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Mike, of the potential collaborators who would you like to see working with the company? There are many who would not, and some who would not offer much (IMO).
Mike, that answers the question and I am sure that the company (who do apparently monitor these boards) will take note.
Mike, let me refer you back to this post where I looked at the possible categories. Which ones do you like, and why would say 8 be so inferior to another "arbitrary" number such as 16?
http://www.investorshub.com/boards/read_msg.asp?message_id=1837734
Mike, what categories would you like to see?
I will leave others to find negatives in the newsletter. I believe that it actually contains one very fundamental insight:
"Genealogists are not as interested in a person’s eye color or hair color as the forensics community or the police. Similarly, police are not interested in a person’s genetic heritage or family tree. In the pharmaceutical development industry, however, we are interested in both, and in other markers hidden in the complex human gene code."
One of the questions I put into the shareholders meeting list was:
"Do AIMs related to pigmentation genes have any special significance in drug metabolism and associated pharmacogenomic classifiers?"
I believe that the answer to this question is yes they do have a special significance, which can be inferred from study of the patent applications, and that this is alluded to above. I wonder what exactly the "other markers" referred to above will turn out to be.
DNA testing topic at American Indian Center
http://www.semissourian.com/story.html$rec=140773
The topic of discussion for the July 10 American Indian Center of the Heartland meeting will be how to prove an American Indian blood line through DNA testing. The meeting will be held at 4 p.m at the center, 811 Broadway, Cape Girardeau. Call 334-4929 for more information.
I know of one way...
Prescription for trouble
http://www.technologyreview.com/articles/wo_jonietz070104.asp?trk=nl
British regulators say it's now OK to buy potent cholesterol-busting drugs without a prescription, but medical experts wonder if such easy access is a good idea.
By Erika Jonietz
July 1, 2004
Starting this month, British consumers will be able to buy a powerful, cholesterol-lowering drug without a doctor’s prescription. The U.K. government has billed the move, the first time a member of the class of drugs known as statins has been available over-the-counter, as a boon to public health, sure to help prevent Britain's number one killer: heart disease. But within days of the May 13 announcement, doctors began vocal criticism of the decision, raising doubts about both the safety of and motivations behind it. And a similar step by the U.S. Food and Drug Administration seems inevitable, as drug companies are for the third time requesting permission to sell two different statins without prescriptions.
In a press release announcing the approval of the nonprescription sale of simvastatin, sold by Merck as Zocor, British Health Secretary John Reid noted that the Committee on Safety of Medicines had concluded the benefits of the shift outweighed the risk. “This new move will allow more people to protect themselves from the risk of coronary heart disease and heart attacks,” he said.
But a May 22 editorial in the British medical journal The Lancet said the decision to allow over-the-counter sales of the drug was made with little evidence on either the safety or efficacy of offering it to the public without physician monitoring. The U.K. Department of Health, the journal said, was turning the population into “guinea pigs in this large-scale OTC experiment.” The British Medical Association has publicly questioned not only the wisdom of the move but also the motives behind it, saying that the government is attempting to shift the cost of heart disease prevention from the National Health Service onto individual patients.
The decision and its outcome are being closely watched in the United States. Last November, reports surfaced that Merck was planning to ask the FDA to review Mevacor, the first statin sold and now off-patent, for OTC status. In 1997 and again in 2000 the FDA had rejected over-the-counter marketing applications from Merck for Mevacor and Bristol-Myers Squibb for Pravachol, another related statin, citing safety concerns. But the agency has softened its position: in 1997, regulators called all statins unsuitable for over-the-counter sale. Although the agency again rejected OTC sales of the statins in 2000, it withdrew that statement, leaving what some see as an opening for future approval.
“I do think eventually we’ll have over-the-counter statins,” says Joshua P. Cohen of the Tufts Center for the Study of Drug Development; Cohen is an expert in switches of drugs from prescription to over-the-counter status. But, he cautions, there are concerns over efficacy, safety, and cost.
While statins do effectively lower cholesterol, they can't simply be taken like antacids or allergy medications. For one thing, the same dose won’t work for everyone. And unlike allergy or pain medication, where symptom relief is clear, “cholesterol levels are not an easily diagnosed condition,” says Cohen, leaving open the question of how patients taking the drug without a doctor’s supervision will know what’s best for them.
A study published in the April 8 New England Journal of Medicine, for example, found that patients who received high doses of statins had 16 percent fewer cardiovascular events than a control group. But the British government approved only the lowest dose of simvastatin—10 milligrams—for over-the-counter sale. In fact, prescription data from health data company IMS Health suggests that fewer than 30 percent of simvastatin prescriptions in Britain are for the 10-milligram dose; most simvastatin patients take 20 milligrams, and more than 25 percent take 40 milligrams. Doctors worry that without regular monitoring, patients may not find the right dose to affect their cholesterol levels.
Side effects are also a concern. Doctors routinely monitor patients taking statins for liver damage. And 31 patients taking the statin Baycol died from rhabdomyolysis, a rare but dangerous muscle breakdown that can lead to kidney and other organ damage; these deaths led to Baycol’s recall in 2001. “You certainly don’t want people taking an over-the-counter medication and dying from it,” says Cohen. “I wouldn’t be too alarmist about it, but that’s a real concern.”
Doctors also worry about harmful interactions with drugs heart patients may already be taking, including other cholesterol-lowering drugs, anticoagulants, antifungals, and even common antibiotics. This could be a bigger problem in the United States than in Britain, where simvastatin will actually be sold in a special class of over-the-counter drugs for which pharmacists act as gatekeepers. Although a cholesterol test will not be required, patients will have to answer questions to allow pharmacists to determine their risk of coronary heart disease, as well as what other drugs they are taking. But the advent of such a system doesn’t seem likely in the United States. There is a small fee for pharmacist counseling in Britain, and U.S. patients won’t want to pay for it, says Peter Jones, codirector of the Lipid Metabolism and Atherosclerosis Clinic at Baylor College of Medicine in Houston. “If I’ve got a $10 copay to see my doctor, why should I pay $10 for the pharmacist to tell me this when I maybe trust my doctor better?” he asks. “I don’t think the U.S. is ready to have that tier.”
Still, most experts feel that risks of adverse effects are small. Of more concern is that patients will lose the chance for more comprehensive counseling from their doctors on risk factors such as diet, exercise, weight, and smoking. "Some people feel that taking a Lipitor [statin] and eating a Big Mac at the same time is somehow going to offset one another," says Cohen. "And you wouldn't want that to happen on a large scale."
Perhaps the major objection of British doctors, though, is cost, says Cohen. About 1.8 million Britons currently have prescriptions for statins, costing the National Health Service more than $1.2 billion a year; that figure is predicted to grow to more than $3.6 billion a year by 2010. Doctors worry that many patients who currently receive the drugs for free will be unable to afford the predicted monthly cost of roughly $18 to $27 for a drug usually taken for years.
Even in the United States, where most patients already pay for at least part of their prescriptions, cost could be a problem, according to Cohen. “These are daily medications,” he says. “It can be anywhere between $20 and $60 a month or more, maybe $100 a month.” Insurance companies might follow the model seen recently with allergy medications, taking newer, more expensive statins off the list of covered drugs if an older statin becomes available over the counter—in effect, shifting the cost of the drugs to consumers.
But despite the risks and costs, many believe over-the-counter statin sales would have benefits in helping to prevent coronary heart disease. Wider availability of the drugs could, for instance, help shift consumer spending away from “nutraceuticals,” over-the-counter supplements with questionable health benefits. Says Jones: “There are people who would spend the same amount of money as you can spend on a statin taking garlic pills, which do absolutely nothing.”
Allowing over-the-counter sales of statin drugs could increase their use, ultimately helping a huge number of people. “Anyone with risk beyond the most trivial level will, somewhere around the age of 50 or 60, see the benefit of a statin far outweigh the risks,” says cardiologist Richard A. Stein, associate chair of medicine at the Singer Hospital of Beth Israel Medical Center in New York and a spokesperson for the American Heart Association. Less than one-third of Americans with elevated cholesterol are being treated, according to the association. “The current model is leaving untouched and at high risk a substantial amount of our population,” Stein says. Buying a statin drug in the drug store “isn’t a good alternative to seeing a physician,” Stein emphasizes. But he believes that there are large numbers of people who don’t get into the medical system and whose risk of heart disease and heart attack would be reduced if they took the pill. “Since it’s the major cause of death and disability in the United States, a 10 percent reduction in that risk is extraordinary in terms of its health care implications.”
An FDA decision to give statins over-the-counter status in the United States could come within the year—or not for several years. In the meantime, experts say, they’ll be closely watching how things go on the other side of the Atlantic. “In Britain we’ll have a nice test model,” says Stein. “We’ll be able to look at, five years down the road, how widely it’s used, what’s happening to the overall risk of heart attacks, and we’ll have a very nice model to see if it works.” To their benefit or not, it seems that British consumers will indeed be serving as test subjects in a massive medical experiment.
Ethnic differences in P450s and drug transporters
This one is a bit heavy:
http://www.jssx.org/dmpk/d192/dmpk192083.pdf
Chemotherapy regimen more effective and more toxic in Japanese patients than in American patients
http://www.news-medical.net/?id=2255
Posted By: News-Medical in Pharmaceutical News
Published: Monday, 7-Jun-2004
A chemotherapy regimen commonly used to treat non-small cell lung cancer is both more effective and more toxic in Japanese patients than in American patients, researchers reported Saturday at the annual meeting of the American Society of Clinical Oncologists. The first of its kind, this analysis underscores the importance of genetic variations in medicine and points to a need for increased international collaboration in trials of new cancer treatments.
“Results of a cancer clinical trial performed in one part of the world may not necessarily hold true for populations in other regions,” said lead investigator David Gandara, director of clinical research at UC Davis Cancer Center and professor of medicine at the UC Davis School of Medicine. “We need to be cautious when we extrapolate from one population to another.”
The analysis compared results from two phase III clinical trials designed to evaluate the relative effectiveness of various treatments for patients with advanced non-small cell lung cancer. One trial was conducted in the United States, the other in Japan. The two trials were carefully structured from the outset, through a lengthy series of meetings between U.S. and Japanese investigators and representatives of the Japanese Ministry of Health, to have a “common arm.” The approach allowed researchers to make direct comparisons of one chemotherapy regimen — paclitaxel and carboplatin — in both populations. Patients in both trials were closely matched in terms of age, gender, disease stage and tumor type.
The collaboration is the first to prospectively design a “common arm” in a U.S. cooperative group trial and in one conducted in another country.
Median survival time was 12 months for the Japanese patients in the paclitaxel-carboplatin arm of the study, versus nine months for U.S. patients receiving the same regimen. Half of the Japanese patients (51 percent) survived one year, versus only slightly more than a third (37 percent) of the American patients.
“The reasons for the increased survival among the Japanese patients remain to be determined, but the implications of this observation are of considerable interest,” Gandara said.
The longer survival in the Japanese group was especially striking because those patients had to be given a lower dose of paclitaxel due to toxicity. Even with the lower dose, the Japanese patients were able to complete fewer cycles of the chemotherapy regimen, and some side effects were more severe.
The U.S. patients received 225-milligram doses of paclitaxel; the Japanese patients received 200-milligram doses. Earlier phase I studies of paclitaxel in the U.S. and Japan set these as the maximum tolerated doses for each population.
Despite the reduced dose, only one in four of the Japanese patients (24 percent) completed three cycles of the paclitaxel-carboplatin regimen, versus 100 percent of the U.S. patients. And only about one in 10 Japanese patients (11 percent) completed six cycles, versus more than a third of the U.S. patients (36.5 percent).
Neutropenia, in which levels of infection-fighting white blood cells drop to dangerous levels, was more than twice as common in the Japanese patients. Neutropenia accompanied by fever was more than five times as common in the Japanese patients.
On the other hand, one side effect, neuropathy, was more common in the U.S. patients, for good reason, according to Gandara. Neuropathy results from cumulative exposure to many cycles of paclitaxel, and the U.S. patients completed more cycles. Neuropathy is characterized by tingling, numbness or pain due to nerve damage.
Patients in both trials received equivalent levels of carboplatin.
Gandara and his colleagues believe the differences between the U.S. and Japanese patients are likely due to genetic differences in drug metabolism, an area of science known as pharmacogenomics. Recent research has identified specific genes involved in paclitaxel metabolism, and these genes may prove different from one ethnic group to another.
“These findings underscore both the importance of global clinical trials, and the importance of ensuring that we do them carefully. It will be critical to take into account possible pharmacogenomic differences among populations as we move toward global trials,” Gandara said.
The U.S. trial was conducted through the Southwest Oncology Group, one of the country’s largest National Cancer Institute-sponsored cancer clinical trials cooperative groups, comprising 283 institutions in the United States and Canada.
The Japanese study was conducted through the FACS group, or Four-Arm Comparative Study Group.
The combination of paclitaxel and carboplatin is commonly used to treat non-small cell lung cancer in the U.S., but had never been studied in a large clinical trial in Japan.
While major pharmaceutical companies have conducted global trials of investigational drugs, there is no mechanism at present to conduct joint NCI-sponsored trials internationally. “We hope this analysis will serve as a model for future prospective comparisons of cooperative group trials,” Gandara said.
http://www.ucdmc.ucdavis.edu
What were the stars like when you were young?
They went on forever. They... When I... We lived in Arizona, and the skies always had these little fluffy clouds in them. And they were long, clear, and there were lots of stars at night. And when it would rain, they would all turn – they were beautiful, the most beautiful skies, as a matter of fact. Um, the sunsets were purple and red and yellow and on fire, and the clouds would catch the colors everywhere. That's, uh, neat cause I used to look at them all the time when I was little. You don't see that. You might still see it in the desert.
Robert, the Universe has replied - with vigor! I must admit I had a good laugh when I saw the press release this morning.
bag8ger, barking up the wrong tree IMO.
BBBabe, I worked in the financial industry for many years. I can reliably inform you that it was corrupt then, and can reasonably infer that it is still corrupt now. Unless and until you have honest regulators equipped with legislation with teeth AND the will to effect reform (however painful and no matter what vested interests are "disadvantaged") then we will always have the current status quo. There have been some promising developments recently but they do not IMHO go anywhere near far enough.
Robert, that is the real crux of the issue - are the AIMs mentioned by various researchers the same AIMs that we have filed patent on, and is the researcher's awareness of them (and the term "ancestry informative markers") through the company or just through Mark Shriver. Some people are clearly trying to find their own AIMs (whether they refer to them as such or use another term). Others seem to be using a subset of the AIMs used by DNAP (you see various total number of AIMs mentioned in different pieces of research). Some people might be using ADMIXMAP (our platform, not LSHTM's program with the same name). We could not tell from the literature that work with Moffitt was on-going until it was publicly announced. Overall, we do not know the relative numbers of researchers involved. I agree with you though it is encouraging to see the approach and the terminology being increasingly utilized by a number of different research groups, hopefully resulting in mainstream technology which we just happen to hold the patent on.
stakddek, the Berlin exchange was also included in the questions submitted for the shareholders meeting:
10.a) Can the company confirm that it has applied to be delisted from the Berlin Exchange and also confirm the status of the listing on the Frankfurt Exchange? Does the company have plans to list on other foreign exchanges?
10.b) Has the company considered possible courses of action to address potential naked short-selling of its stock? These could include delisting from exchanges, removing its stock from the DTCC system and issuing physical certificates, and recalling all of its stock and re-issuing it to shareholders of record.
DNA Fingerprinting and Civil Liberties Project
May 14 - 15 2004
Harvard University, Kennedy School of Government
http://www.aslme.org/media/list_programs.php?conf_id_sel=51
DNAP and the LA case are mentioned in this presentation:
http://www.aslme.org/media/list_speaker.php?speech_id=177#
DNAP are also mentioned in this one:
http://www.aslme.org/media/list_speaker_basic.php?speaker_id=119
Continent-of-origin admixture studies
http://www.getcited.org/pub/103403801
CONTRIBUTORS: Author: Sweet, Frank W. (University of Florida)
CONFERENCE NAME: Fifth Union, The Melungeon Gathering
CONF. LOCATION: Kingsport, TN
CONFERENCE YEAR: 2004
PUB TYPE: Conference Presentation
SUBJECT(S): Continent-of-origin admixture studies using ancestry-informative markers in autosomal DNA
DISCIPLINE: History
HTTP: http://www.melungeons.com/union/fifthunion.htm
LANGUAGE: English
PUB ID: 103-403-801 (Last edited on 2004/06/20 05:01:56 GMT-6)
SPONSOR(S):
ABSTRACT:
One possible explanation for the high present incidence of sub-Saharan DNA in White Americans (1/3 have 2-20% African admixture) is a relatively high but unnoticed rate of families passing through the color line from Black to White during the 18th and 19th centuries. The triracial isolate communities of the Southeast may have served as a buffer zone or halfway house facilitating such color-line permeability.
The genetics of beauty
http://enjoyment.independent.co.uk/books/reviews/story.jsp?story=533914
Mutants by Armand Marie Leroi
Being normal is quite incredible, really
22 June 2004
Armand Leroi is not yet a household name but he soon will be, if Mutants wins the following it deserves. The discovery of a distinguished scientist who can write with such flair and style is cause for rejoicing.
It's not easy to make developmental biology - the mysteries of the embryo's progression from single cell to new-born baby - into a riveting read. But Leroi manages to inform and intrigue, by turns. In places, his book, and the three-part Channel 4 documentary that accompanied it, are downright gruesome. Leroi's approach is to describe, in hideous detail, the deformities of development that afflict the human form.
He concentrates on historical examples, and the myths they perhaps inspired: the cyclops, mermaids, hermaphrodites, dwarfs and giants. A huge cast of afflicted humanity, variously feted in royal courts, consigned to fairground freak-shows, and dissected and displayed by scientists and medics, is relentlessly catalogued. Leroi's mission is to make us realise how incredible it is that most of us are born with the usual number of heads, limbs, fingers and toes.
He vividly conveys the wonderment of embryos as self-organising entities, which - like sci-fi aliens - invade women's bodies and take root there. A scientist with an evolutionary perspective, he's also keen to stress the commonalities between us and other animals, and his focus is on the genes shared between salamanders, mice and men.
Mutants - genetic mistakes - fascinate because of what they reveal about the logic of an embryo's self-assembly plan. To date, researchers have pinpointed a few dozen genes that control key developmental pathways. Leroi refreshingly rejects the usual metaphors of linear hierarchies of command, and talks, instead, of "a reciprocal flow of information as precarious as the flow of batons between two jugglers standing at opposite ends of a stage". But each refinement of a developing toe or hair follicle requires "subtle negotiations, the nature of which we scarcely understand".
The TV series of Mutants was powerful, but the book is better. The author does not intrude; this is no memoir of exploits in the laboratory. What's more, against convention, Leroi largely resists the temptation to pronounce on bioethical matters.
Contentiously, he reveals what he would like to know more about. "Racial" differences - the tiny fraction of the global genetic variation that distinguishes people in different parts of the world - fascinates him. The search for gene variants known as Aims, or "Ancestry Informative Markers", is already well under way. Second on his wish-list is the genetics of beauty. If mutations give us misaligned teeth, graceless noses and asymmetrical ears, perhaps the true meaning of beauty is "the relative absence of genetic error".
Leroi remains sanguine, as "Reasonable people know that the differences among humans are so slight that they cannot be used to undermine any conceivable commitment to social justice". Watch this space; Leroi must surely venture again into the perilous waters of media science.
Admixture in Brazil
http://www.scielo.br/scielo.php?script=sci_abstract&pid=S0103-40142004000100004&lng=en&n...
PENA, Sérgio D.J. and BORTOLINI, Maria Cátira. Pode a genética definir quem deve se beneficiar das cotas universitárias e demais ações afirmativas?. Estud. av., 2004, vol.18, no.50, p.31-50. ISSN 0103-4014.
IN THIS ARTICLE we used tools of molecular and population genetics to estimate quantitatively the African contribution for the formation of the Brazilian population. We examined two genomic compartments: mitochondrial DNA (mtDNA), maternally inherited, and nuclear DNA, inherited from both parents. The studies using mtDNA showed that about 30% of Brazilians self-classified as White and 80% of Brazilian Negroes carry maternal lineages typical of Sub-Saharan Africa. Using these data we could estimate that at least 89 million Brazilians are afrodescendants, a number considerably larger than the 76 million individuals self-classified as Negro in the 2000 census. The analyses on nuclear polymorphisms employed "ancestry informative" markers and showed even more striking results. On the basis of studies in individuals self-classified as White from several Brazilian regions, we estimated that approximately 146 million Brazilians (86% of the population) had more than 10% African contribution to their genome. These numbers should be taken into account in discussing affirmative action programs in Brazil, but in a descriptive rather than a prescriptive sense.
Cosmic, I find the prospect of the general population being able to purchase Statins over the counter to be quite disturbing. Time for a rethink on this perhaps...
Remember Jose Fernandez?
Gower BA, Fernandez JR, Beasley TM, Shriver MD, Goran MI. Using genetic admixture to explain racial differences in insulin-related phenotypes. Diabetes. 2003 Apr;52(4):1047-51.
Fernandez JR, Shriver MD, Beasley TM, Rafla-Demetrious N, Parra E, Albu J, Nicklas B, Ryan AS, McKeigue PM, Hoggart CL, Weinsier RL, Allison DB. Association of African genetic admixture with resting metabolic rate and obesity among women. Obes Res. 2003 Jul;11(7):904-11.
Bonilla C, Shriver MD, Parra EJ, Jones A, Fernandez JR. Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city. Hum Genet. 2004 Jun;115(1):57-68.
Here is a new NIH grant:
Grant Number: 1R01DK067426-01
PI Name: FERNANDEZ, JOSE R.
PI Email: jose@uab.edu
Project Title: Admixture Mapping for Insulin Complex Outcomes
Abstract: DESCRIPTION (provided by applicant): Racial and ethnic differences in the incidence of diabetes have been identified in epidemiological studies. Although recent investigations have associated genetic markers and environmental factors contributing to the diabetes-related phenotypes within populations, the extent to which these factors in fact account for racial/ethnic differences is still unclear. The main objective of this study is to investigate the effect of genetic and environmental parameters on racial/ethnic differences in diabetes-related traits by modeling individual estimates of genetic admixture and environmental measures of energy intake, energy expenditure and socioeconomic status (SES) on measures of fasting insulin, sensitivity to insulin and initial phase of insulin secretion after exposure to glucose. A sample of 120 African-American (AA), 120 European-American (EA) and 120 Hispanic-American (HA) boys and girls of 7-13 years of age will be tested to obtain outcomes of insulin action and response, body composition, energy intake and energy expenditure to questionnaire and SES. The specific aims of this investigation are: (a) To test the role of European genetic admixture on diabetes-related measures of fasting insulin (FI), insulin sensitivity (Si) and insulin response to glucose (AIRg) after adjusted for body composition parameters (2) To investigate how the relationship between the environmental parameters energy intake, energy expenditure and socioeconomic status differ as a function of admixture and diabetes-related measures of fasting insulin (FI), insulin sensitivity (Si) and insulin response to glucose (AIRg), and (3) To test phenotype-genotype associations between ancestry-informative markers (AIMs) and measures of FG, Si and AIRg after adjusted for body composition and environmental parameters in a sample of AA, HA and EA prepubertal children. The proposed investigation will provide meaningful and important insight into the understanding of biological, non-biological and the interaction of both components in racial/ethnic differences in diabetes-related traits. Furthermore, the results of this investigation will serve as a tool for the development of effective preventive strategies to reduce the prevalence of diabetes and its related traits in racial/ethnic populations.
Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM
UAB STATION
BIRMINGHAM, AL 35294
Fiscal Year: 2004
Department: NUTRITION SCIENCES
Project Start: 01-JUL-2004
Project End: 30-APR-2009
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
IRG: NTN
Call to ban anti-cholesterol drug
http://news.bbc.co.uk/2/hi/health/3838915.stm
One of the newest cholesterol-lowering drugs should be removed from the market because of safety concerns, an expert has said.
Dr Sidney Wolfe from US consumer group Public Citizen says the statin Crestor (rosuvastatin) carries a higher risk of side effects than other statins.
Writing in the Lancet, he says the risk of muscle wastage and kidney failure means the other statins should be used.
Manufacturer AstraZeneca says Crestor is as safe as other statins.
Statin medicines have been available in the UK for the last 14 years.
There are five different types available, including rosuvastatin, licensed for use in the UK by the government's Medicines and Healthcare products Regulatory Agency.
All statins work to lower cholesterol which, in turn, reduces the risk of cardiovascular disease - the biggest cause of death in the UK.
Rosuvastatin was launched last year in the UK and about 110,000 patients had received the drug by March 2004.
In May this year, rosuvastatin's manufacturer AstraZeneca sent a letter to doctors reminding them to reserve the highest doses for patients at highest risk of heart disease because of safety concerns.
Safety concerns
The concern was about the drug's link with a condition called rhabdomyolysis - a muscle wasting condition that can lead to kidney damage and failure.
Other statins also carry a risk of rhabdomyolysis and kidney failure, which is dose related.
The government's Committee on Safety of Medicines monitors these side effects.
It says about one case report of rhabdomyolysis has been received for every 100,000 patients, for each year of treatment with any statin.
A detailed analysis by the CSM and MHRA of the safety information for rosuvastatin at the end of its first year suggested that although the top (40mg) dose benefits a small percentage of patients, it may be associated with a higher rate of side effects, including rhabdomyolysis.
The CSM received six reports of suspected rhabdomyolysis associated with rosuvastatin. Five of these were receiving the maximum 40mg dose.
But Dr Sidney Wolfe is worried that even the lowest dose, 10mg, carries too high a risk.
He says the US has seen 20 cases of rhabdomyolysis and kidney failure in people taking 10mg of the drug.
"The renal toxicity, high rate of cases of rhabdomyolysis compared with other statins, and lack of unique benefit are compelling reasons to remove rosuvastatin from the market before additional patients are injured or killed," he says in his letter.
Dr Jim Kennedy, prescribing spokesperson for the Royal College of General Practitioners, said: "The reported incidents of the side effects of rhabdomyolysis and kidney damage with this drug are of concern and we need a clear assessment and advice from the licensing authorities [such as the CSM] on the safety and efficacy of this drug."
The CSM said: "As with other new medicines, the safety of rosuvastatin will continue to be closely monitored by the Medicines and Healthcare products Regulatory Agency and CSM.
"Should any new information or concerns regarding the safety of rosuvastatin emerge, the CSM and MHRA would take all necessary regulatory action.
AstraZeneca said Dr Wolfe's claims were "misleading" and based on inappropriate interpretation of data.
Dr Neil Brickel, the company's UK physician for Crestor, said Dr Wolfe had failed to look compare the number of cases with side effects with the rate of the drug used.
"The rate of side effects with Crestor is completely in line with other statins. Ten milligrams has been associated with some cases of rhabdomyolysis, but so has 10mg of the other statins as well.
"We are talking about a very rare side effect. The benefit-risk profile of Crestor is far in favour of benefit," he said.
Over-the-counter concerns
The warning intensifies doctor's concerns about patients soon being allowed to buy statins at pharmacies "over-the-counter" without the need of a prescription.
The British Medical Association is concerned about the safety and efficacy of statins being available over-the-counter.
From next month, another type of statin, simvastatin will be available over-the-counter as well as on prescription.
Dr John Chisholm, chairman of the BMA's General Practitioners Committee, said: "We are concerned that there won't have been a sufficiently thorough risk assessment before the drug is purchased.
"There are concerns about the risks of treatment as there are potential side-effects with all statins. Patients taking statins should be monitored on a regular basis to assess the effectiveness of the treatment."
You're assuming I haven't blotted my copybook with the company frog (as at least one devout long has lol)! There is no need for me to resend it for the purpose stated. I suggest we wait and see what happens at the shareholder meeting. The company would hardly not respond due to your posting record. If you were tdiamonds however...
Queensland University has come up before as well:
http://www.investorshub.com/boards/read_msg.asp?message_id=2081647
W2P referred to this work earlier on RB:
http://www.investorshub.com/boards/read_msg.asp?message_id=2082102
Greg Barsh is also involved in this area:
http://www.hhmi.org/research/investigators/barsh.html
You can see from this presentation at Stanford that he is familiar with the work of both DNAP and Rick Sturm:
http://hgjc.stanford.edu/past_presentations.html
5/25/04 Greg Barsh Crypts, Furrows, and Twins: Genetics of Eye Color
Frudakis T et al. Sequences associated with human iris pigmentation. Genetics. 2003 Dec;165(4):2071-83.
Duffy DL et al. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum Mol Genet. 2004 Feb 15;13(4):447-61. Epub 2004 Jan
Larsson M et al. Importance of genetic effects for characteristics of the human iris. Twin Res. 2003 Jun;6(3):192-200.
Here is a more recent paper by Rick Sturm:
Zhu G, Evans DM, Duffy DL, Montgomery GW, Medland SE, Gillespie NA, Ewen KR, Jewell M, Liew YW, Hayward NK, Sturm RA, Trent JM, Martin NG. A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res. 2004 Apr;7(2):197-210.
Queensland Institute of Medical Research, Brisbane, Australia.
We have rated eye color on a 3-point scale (1 = blue/grey, 2 = hazel/green, 3 = brown) in 502 twin families and carried out a 5-10 cM genome scan (400-757 markers). We analyzed eye color as a threshold trait and performed multipoint sib pair linkage analysis using variance components analysis in Mx. A lod of 19.2 was found at the marker D15S1002, less than 1 cM from OCA2, which has been previously implicated in eye color variation. We estimate that 74% of variance in eye color liability is due to this QTL and a further 18% due to polygenic effects. However, a large shoulder on this peak suggests that other loci affecting eye color may be telomeric of OCA2 and inflating the QTL estimate. No other peaks reached genome-wide significance, although lods > 2 were seen on 5p and 14q and lods >1 were additionally seen on chromosomes 2, 3, 6, 7, 8, 9, 17 and 18. Most of these secondary peaks were reduced or eliminated when we repeated the scan as a two locus analysis with the 15q linkage included, although this does not necessarily exclude them as false positives. We also estimated the interaction between the 15q QTL and the other marker locus but there was only minor evidence for additive x additive epistasis. Elaborating the analysis to the full two-locus model including non-additive main effects and interactions did not strengthen the evidence for epistasis. We conclude that most variation in eye color in Europeans is due to polymorphism in OCA2 but that there may be modifiers at several other loci.
Great find (again) by 4titudinous. Some background:
http://www.investorshub.com/boards/read_msg.asp?message_id=2582248
http://www.investorshub.com/boards/read_msg.asp?message_id=2489949
http://www.investorshub.com/boards/read_msg.asp?message_id=2206475
http://www.investorshub.com/boards/read_msg.asp?message_id=1718560
Another example of MALD at Harvard
Grant Number: 1R01NS046630-01A1
PI Name: REICH, DAVID E.
PI Email: reich@receptor.med.harvard.edu
PI Title:
Project Title: A Whole Genome Admixture Scan for Multiple Sclerosis
Abstract: DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is an inflammatory disease of the CNS. It is thought that tissue injury occurs when activated, myelin-reactive T cells migrate into the CNS and cause damage to myelin, oligodendrocytes and axons. Ultimately, MS is a complex genetic disease as studies in twins, half-siblings, and adoptees indicate a strong family inheritability. However, large-scale studies attempting to identify genes affecting the disease have so far had limited success, calling for a more powerful search strategy. The classic method of finding genes--linkage mapping--works well for rare, single gene disorders that run simply in families. But linkage scans have failed to find the genes for more common, genetically complex diseases including MS. The approach most likely to work for gene discovery is the direct assessment of variation in populations and its association to disease. With present technology, the best-known way of doing this---haplotype mapping--is not practical because it requires studying too many sites in the genome. Because MS is significantly more common in Europeans than in Africans, a new approach, admixture mapping, may be a shortcut for using association studies to find disease genes. Specifically, we hypothesize that the intermediate genetic risk of MS in African Americans is derived almost entirely from their small percentage (10-40%) of European ancestry. By scanning along the genomes of African Americans with MS looking for regions of unusually high European ancestry, we can identify the 'European' gene segments that are likely to contain the genes that are related to MS risk. In this study, we propose to carry out the first whole-genome admixture scan for human disease genes, using 100-times fewer markers than a haplotype-based study. An admixture scan has the potential to rapidly identify disease regions especially for the subset of diseases that have different prevalences in two populations. The admixture mapping approach has only become feasible in the past year because of the large numbers of SNPs discovered with known frequencies in both African- and European-Americans. The SNP resources and novel analytical tools have now converged with large sample collections of African-American MS patients. The central aim of this project will be to carry out an admixture scan for MS genes in a sample of 1,000 African Americans with MS and 340well-matched controls. To follow-up all the genomic regions associated with disease, we will triple density of markers to increase statistical confidence in the results and refine the positions. We will then move to a targeted haplotype-based association study in the most interesting regions to clone new genes associated with MS.
Thesaurus Terms: biomarker, diagnosis design /evaluation, genetic mapping, genetic screening, multiple sclerosis, single nucleotide polymorphism computer program /software, early diagnosis, molecular cloning, racial /ethnic difference African American, clinical research, human genetic material tag, human tissue
Institution: HARVARD UNIVERSITY (MEDICAL SCHOOL)
MEDICAL SCHOOL CAMPUS
BOSTON, MA 02115
Fiscal Year: 2004
Department: GENETICS
Project Start: 15-JUN-2004
Project End: 31-MAR-2009
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: IMS
You are most welcome! eom
Frog, not being born yesterday I am familiar with the various strategies and tactics employed. There was no misreading on my part.
Your post was fine right up to the part where a personal attack was made, violating the TOS and leaving me no choice but to remove it. Frog knew that this would be the case. Nothing personal and I do enjoy your posts, but I have to follow the rules which to be fair are there for a good reason.
Apart from the information W2P published on RB, the other figure I have seen is the following from the paclitaxel patent application:
"DNA1160WO 20 [0038] As disclosed herein, the sequences of at least seven genes are associated with and predictive for variable PC response (see Table 6). Furthermore, when considered within the context of a complex (multifactorial) framework, about 98% of the variability in patient response is explained."
Gold Eagle, thanks for this. It seems that Monica and Richard do work on site and not remotely as some have (often) suggested.
OT Ann, hope you didn't think I was being condescending. I took the opportunity to point out the rather odd system of filing press releases in multiple places on the DNAP website, for the benefit of those not familiar with it.
Ann, almost certainly it is an old one whatever it is. I agree that omitting the year from the dates of the press releases is a nuisance. I often have to go back to the archive on the company website to see when exactly some of them were released.
For reference, the old press releases (June 2000 - June 2003) are on this page:
http://www.dnaprint.com/press.html
The recent press releases (December 2002 onwards) are on this page:
http://www.dnaprint.com/2003/pressreleases/pr.html
It quotes one of the Corixa patents:
"These data suggested that the CORS26 parkinson's gene might play an important role in skeletal development. Related disease, polypeptides have been reported useful for diagnosing and treating alzheimer's lung cancer(WO199938973-A2, FRUDAKIS T N, LODES M J, disease and MOHAMATH R, REED SG; 05-AUG-99; (CORI-) CORIXA..."
ifida, yes lol:
http://www.investorshub.com/boards/read_msg.asp?message_id=3265067
BTW, I couldn't help noticing that WO 2003/048318 (METHODS FOR THE IDENTIFICATION OF GENETIC FEATURES) was updated yesterday - the international search report was included. The PCT database only has the front page update currently though...
On another note it looks as if I might not be able to attend the shareholders meeting after all, a shame as I was looking forward to meeting some of you. There will be another opportunity.
Although the report is largely a reworking of previous material there are one or two really interesting insights. For instance, ABD/DNAWitness 3.0 are currently in trials (together with Ovanone and Statnome). Or what about: "The Company is expecting to complete commercialization of the product [Retinome] with grants from the National Institutes of Justice."
I wondered about this wording when I read the press release yesterday:
"...the new service fulfills a Company need to ensure that the results match the sample."
This might be a chain of custody consideration here - the company having to observe stringent chain of custody requirements as part of gaining accreditation and operating as a normal forensics laboratory. There might be a potential issue with future cases where DNAWitness has been used, and a STR test has not been used at the same time to authenticate the sample and match the two results. Offering the STRmap service now in conjunction with DNAWitness is, in this scenario, paving the way for something they might have to do anyway.
Robert, yes it was mentioned in the Family Tree Legends PR:
http://www.dnaprint.com/2003/pressreleases/pr_05_07_04.htm
In which it was referred to as "STR Map" rather than "STRmap".
How is it different from the standard CODIS STR test? Did you see this bit at the very bottom of the PR:
"The new STRmap test measures the same thirteen genetic locations that are used in the FBI's CODIS national database of felons, and uses an additional two genetic locations making it extremely powerful."
A source such as this one will give details of the two additional STR markers:
http://www.cstl.nist.gov/biotech/strbase/pub_pres/Butler2003a.pdf
"Fifteen autosomal STR markers (the 13 CODIS core loci and D19S433 and D2S1338) were typed..."
These fifteen seem to be used by most people. Like you, I suspect there is more to come (hopefully in the not too distant future).