with Eli Lilly.
Howard Robin, Sirna's President and Chief Executive Officer, stated, "The Sirna product pipeline addresses multi-billion dollar global markets across diverse disease targets, allowing us to reduce risk while at the same time attract multiple partners. Notably, we have entered into collaborations with Eli Lilly in oncology and Targeted Genetics in Huntington's Disease, and acquired Skinetics Biosciences to form our dermatology division. Each relationship has contributed to our development of what we believe is the most advanced and comprehensive pipeline in RNAi."
Mr. Robin continued, "Sirna is at a unique and pivotal point in its history. Having initiated our first clinical trial in AMD in November of 2004, we now have many near-term opportunities for positive news flow and value creation. In 2006, we expect to be advancing our lead AMD program into Phase 2 clinical testing and to have progressed three additional programs into Phase 1 clinical trials. Coupled with additional corporate partnerships that we expect to announce in 2005, we are in a great position to continue to communicate our value to the investor community and other key audiences."
Sirna's proprietary pipeline is rapidly advancing products for local, systemic and topical delivery:
Local Delivery (Age-Related Macular Degeneration, Huntington's Disease, Asthma)
Sirna's first program to advance into the clinic targets age-related macular degeneration, a degenerative eye disease that is the leading cause of blindness in the elderly in the United States. By 2010, over $1.5 billion is expected to be spent annually in the U.S. alone for therapies that treat AMD. In November 2004, Sirna initiated Phase 1 testing of Sirna-027, an siRNA targeting Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1), which is a key component of the clinically validated vascular endothelial growth factor (VEGF) pathway. Sirna expects to announce results of the Phase 1 study by the end of 2005 and to initiate a Phase 2 clinical trial in 2006.
Sirna's second program in local delivery is focused on Huntington's Disease, a life-threatening brain disorder accounting for more than $2 billion in patient costs annually in the U.S. Sirna recently entered into a collaboration with Targeted Genetics for the development of adeno-associated viral (AAV) vector delivery of siRNAs that target the expression of Huntington's protein, which in its mutant form causes the disease. Sirna is also collaborating with the Huntington's Disease Society of America and with Dr. Beverly Davidson at the University of Iowa, who has published promising data in this area. Sirna expects to file its Investigational New Drug (IND) application with the FDA in 2006 and to begin the first trial in HD using siRNAs shortly thereafter.
Sirna is also developing a drug candidate for local delivery to treat asthma, representing a $13.3 billion market opportunity in the U.S. Sirna is working with Dr. Erwin Gelfand of the National Jewish Medical & Research Center to test an siRNA that targets Th2 cytokines, which play a critical role in inflammation and bronchconstriction in the airways. Early preclinical findings have shown a statistically significant reduction of airway hyperresponsiveness (66%) in an RNAi treatment group. An IND filing for this product is anticipated in 2006.
Systemic Delivery (Diabetes, Oncology)
Type II diabetes is a $6.3 billion market in the United States, and the market is growing. Sirna researchers have shown that administration of a systemically delivered siRNA resulted in a 72% reduction of PTP-1B (phosphatase 1B), a validated target in diabetes that is associated with insulin resistance. Other pioneering work at Sirna has demonstrated that up to 30% of administered siRNAs get into hepatocytes, liver cells that are the main target in treating diabetes. The Company plans to file its IND in diabetes in 2007.
In January 2004, Sirna initiated a collaboration with Eli Lilly and Company to apply Sirna's RNAi technology against Lilly's proprietary models in oncology. To date, the collaboration has demonstrated target mRNA and protein knockout in three tumor cell lines and an effect of siRNAs at the molecular level. Demonstration of in vivo target knockdown is currently in progress.
Topical Delivery (Dermatology)
In December 2004, Sirna launched its dermatology division following the acquisition of Skinetics Biosciences. Skinetics founder, Dr. Angela Christiano of Columbia University, is now an exclusive consultant to the Company. Sirna's first dermatology program is focused on the removal of unwanted hair, accounting for an estimated $4 billion dollar market in the U.S. (excluding shaving). The Company is in the preclinical stages of developing an siRNA targeting the "hairless" protein, so-called because people who have a nonfunctional version of this protein do not grow any hair. Sirna believes that infrequent treatments with an siRNA targeting the "hairless" protein could achieve results comparable to those seen in laser hair removal with less inconvenience and discomfort to the patient. An IND filing for the hair removal product is expected in 2006.
About Sirna Therapeutics
Sirna Therapeutics is a clinical-stage biotechnology company developing RNAi-based therapies for serious diseases and conditions, including age-related macular degeneration (AMD), Huntington's Disease, diabetes, asthma, oncology, and hair removal. Sirna has initiated a Phase 1 clinical trial for its most advanced compound, Sirna-027, a chemically modified siRNA targeting the clinically validated vascular endothelial growth factor pathway to treat AMD. The Company has strategic partnerships with Eli Lilly, Targeted Genetics and Archemix and a leading intellectual property portfolio in RNAi. More information on Sirna Therapeutics is available on the Company's web site at http://www.sirna.com/.
Statements in this press release which are not strictly historical are "forward-looking" statements which should be considered as subject to many risks and uncertainties. For example, there is a very significant risk that promising pre-clinical results cannot be reproduced in the clinic. Furthermore, Sirna's ability to develop products and to operate as a going concern are contingent upon having readily available cash to fund its operating programs and are subject to the escalating expenses and risks associated with the initiation of clinical trials and their potential outcomes. Other risks and uncertainties include Sirna's early stage of development and short operating history, whether Sirna can achieve and maintain profitability, whether Sirna can obtain and protect patents, the risk of third-party patent infringement claims, whether Sirna can engage collaborators and obtain regulatory approval for products, Sirna's concentration of stock ownership, and availability of materials for product manufacturing. These and additional risk factors are identified in Sirna's Securities and Exchange Commission filings, including the Forms 10-K and 10-Q and in other SEC filings. Sirna undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.
CONTACT:
Martin E. Schmieg, Sr. Vice President & CFO of Sirna Therapeutics, Inc., +1.303.449.6500Web site:
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January 02, 2005
Gene Article
As I read this excellent article on gene testing one thought came to mind...
"What about genetic discrimination?"
We need a white knight in congress who will push for a genetic anti-discrimination bill. Doing it sooner, rather than later, will save lives.
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October 06, 2004
DNA & 'Cures"
Remember the discussions after the HD gene was found in 1993? There was a lot of enthusiasm and many believed "that a cure is right around the corner."
That was 11 years ago. What researchers have since found was...how much they didn't know. I'm amazed at just how much has been learned in just the last three years alone. Each discovery is quickly building on each other.
Derek Lowe has another excellent article on his blog called "DNA to Drug?" which gives an insiders view to the difficulties researchers are facing.
His article reflects the frustion that the pharmaceutical industry has faced in turning DNA knowledge into treatments. In a nutshell - it ain't easy folks.
We're fortunate in that Huntington's Disease is single-gene disease & that we've had a few researchers, such as Dr. Nancy Wexler, who've done unbelievable work.
In our corner of the DNA/drug world, I've very excited and I believe the RNAi research coming out of the University of Iowa will ultimately lead to a very effective treatment for Huntington's Disease. But that is still 6-9 years away from reality (i.e. FDA approval) and, should it happen, HD would be one of the earliest diseases 'cured' in such a manner. That's 20 years after the discovery of the gene.
Derek's right, converting DNA knowledge into drugs is tough work. But the effort will be worth it. Twenty, thirty, fifty years from now historians will look back with amazement at the technologies that were developed and the diseases that were 'cured'. And that will be because of the hard work done by Derek and thousands of other researchers.
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September 15, 2004
First Human Testing For RNAi
Not for Huntington's Disease, but for Macular Degeneration. To me it is amazing how fast research is moving on using RNAi as a therapeutic tool.
I've said it before and I'll say it again...RNAi will probably become one of the biggest medical stories of the last several decades. It offers the biggest hope for to be a truly effective Huntington's Disease effective treatment/'cure' in the near future. Just one of many diseases that may end up being treated with this method.
Oh...Sirna Therapeutics, which is working with the University of Iowa on a treatment for Huntington's Disease, is also applying to the FDA for approval to use RNAi in the treatment of Macular Degeneration. An excerpt from this very interesting article:
Backers, though, say that RNAi appears to be more potent than the earlier techniques because it makes use of the cell's natural mechanism.
"There's no doubt in my mind that this is the clear winner," said Mark A. Kay, a Stanford professor. He hopes to test an RNAi treatment for hepatitis C in cooperation with Benitec, an Australian company that now owns a company he founded.
Some animal tests have demonstrated the technique's potential. According to a paper published in June, scientists at the F.D.A. led by Suzanne L. Epstein used RNAi to partly protect mice from lethal flu viruses, including two strains of avian flu that experts worry could become the basis for a new pandemic.
Beverly L. Davidson and colleagues at the University of Iowa reduced the severity in mice of one type of ataxia, a hereditary brain disease somewhat similar to Huntington's. "It's very exciting,'' she said, "because we finally have a tool to approach therapies" for diseases like Huntington's and ataxia.
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August 12, 2004
Starfish Gene
Check out this article from the New Zealand Herald. Scientists are using a gene from the starfish in an attempt to regenerate cells.
The lead of the story points to the goal of regenerating limbs, but look at this little piece at the end of the article:
Auckland University Professor Garth Cooper said New Zealand researchers hoped to use similar techniques to regenerate brain cells in patients with degenerative conditions such as Huntington's disease.
It never ceases to amaze the growth in medical research.
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August 01, 2004
Another Article On The Breakthrough
One of the best article,s yet, this one from The Independent, on the genetic therapy success out of the University of Iowa. Here's the highlights from the article:
In a groundbreaking study, scientists have shown for the first time that it is possible to stop a progressive brain disease in mice with a genetic technique known as RNA interference (RNAi).
Dr Davidson said that the findings, published in this month's Nature Medicine, were among the most important results of her career because they demonstrated the possibility of directly attacking the faulty gene responsible for Huntington's disease. "I'm extremely excited about the potential of RNAi and cautiously optimistic about its possible use in human medicine," Dr Davidson said.
"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies," Dr Davidson said. "We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier," she said.
Nancy Wexler of Columbia University in New York, a world authority on Huntington's disease, said RNAi offers the most promising potential treatment for the disease she has seen. "When I first heard of this work, it just took my breath away. Its everything you ever wanted to hear and more," said Professor Wexler, president of the Hereditary Disease Foundation in New York and a member of the team that originally discovered the Huntington's gene.
Phillip Sharp, a Nobel laureate from the Massachusetts Institute of Technology in Boston, said Dr Davidson's findings were "striking" because they demonstrated that RNAi may work for human patients suffering from a range of debilitating brain diseases. "It shows that, in the context of the biology, it's possible to do. This is a significant step, there's no doubt about it," Professor Sharp said.
The big question was whether this ability to silence genes could be "delivered" to all the cells of the body that needed it. Beverly Davidson's work shows that in a mammal the delivery of RNAi can work, even across the notoriously difficult biological barrier that protects the brain. She used a harmless carrier vehicle called adeno-associated virus to take the RNAi molecule into the diseased cells of the brain where the defective Huntington gene needed to be silenced. It worked.
"The broader science of RNAi is spectacular. Its just absolutely spectacular," Professor Sharp said.
"This is not hype. The biggest science prizes in the world will fall to RNAi."
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July 07, 2004
More On RNAi Breakthrough
There has been many articles written about the RNAi treatment that cured a disease similar to Huntington's (in mice). However, this article from Drug Researcher sheds some additional information that is written in a more understandable format. The highlights:
"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies,"
"We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier."
An additional finding by the researchers was that RNA interference in and of itself does not appear to be toxic to normal brain cells. The study demonstrated that neither animal behaviour nor brain structures were affected by RNA interference gene therapy.
Davidson said: As yet, we have noted no unwanted side effects. RNAi in normal mice was not detrimental, it did not induce behavioural or morphological problems using the assays described in the paper.
The study additionally revealed the specific vectors used to target those cells that are most involved in causing the disease symptoms. The vector used in this study, specifically targeted Purkinje cells, essential for movement and coordination.
Davidson explained: "Choosing the right vector for the right cells could help us limit gene expression to those cells where altering expression will have a beneficial effect.
Davidson told DrugResearcher.com that currently there was no date set for human trials as the research was only at a basic research stage. However they were looking toward initiating studies in larger mammals.
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July 05, 2004
More On The SCA1 Success
As was reported here earlier, the University of Iowa had success curing SCA1 in mice. This is important news as SCA1, like Huntington's Disease, is a polyglutamine disease. It's too-long string of CAG repeats is just in a different location. Yesterday, the journal Nature Medicine, published the study online in advance of it's printed release.
Sirna Therapeutics is working with one of the study's authors on developing this therapy for Huntington's Disease. They do have to redesign the treatment in order for it to work on HD but, in my amateur opinion, I believe they will be successful.
Here is the University of Iowa's press release:
Combination of gene therapy and gene silencing prevents neurodegenerative disease
University of Iowa researchers have shown for the first time that gene therapy delivered to the brains of living mice can prevent the physical symptoms and neurological damage caused by an inherited neurodegenerative disease that is similar to Huntington's disease (HD).
If the therapeutic approach can be extended to humans, it may provide a treatment for a group of incurable, progressive neurological diseases called polyglutamine-repeat diseases, which include HD and several spinocerebellar ataxias. The study, conducted by scientists at the UI Roy J. and Lucille A. Carver College of Medicine and colleagues at the University of Minnesota and the National Institutes of Health (NIH), appears in the August issue of Nature Medicine and in the journal's advanced online publication July 4.
"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies," said senior study author Beverly Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier."
Davidson and her colleagues used a viral vector (a stripped-down virus) to deliver small fragments of genetic material (RNA) to critical brain cells of mice with a disorder that mimics the human neurodegenerative disease spinocerebellar ataxia 1 (SCA1). The genetic material suppresses the disease-causing SCA1 gene in a process known as RNA interference.
Mice with the SCA1 gene that were treated with the gene therapy had normal movement and coordination. The gene therapy also protected brain cells from the destruction normally caused by the disease and prevented the build-up of protein clumps within the cells. In contrast, mice with the SCA1 disease gene that were not treated developed movement problems and lost brain cells in a manner similar to humans with this condition.
Both SCA1 and Huntington's disease are members of a group of neurodegenerative disorders caused by a particular type of genetic flaw. In these dominantly inherited diseases, a single mutated gene inherited from either parent produces a protein that is toxic to cells. Thus, a successful therapy must remove or suppress the disease-gene rather than simply add a corrected version.
"Although we know how to put genes into cells, the difficulty we face in treating dominant diseases is how to remove or silence genes," Davidson explained. "With our approach we can marry our gene therapy research using viral vectors with RNA interference."
Silencing the SCA1 gene with RNA interference inhibited the production of a neurotoxic protein, suggesting that this technology may also be helpful against other degenerative neurological diseases caused by neurotoxic proteins, such as Alzheimer's disease.
In addition to the finding that RNA interference inhibited gene expression to such an extent that it protected the animals against the disease, another important finding was that RNA interference in and of itself does not appear to be toxic to normal brain cells. In the UI study, neither animal behavior nor brain structures were adversely affected by RNA interference gene therapy.
Furthermore, the study revealed that specific properties of different gene therapy vectors can be used to target those cells that are most involved in causing the disease symptoms. In this case, the UI team proved that their gene therapy vector, adeno-associated virus 1, specifically targeted Purkinje cells, which are very important for gait and coordination.
"Choosing the right vector for the right cells could help us limit gene expression to those cells where altering expression will have a beneficial effect," Davidson explained.
Davidson is optimistic about the potential for using RNA interference gene therapy to treat neurological diseases like HD and spinocerebellar ataxias in humans.
"This is among the most important work I have done and I am excited about the prospect of helping to move this approach into clinical trials," she added.
In addition to Davidson, the team included UI researchers: Haibin Xia, Ph.D., and Qinwen Mao, Ph.D., who were co-lead authors of the study; Henry Paulson, M.D., Ph.D.; Steven Eliason; Scott Harper, Ph.D.; and Ins Martins. Harry Orr, Ph.D., at the University of Minnesota, and Linda Yang and Robert Kotin, Ph.D., at the NIH also were part of the team.
Davidson first presented these findings at the American Society of Gene Therapy meeting in May, where it was nominated the top abstract.
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The study was funded in part by the NIH, the Hereditary Disease Foundation and the Roy J. Carver Charitable Trust.University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.
STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178
CONTACT(S): Jennifer Brown, (319) 335-9917, jennifer-l-brown (at) uiowa (dot) edu
PHOTOS/GRAPHICS: Photos for this story are available for downloading at http://www.medicine.uiowa.edu/Davidsonlab/bio.htm
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July 02, 2004
RNAi As A Huntington's Treatment
I've got wonderful readers on this website! Thanks to the reader who kindly posted the link to the article mentioned yesterday on RNAi.
In a nutshell, this article talks about research using RNAi as the way to 'cure' Huntington's Disease. This lab is in the early stages of Huntington's/RNAi research. They are working on proving the concept that their RNAi method will work on the huntingtin protein. Then they will start testing various methods of delivering their treatment - one of which includes surgery.
They figure they've got at least three years of animal testing so this particular lab is still many years away from providing a cure. This is all very exciting stuff!
These disorders, of which Huntingtons disease is one, are caused by the expansion of triplet repeat DNA sequences, Tiscornia said. Specifically, Huntingtons disease is caused by the expansion of a CAG repeat in exon 1 of the gene huntingtin.
The traditional approach in gene therapy is to find a disease caused by a protein being mutated, and then providing that protein through a lentiviral vector finding something that is not there and then giving it back, Tiscornia explained. In these diseases, the problem is the opposite so RNAi was, on paper, perfectly suited for this.
Tiscornias project, the first of its kind in the Verma lab, is looking to establish a proof of concept that siRNAs targeting huntingtin and delivered using lentiviral vectors can slow or halt the progression of Huntingtons disease in a transgenic mouse model of the disease.
...
Were testing the limits of the technology, he added. Once we know what those limits are, then we can think about what to do later.
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RNAI Website
A reader points out a website I wasn't familiar with: www.rnainews.com.
They have an article titled "Salk Researcher Joins the Ranks of Those Looking at RNAi as a Huntingtons Treatment".There isn't access to the article at the moment, but this looks to be a website worth watching. In my opinion, RNAi offers the best & quickest route to a 'cure' for Huntington's Disease and many researchers are trying to do just that.
Posted by Dave at 07:08 AM | Comments (1) | TrackBack
June 10, 2004
More On The Gene Therapy News
The journal Nature has the best writeup yet that I've seen on the University of Iowa's breakthrough. The title of the article is Cure Hoped For Huntington's Sufferers.
Here are excerpts from the article:
"Most gene therapy involves replacing a missing gene sequence. But in dominant disorders it is the mutant sequence itself that causes the problem, so any therapy needs to actively block a sequence rather than just replacing one.
To do this in the mice, Davidsons team used a technique called RNA interference. The researchers isolated pieces of genetic material that bind to and block the mutant gene. They packaged these into stripped-down virus particles and injected them into the mice. The virus used was an adeno-associated virus that does not cause disease in mice or people.
After the injections, the proteins created by the mutant gene disappeared and the mice seemed to improve, the researchers told the annual meeting of the American Society of Gene Therapy in Minneapolis, Minnesota last week.
....
Davidson says she hopes that her technique will move quickly into clinical trials. The data are very promising; we hope we will be able to use RNA interference as a therapy for dominant neurodegenerative diseases.Posted by Dave at 04:26 PM | Comments (0) | TrackBack
June 08, 2004
More Good News
Just a few days ago I posted the 'Success' article on the University of Iowa's success with using RNAi to successfully treat a disease very similar to Huntington's disease.
Today Sirna Therapeutics has announced that they are collaborating with the University of Iowa on pursuing this RNAi treatment on Huntington's Disease. They have already successfully tested this in the petri dish and are currently in the process of testing 'in-vivo' (most likely HD mice).
All signs point to Sirna making this a development priority and they also appear to be financially capable to bring this therapy to market. Assuming successful in-vivo testing (very likely), we could see Phase I human tests with 18-24 months. This treatment would qualify for FDA 'fast track' testing.
We are getting closer!
Tuesday June 8, 8:55 am ET
Sirna Licenses Fundamental Intellectual Property on CNS Targets for RNAi TherapeuticsBOULDER, Colo., June 8 -- Sirna Therapeutics, Inc. (Nasdaq: RNAI - News) today will announce in a corporate presentation at the BIO 2004 Annual International Convention that the Company is evaluating the potential application of RNA interference-based therapies in diseases of the central nervous system (CNS), specifically, Huntington's Disease. Sirna has initiated a research collaboration with Dr. Beverly Davidson, Roy J. Carver Professor in Internal Medicine at the University of Iowa. Sirna has already demonstrated siRNA-mediated knockdown of Huntington's Disease gene expression in cell culture in collaboration with Dr. Davidson and efficacy studies in validated in vivo models are currently in progress. In addition, Sirna has in-licensed key patents from the University of Iowa Research Foundation covering neurological disease targets using RNAi technology, including those relating to Huntington's Disease. This license combined with Sirna's broad intellectual property on RNAi technology and Huntington's Disease provides Sirna a strong patent position in this important therapeutic area.
Howard Robin, Sirna's President and Chief Executive Officer, commented, "We believe that localized delivery of siRNAs may be an effective means of addressing devastating diseases of the CNS. In the case of Huntington's Disease, there is a clearly validated target to attack with siRNAs -- the polymorphisms in the Huntington's Disease gene. This builds on our strategy of applying our expertise in RNA chemistry, biology and pharmacology to validated therapeutic targets in areas of significant unmet medical need. Dr. Davidson is one of the leading scientists in the field of Huntington's Disease research, and we are very excited to be collaborating with her in this program."
About Sirna Therapeutics
Sirna Therapeutics is using its proprietary technology and expertise in nucleic acids to develop a new class of nucleic acid-based therapeutics involving RNA interference. RNAi is a mechanism used by cells to regulate the expression of genes and replication of viruses. The RNA interference mechanism uses short interfering RNA (siRNA) to induce the destruction of target RNA using naturally occurring cellular protein machinery. Harnessing the natural phenomenon of RNAi holds potential for the development of a new class of drugs with specificity towards a wide range of diseases that result from undesirable protein production or viral replication. More information on Sirna Therapeutics is available on the company's web site at www.sirna.com.
Statements in this press release which are not strictly historical are "forward-looking" statements which should be considered as subject to many risks and uncertainties, including early stage of development and short operating history, ability to achieve and maintain profitability, ability to obtain and protect patents, risk of third-party patent infringement claims, ability to engage collaborators, ability to obtain regulatory approval for products, concentration of stock ownership, and availability of materials for product manufacturing. These and additional risk factors are identified in the Company's Securities and Exchange Commission filings, including the Forms 10-K and 10-Q and in other SEC filings. Sirna undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.
For further information, please contact: Howard W. Robin, President & CEO of Sirna Therapeutics, Inc., +1-303-449-6500; or Investors, E. Blair Schoeb, or Media, Justin Jackson, both of Burns McClellan, Inc., +1-212-213-0006, for Sirna Therapeutics, Inc.
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April 14, 2004
A Useful Analysis
There's an interesting article from two researchers in the International Clinical Psychopharmacology journal.
They've taken a look at the current research to discuss what what treatments are useful to those with Huntington's Disease. Here's what they recommend:
For movement disorders:riluzole, olanzapine & amantadine
For depression and various psychiatric issues:
selective serotonin reuptake inhibitors & mirtazapineFor 'optimal managment':
adjuvant psychotherapy, physiotherapy & speech therapyThe also discuss the possible usefulness of:
minocycline, unsaturated fatty acids & riluzoleHere's the abstract:
Int Clin Psychopharmacol. 2004 Mar;19(2):51-62.
Huntington's disease: present treatments and future therapeutic modalities.
Bonelli RM, Wenning GK, Kapfhammer HP.
University Clinic of Psychiatry, Karl-Franzens University Graz, Graz; University Clinic of Neurology, University of Innsbruck, Innsbruck, Austria. raphael.bonelli@klinikum-graz.at
Huntington's disease (HD) is a devastating neuropsychiatric disorder for which therapeutic interventions have been rather fruitless to date, except in a slight symptomatic relief. Even the discovery of the gene related to HD in 1993 has not effectively advanced treatments. This article is essentially a review of available double-blind, placebo-controlled trials of therapy for this condition which also includes relevant open label trials. Unfortunately, HD research has tended to concentrate on the motor aspects of the disorder, whereas the major problems are behavioural (e.g. dementia, depression, psychosis), and the chorea is often least relevant in terms of management. We conclude that there is definitely poor evidence in management of HD. The analysis of the 24 best studies fails to result in a treatment recommendation of clinical relevance. Based on data of open-label studies, or even case reports, we recommend riluzole, olanzapine and amantadine for the treatment of the movement disorders associated with HD, selective serotonin reuptake inhibitors and mirtazapine for the treatment of depression, and atypical antipsychotic drugs for HD psychosis and behavioural problems. Moreover, adjuvant psychotherapy, physiotherapy and speech therapy should be applied to supply the optimal management. Finally, some cellular mechanisms are discussed in this paper because they are essential for future neuroprotective modalities, such as minocycline, unsaturated fatty acids or riluzole.
PMID: 15076012 [PubMed - in process]
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April 07, 2004
DNA Research Getting Cheaper
FuturePundit has an excellent piece on the declining costs of DNA sequencing.
Simply put...lower costs means that there will be more genetic research done. In just two years the cost of mapping DNA Single Nucleotide Polymorphisms has dropped from 50 cents to 1 cent per. That's a real cost savings when you need to do 100,000 of them!
For genetic diseases such as Huntington's, this is just the kind of news we need to hear.
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March 22, 2004
Kenyon's Worms
The San Francisco Chronicle had an interesting article this past weekend that can be found on their website.
They discuss Kenyon's Worms, a genetically altered version of a common worm that lives much longer than it's unaltered kin. And they believe it has implications for the treatment of Huntington's Disease along with slowing down the aging process.
This is MANY years from being a viable therapy, but the article touches on a number of interesting genetic topics with mentions of HD. Check it out.
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February 10, 2004
Fast Cheap Way To Silence Genes
People with Huntington's Disease have one gene that makes a defective huntingtin protein and another gene that makes a 'good' huntington protein.
Suppose gene therapy could 'silence' (or stop) the one gene from creating the defective huntingtin protein? Scientists are working on this and other paths to treat Huntington's Disease with gene therapy. The cure is coming, but research takes time. But researchers are quickly getting better at speeding up research. Here's the latest, courtesy of Future Pundit:
"The group tested their approach by creating a handful of siRNA molecules to genetically disable three known genes. In each case, their technique generated siRNA that effectively blocked the gene in question."
"Wehrman said this technique of creating siRNA molecule libraries could be widely used to find genes that, when disabled, cause cells to become cancerous or alter how the cells respond to different drugs. These genes could then become potential targets for drugs to treat disease."
and
"Here is yet another reason why the rate of advance in biological research is accelerating. Better tools and techniques speed the rate at which experiments can be done and increase the amount of information that can be collected."
Read the Stanford Press Release here.
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February 05, 2004
A Giant Leap Forward
FuturePundit comes through with a great article on a fantastic development in genetic research. Scientists have come up with a new technique that allows them to study thousands of genes at once to determine if they are involved in a cell function.
This technique builds on the discovery of RNAi and will have a huge effect on future research. This could have a profound effect on the future of Huntington's Disease research. Here's an excerpt:
"With this high-throughput technology, however, we can study the function of a complete set of genes. We can systematically identify all the genes involving one process.
"The technique can be used to screen for genes involved in intercellular communication, cancer cell proliferation, and other cellular activity. Combined with drug screening the technique can accelerate the search for drugs that operate on particular cellular pathways and processes."
"...However, it would be possible to perform coordinated screens one for compounds that interfere with a target pathway and an RNA interference screen for genes that act in that pathway. This correlation would allow you to match the compounds with the proteins they affect in a much more useful way"
"...makes possible the faster rate of discoveries of disease causes and disease treatments. Cells are so complex with so many pieces, subsystems, and types of interactions that only with the development of massively parallel techniques can we hope to fully figure out how cells work and how to cure most diseases in the next few decades."
Folks...finding a treatment for Huntington's Disease involves understanding its effects on "cellular pathways and processes". This technique will also allow researchers to better identify what drugs are more effective. This is a big time saver.
Huge gains are being made...keep the faith!
Posted by Dave at 08:21 PM | Comments (0) | TrackBack
December 10, 2003
RNAi and microRNA
1993 not only was the year that the Huntington's Disease gene was found but it was also the year that microRNA was found. It's now the key to what may lead to a cure for Huntington's Disesase - RNAi or RNA interference.
Newsweek calls this one of the top 10 health stories of the year and it has the potential of being the health story of the decade. Here's a clip from this very interesting article:
"...because microRNAs are so small and simple in structure, they can be manufactured for use as research tools. If scientists suspect that a particular gene is responsible for a disease, they can design microRNA to silence the gene in affected laboratory animals. If the disease is prevented or cured, the gene becomes a target for treatment.
RNA interference has yet to generate new medicines, but if the technique fulfills its promise, it could help us treat everything from viral infections to cancer.
...Even so, a field that was just a curiosity in 1993 is now poised to change the worldall because we invested in basic research. The scientists who discovered microRNAs were not trying to prevent AIDS, grow stem cells or treat cancer. They just wanted to figure out how something happened in a worm. "
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October 05, 2003
Gene's On A Chip
This announcement doesn't have much effect on Huntington's Disease research but it is another significant step in the rapid progression of genetic research.
Affymetrix Inc. and Agilent Technologies have announce a new gene chip that fits portions of virtually the entire human genome onto a dime-sized chip. These chips are used in identifying genetic causes of genes. This is a far cry from what HD researcher's had to do in the 'old' days of genetic research - just a decade ago.
Here's an excerpt from the AP article:
"Researchers even envision a day when pediatricians and other physicians can be armed with the chips, technically called microarrays. The hope is that a drop of a newborn's blood can quickly be converted into a genome on a chip. From there, a doctor could determine the baby's predilection to disease and other genetic traits."
You can read the AP article here (and the original press release).
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August 24, 2003
Can We Get A Translator?
Here we report that Htt interacts with ND via HAP1, and that MLK2 phosphorylates and stimulates the activity of ND. Furthermore, we show that Htt and HAP1 facilitate the activation of ND by MLK2. To our knowledge, ND is the first example of a neuron-specific transcription factor involved in neuronal development and survival whose activity is modulated by Htt. We propose that Htt, together with HAP1, may function as a scaffold for the activation of ND by MLK2.
Huh??? When I started this blog
One of my goals was to provide readable explanations of what researchers, scientists, and doctors (the white coats) were saying. It aint easy. The English language, while vast, is inaccurate. To get around this limitation, white coats have developed their own language in order to talk to each other. The above excerpt is a good example.
When I saw this study abstract I knew I had a problem. It would take a small book to explain each of the terms used in the abstract, describe their relationship, and explain why this study is relatively important. So what am I going to do?
Skip to the conclusion
The University of Colorado study has provided some important clues on how the huntingtin protein (the protein affected by HD) is used in the building of brain cells. This type of research not only helps identify potential ways to treat Huntingtons Disease, it also provides information about neural cells that could benefit a wide range of neurological diseases and conditions (such as paralysis).
This study is another example of how money spent on HD research also advances research in so many other areas.
Heres the study abstract:
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9578-83.
Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2.Marcora E, Gowan K, Lee JE.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309, USA.
NeuroD (ND) is a basic helix-loop-helix transcription factor important for neuronal development and survival. By using a yeast two-hybrid screen, we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2), both of which are known to interact with huntingtin (Htt). Htt is a ubiquitous protein important for neuronal transcription, development, and survival, and loss of its function has been implicated in the pathogenesis of Huntington's disease, a neurodegenerative disorder. However, the mechanism by which Htt exerts its neuron-specific function at the molecular level is unknown. Here we report that Htt interacts with ND via HAP1, and that MLK2 phosphorylates and stimulates the activity of ND. Furthermore, we show that Htt and HAP1 facilitate the activation of ND by MLK2. To our knowledge, ND is the first example of a neuron-specific transcription factor involved in neuronal development and survival whose activity is modulated by Htt. We propose that Htt, together with HAP1, may function as a scaffold for the activation of ND by MLK2.
PMID: 12881483
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August 22, 2003
Have You Got A Hole In Your Head?
This has gotten some coverage but this article by ABC News is more reader friendly than most I've seen. Researchers are trying an experimental procedure in Parkinson's patients where they insert viruses (actually a safe virus segment) with a genetic code that will hopefully fix a genetic disease - gene therapy.
Because of the blood-brain barrier, they are inserting the virus through a small hole in the skull. Thus the 'hole in your head' mention. What they find out from this experiment will be closely followed by HD researchers who are also trying to deliver gene therapy to the brain.
You can read the article here.
Posted by Dave at 09:46 AM | Comments (0) | TrackBack
Genetic Research At UW
The Seattle Times today has an interesting interview with one of the leaders of the Human Genome project - Robert Waterston. From the article:
"Waterston, who turns 60 next month, came to the University of Washington in January to lead the department of genome sciences, which has three of the eight recognized leaders of the genome project. Last week, he broke ground on a $150 million state-of-the-art building to house his department and that of bioengineering."
You can read the article here.
Posted by Dave at 09:35 AM | Comments (0) | TrackBack
July 08, 2003
RNAi - Stop That Gene
Be sure to visit ScienCentral today and read their article on RNAi and treating Huntington's Disease. I have been excited about this technology since last fall when I stumbled across a press release from the University of Iowa.
Until now, a 'cure' for Huntington's Disease meant manipulating the DNA so that it no longer encoded such a long string of glutamine in the Huntingtin protein. Ten years after the discovery of the gene researchers are still working on a way of doing this effectively. That changed with the discovery of the RNAi process a couple of years ago. By using a process called RNA interference they don't change the DNA, they just block the 'bad' section, which codes the extra glutamine, from creating that bad portion of the Huntingtin protein. The result is the same as changing the DNA, only 'good' Huntingtin is produced. Best of all it's easy to do, at least when compared to editing DNA. Already it is greatly speeding up (by as much as a factor of 10) many area's of DNA-related research and researchers have 'cured' many diseases in mice and in test tubes.
The discovery of RNAi is expected to produce one or two Nobel prizes within the next few years and it offers the possibility of curing a host of diseases. I believe it will eventually go down as one of the most important medical discoveries in the last 100 years. You'll be reading a lot about on the HD Blog.
The article discusses specific issues in using RNAi to treat Huntington's disease and there is an excellent video on how the process works. Also, I don't believe it's clearly mentioned here, it's already been determined that RNAi can distinguish between a 'good' huntington gene and a 'bad' one ensuring that only the bad gene is targeted. If they can find a way to deliver this gene through the blood-brain barrier without invasive surgery (such as with a disabled virus or virus segment) it could become available within a very short period time (within the next few years). The same technique, but different target gene, would cure many diseases that are considered common or well known today. It's theorized that many viral diseases such as AIDS could be cured with RNAi targeting the virus DNA.
Posted by Dave at 03:10 PM | TrackBack
July 03, 2003
Ethics and Genetics
There is little doubt that a true cure for Huntington's Disease is going to come from genetic research. After all, its a genetic disease. That doesn't mean that an effective treatment can't come from some other area of medical research but "The Cure" will require the hard work many genetic scientists.
Because of this we tend to glance over news that is critical of some genetic research. After all who wants to be critical of that which might save us? It's true that much of the criticism is unwarranted. For example, some critics obviously spent too much time in their youth watching old 50's horror films. They make scary claims about genetic research and coin terms such as "Frankenfood". The result of this hysteria is death. Malnutrition is killing millions of people in the third world while needed (and safe) food and seed stays in warehouses and on docks.
Just because the industry is the target of unwarranted criticism doesn't mean there aren't areas of concern. Genetics is the new "gold rush". Billions of dollars can be made from important discoveries. This economic incentive has caused a flood of interest and investment into genetic research. One of the reasons the Human Genome Project was finished early was the private sector funding their own research in hopes of garnering valuable patents. Each wise investment brings us one step closer to finally getting cures for genetic diseases.
The motivations for advancing research aren't just financial. A scientist who makes a dramatic breakthrough can earn fame in the scientific community and even in society at large. (Who hasn't heard of Madame Curie for example?) In addition a scientist can also benefit financial, if not from patents, from funded 'chairs' at universities, lecture fees, and books. And of course there is the Holy Grail of research - the Nobel Prize.
In any 'gold rush' environment short cuts are taken by some to gain an edge. While the vast majority of genetic scientists are ethical and are doing careful research, there are a dangerous few who take ethic short cuts in order to gain an edge. Unfortunately, those who would benefit the most from good research are also the ones who hurt the most by bad research.
There are two ways bad research hurts us all. First, it creates a bad impression of genetic research among the public and politicians. This has the tendency to reduce the amount of money flowing into research and increases costs & development time due to additional regulation and oversight. Second, bad research siphons off money that would have been spent on more valuable genetic research. After all, there are only so many research dollars out there to be had.
It's important that those of us in the HD community be vigilant against bad genetic research. Ultimately, this bad research delays the day when we will finally hear that a cure has been developed and that delay will be at the cost of the lives of some of our friends and family.
In case youre wondering why I wrote this rant today, here are two articles just published in the UKs The Guardian newspaper: ">Scientists hit out at the creator of she-males & Playing God (Warning: This will be disturbing for some of you.)
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