23andMe already testing for rare Parkinson's mutations?
Posted on: March 23, 2009 9:15 AM, by Daniel MacArthur
This casual aside on a recent post on personal genomics company 23andMe's corporate blog caught my eye:
Mutations in several other genes have also been associated with Parkinson's disease, but these are extremely rare. Many have been found only in one or two families. While these mutations are so rare that they are not covered by 23andMe (to date we have found no customers with any of them), studying them could help scientists better understand the mechanisms of Parkinson's generally... [my emphasis]
In other words, the company already has probes on its custom chip targeting these variants, but it isn't yet reporting results back to customers.
Why isn't it reporting back? If you'd asked me a couple of months ago, I'd say the motivation was probably to avoid the regulatory hassles associated with testing overtly clinical markers - but the company's willingness to provide results for large-effect variants associated with breast cancer pretty much rules that out.
Instead, the most likely reason to hold back on giving results back to consumers is (perfectly reasonable) caution about the reliability of the test. Screening for extremely rare variants is tricky for two reasons: firstly, since there are very few individuals around who carry the mutation, obtaining positive controls is difficult; and secondly, screening accuracy needs to be extremely high to keep down the rate of false positives.
To illustrate that last point, let's say there was a genetic variant with a population frequency of just 0.1% (1 in every 1000 people carry it)*. Now, let's say you have a test with false positive and false negative rates of just 1 in every 1000 tests, and you run that test on one million people. Of the 1000 carriers in the population, the test will only miss one; but it will also give a positive result for 999 people who are non-carriers. In other words, even for this extremely accurate hypothetical test, only 50% of the people who test positive are actually carriers.
This means that testing for rare variants requires exceptionally high standards of accuracy, probably higher than could reasonably be expected from chip-based assays. Given the risks of reporting potentially unreliable results back to customers for serious risk variants it makes good sense for 23andMe to hold off until it has developed extra assays for quality control; and it's unlikely to do this until it has seen at least a few customers who actually do test positive for the variant in question.
As for obtaining samples from real carriers to enable the development of validation assays: what better way to do that than to recruit 10,000 customers suffering from Parkinson's? Targeted recruitment of customers with other diseases will no doubt follow.
It is now abundantly clear that 23andMe is intent on moving into the overtly clinical domain; Navigenics' purchase of its Affymetrix testing lab and deCODE's move into disease-specific genetic tests are other signs that this is a shift that will involve the entire personal genomics industry.
Personal genomics is getting serious.
Monday, March 30, 2009
Saturday, March 21, 2009
Early Parkinson's Treatment With Rasagiline Safe, Well Tolerated, and Effective Versus Placebo
Early Parkinson's Treatment With Rasagiline Safe, Well Tolerated, and Effective Versus Placebo: Presented at ADPD
By Chris Berrie
PRAGUE, Czech Republic -- March 14, 2009 -- Rasagiline monotherapy is safe and well tolerated, with clinical benefits versus placebo in patients with early, previously untreated Parkinson's disease (PD), researchers noted here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).
Early initiation of treatment with rasagiline 1 mg/day also provided significant clinical benefits over later initiation.
A prospective, multicentre study entitled Attenuation of Disease Progression With Azilect Given Once-Daily (ADAGIO) was presented here on March 13 by principal investigator Olivier Rascol, MD, Toulouse University Hospital, Toulouse, France.
"A treatment that slows or halts the progression of disease is a key unmet need in Parkinson's disease," Dr. Rascol stated. He and his colleagues utilised a delayed-start design in their randomised, double-blind, placebo-controlled trial to allow separation of disease-modifying effects from symptomatic effects in the examination of patients with moderate to advanced PD taking rasagiline monotherapy and combination therapy with levodopa.
Patient diagnosis was for cardinal PD signs -- resting tremor, bradykinesia, and rigidity -- with inclusion requiring a disease duration of less than 18 months from diagnosis and investigator judgement of no requirement for additional anti-PD treatment in the following 9 months.
The 1,176 patients enrolled were 61.1% male, with mean baseline characteristics as follows: age, 62.2 years; PD duration, 4.5 months; total Unified PD Rating Scale (UPDRS) score, 20.4; motor-UPDRS score, 14.2; and modified Hoehn and Yahr score, 1.5.
The study followed 2 phases: a 36-week placebo-controlled phase 1, followed by a 36-week full active-treatment phase 2. Randomisation was to 4 groups -- 2 of placebo followed by rasagiline 1 or 2 mg/day for delayed-start treatment (n = 595) and 2 of rasagiline 1 mg/day (n = 288) or 2 mg/day (n = 293) for the full 72 weeks. There were no significant baseline differences across these groups.
With rasagiline 1 mg/day, the 3 specific primary efficacy endpoints were met:
A. The slope in weeks 12-36 of phase 1 was significantly superior with active treatment versus placebo (difference, -0.05; 95% confidence interval [CI], -0.08 to -0.01; P = .0133).
B. Results from the early-start group were significantly superior to those of the late-start group at week 72 (difference, -1.7; 95% CI, -3.15 to -0.21; P = .025).
C. The noninferiority of the slope of early versus late start was met (difference, 0.0; 90% CI, -0.04 to 0.04; P < .0001).
The rasagiline 2-mg/day treatment showed significant benefit in phase 1 versus placebo (P < .001), but did not show superiority versus the delayed start at the end of phase 2.
The secondary endpoint for changes in total UPDRS score from baseline to week 36 for each rasagiline group was met for rasagiline 1 and 2 mg/day, as adjusted effect sizes of -3.0 (95% CI, -3.9 to -2.2; P < .0001) and -3.2 (95% CI, -4.0 to -2.3; P < .0001) respectively.
Rasagiline monotherapy was deemed safe and well tolerated, with few treatment-related adverse events and few discontinuations (placebo, 2.9%; rasagiline 1 mg/day, 3.1%; rasagiline 2 mg/day, 3.8%).
The researchers concluded that this early treatment with rasagiline 1 mg/day is consistent with disease-modifying effects, noting, "ADAGIO also confirms the symptomatic efficacy of rasagiline monotherapy versus placebo in patients with early [Parkinson's] disease."
Funding for this study was provided by Teva Pharmaceutical Industries Ltd. and Teva Neuroscience, Inc.
[Presentation title: The ADAGIO Delayed-Start Study Demonstrates That Early Rasagiline Treatment Slows UPDRS Decline. Abstract P1-423]
By Chris Berrie
PRAGUE, Czech Republic -- March 14, 2009 -- Rasagiline monotherapy is safe and well tolerated, with clinical benefits versus placebo in patients with early, previously untreated Parkinson's disease (PD), researchers noted here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (ADPD).
Early initiation of treatment with rasagiline 1 mg/day also provided significant clinical benefits over later initiation.
A prospective, multicentre study entitled Attenuation of Disease Progression With Azilect Given Once-Daily (ADAGIO) was presented here on March 13 by principal investigator Olivier Rascol, MD, Toulouse University Hospital, Toulouse, France.
"A treatment that slows or halts the progression of disease is a key unmet need in Parkinson's disease," Dr. Rascol stated. He and his colleagues utilised a delayed-start design in their randomised, double-blind, placebo-controlled trial to allow separation of disease-modifying effects from symptomatic effects in the examination of patients with moderate to advanced PD taking rasagiline monotherapy and combination therapy with levodopa.
Patient diagnosis was for cardinal PD signs -- resting tremor, bradykinesia, and rigidity -- with inclusion requiring a disease duration of less than 18 months from diagnosis and investigator judgement of no requirement for additional anti-PD treatment in the following 9 months.
The 1,176 patients enrolled were 61.1% male, with mean baseline characteristics as follows: age, 62.2 years; PD duration, 4.5 months; total Unified PD Rating Scale (UPDRS) score, 20.4; motor-UPDRS score, 14.2; and modified Hoehn and Yahr score, 1.5.
The study followed 2 phases: a 36-week placebo-controlled phase 1, followed by a 36-week full active-treatment phase 2. Randomisation was to 4 groups -- 2 of placebo followed by rasagiline 1 or 2 mg/day for delayed-start treatment (n = 595) and 2 of rasagiline 1 mg/day (n = 288) or 2 mg/day (n = 293) for the full 72 weeks. There were no significant baseline differences across these groups.
With rasagiline 1 mg/day, the 3 specific primary efficacy endpoints were met:
A. The slope in weeks 12-36 of phase 1 was significantly superior with active treatment versus placebo (difference, -0.05; 95% confidence interval [CI], -0.08 to -0.01; P = .0133).
B. Results from the early-start group were significantly superior to those of the late-start group at week 72 (difference, -1.7; 95% CI, -3.15 to -0.21; P = .025).
C. The noninferiority of the slope of early versus late start was met (difference, 0.0; 90% CI, -0.04 to 0.04; P < .0001).
The rasagiline 2-mg/day treatment showed significant benefit in phase 1 versus placebo (P < .001), but did not show superiority versus the delayed start at the end of phase 2.
The secondary endpoint for changes in total UPDRS score from baseline to week 36 for each rasagiline group was met for rasagiline 1 and 2 mg/day, as adjusted effect sizes of -3.0 (95% CI, -3.9 to -2.2; P < .0001) and -3.2 (95% CI, -4.0 to -2.3; P < .0001) respectively.
Rasagiline monotherapy was deemed safe and well tolerated, with few treatment-related adverse events and few discontinuations (placebo, 2.9%; rasagiline 1 mg/day, 3.1%; rasagiline 2 mg/day, 3.8%).
The researchers concluded that this early treatment with rasagiline 1 mg/day is consistent with disease-modifying effects, noting, "ADAGIO also confirms the symptomatic efficacy of rasagiline monotherapy versus placebo in patients with early [Parkinson's] disease."
Funding for this study was provided by Teva Pharmaceutical Industries Ltd. and Teva Neuroscience, Inc.
[Presentation title: The ADAGIO Delayed-Start Study Demonstrates That Early Rasagiline Treatment Slows UPDRS Decline. Abstract P1-423]
Saturday, March 14, 2009
Long Term Results Similar in Two Parkinson's Medications
By Will Dunham
WASHINGTON, March 9 (Reuters) - People with Parkinson's disease may worry over which of two kinds of medications to use when first starting treatment, but a study published on Monday indicates the results are similar either way.
Researchers compared disability levels and quality of life after six years for people who started out taking either the standard generic drug levodopa or privately held German drug maker Boehringer Ingelheim's Mirapex, also called pramipexole.
The two drugs are generally employed as the first line of treatment for Parkinson's disease. In different ways, they address the decline in production of the brain chemical dopamine that occurs with the disease.
Parkinson's undermines control over movements and speech. Patients can have stiffness or rigidity of the arms and legs, slowness or lack of movement, and walking difficulties, along with tremors in their hands, arms, legs, jaw or face.
Levodopa is seen as better to deal with mobility issues and tremors. But it can cause involuntary movements known as dyskinesia, and its effectiveness also may wear off over time.
Mirapex may be less effective at handling motor control symptoms and can cause sleepiness. But it is less likely to cause involuntary movements or lose effectiveness over time.
"Despite a little bit of variations in how people were doing in specific areas, in terms of overall quality of life and disability measurements, the two groups looked the same," University of Rochester Medical Center neurologist Dr. Kevin Biglan, one of the researchers, said in a telephone interview.
"Then it becomes more of an individual decision in terms of short-term issues and individual preferences about some of these complications, potentially," he said.
Mirapex is in a class of drugs called dopamine agonists that also includes GlaxoSmithKline's (GSK.L) (GSK.N) Requip, or ropinirole.
The researchers tracked 222 patients in the study published in the journal Archives of Neurology.
Of those who started on Mirapex, 90 percent of them ended up also taking levodopa, a drug that has been around for more than four decades, Biglan said. But the side effects differed depending on which drug they started on, he added.
"There's been all this research trying to address what's the better initial treatment strategy. And patients have struggled with whether they were making the right decision in terms of what treatment to go with initially," Biglan said.
"So they could probably make a decision regarding either treatment without being overly worried about the long-term implications," he added. Boehringer funded the study. (Editing by Julie Steenhuysen)
WASHINGTON, March 9 (Reuters) - People with Parkinson's disease may worry over which of two kinds of medications to use when first starting treatment, but a study published on Monday indicates the results are similar either way.
Researchers compared disability levels and quality of life after six years for people who started out taking either the standard generic drug levodopa or privately held German drug maker Boehringer Ingelheim's Mirapex, also called pramipexole.
The two drugs are generally employed as the first line of treatment for Parkinson's disease. In different ways, they address the decline in production of the brain chemical dopamine that occurs with the disease.
Parkinson's undermines control over movements and speech. Patients can have stiffness or rigidity of the arms and legs, slowness or lack of movement, and walking difficulties, along with tremors in their hands, arms, legs, jaw or face.
Levodopa is seen as better to deal with mobility issues and tremors. But it can cause involuntary movements known as dyskinesia, and its effectiveness also may wear off over time.
Mirapex may be less effective at handling motor control symptoms and can cause sleepiness. But it is less likely to cause involuntary movements or lose effectiveness over time.
"Despite a little bit of variations in how people were doing in specific areas, in terms of overall quality of life and disability measurements, the two groups looked the same," University of Rochester Medical Center neurologist Dr. Kevin Biglan, one of the researchers, said in a telephone interview.
"Then it becomes more of an individual decision in terms of short-term issues and individual preferences about some of these complications, potentially," he said.
Mirapex is in a class of drugs called dopamine agonists that also includes GlaxoSmithKline's (GSK.L) (GSK.N) Requip, or ropinirole.
The researchers tracked 222 patients in the study published in the journal Archives of Neurology.
Of those who started on Mirapex, 90 percent of them ended up also taking levodopa, a drug that has been around for more than four decades, Biglan said. But the side effects differed depending on which drug they started on, he added.
"There's been all this research trying to address what's the better initial treatment strategy. And patients have struggled with whether they were making the right decision in terms of what treatment to go with initially," Biglan said.
"So they could probably make a decision regarding either treatment without being overly worried about the long-term implications," he added. Boehringer funded the study. (Editing by Julie Steenhuysen)
Saturday, March 7, 2009
NIH awards $4 million to Iowa State veterinary researchers for Parkinson's disease research
NIH awards $4 million to Iowa State veterinary researchers for Parkinson's disease research
Mar 5, 2009
DVM NEWSMAGAZINE
Ames, Iowa- An NIH-affiliated organization recently doled out more than $4 million in grants to two veterinary researchers at Iowa State University (ISU) to further study Parkinson's disease.
The researchers at the Iowa Center for Advanced Neurotoxicology (ICAN) at ISU received the financial support from the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH).
The awards represent innovative approaches to funding biomedical research in Parkinson's disease by NINDS, the university reports in a prepared statement.
Dr. Anumantha Kanthasamy, a faculty member in the Department of Biomedical Sciences at ISU's College of Veterinary Medicine and director of ICAN, secured the funding for a new NIH Multi-Principal Investigators Award program. This award is intended to foster interdisciplinary biomedical research among multiple institutions, the university explains.
Kanthasamy will collaborate with Dr. Balaraman Kalayanaraman, chair and professor of the Department of Biophysics at the Medical College of Wisconsin, in developing a novel class of antioxidant-based therapeutic agents for the treatment of Parkinson's Disease. A total of $2.77 million in NIH funding will be provided to their project. ISU will receive about $1.4 million from the award over the next five years.
Dr. Arthi Kanthasamy, another ICAN researcher in neurotoxicology and a faculty member in the Department of Biomedical Sciences at ISU, received an award from the NINDS' New Investigator Award program. She will receive a total of $1.28 million for her work in studying the brain inflammatory mechanisms in Parkinson's Disease models. Arthi Kanthasamy currently researches degenerative processes in stroke models and also teaches pharmacology and histology courses to graduate and veterinary students.
"To receive, not only one, but two awards for work in Parkinson's disease reflects positively on the quality of research being conducted at ISU," says Dr. John Thomson, dean of ISU's College of Veterinary Medicine.
ICAN was created to promote interdisciplinary research related to neurotoxicological problems in both animals and humans. Neurotoxicology bridges the scientific fields of toxicology and neuroscience and plays a key role in the health of humans and animals, the veterinary college reports.
Mar 5, 2009
DVM NEWSMAGAZINE
Ames, Iowa- An NIH-affiliated organization recently doled out more than $4 million in grants to two veterinary researchers at Iowa State University (ISU) to further study Parkinson's disease.
The researchers at the Iowa Center for Advanced Neurotoxicology (ICAN) at ISU received the financial support from the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH).
The awards represent innovative approaches to funding biomedical research in Parkinson's disease by NINDS, the university reports in a prepared statement.
Dr. Anumantha Kanthasamy, a faculty member in the Department of Biomedical Sciences at ISU's College of Veterinary Medicine and director of ICAN, secured the funding for a new NIH Multi-Principal Investigators Award program. This award is intended to foster interdisciplinary biomedical research among multiple institutions, the university explains.
Kanthasamy will collaborate with Dr. Balaraman Kalayanaraman, chair and professor of the Department of Biophysics at the Medical College of Wisconsin, in developing a novel class of antioxidant-based therapeutic agents for the treatment of Parkinson's Disease. A total of $2.77 million in NIH funding will be provided to their project. ISU will receive about $1.4 million from the award over the next five years.
Dr. Arthi Kanthasamy, another ICAN researcher in neurotoxicology and a faculty member in the Department of Biomedical Sciences at ISU, received an award from the NINDS' New Investigator Award program. She will receive a total of $1.28 million for her work in studying the brain inflammatory mechanisms in Parkinson's Disease models. Arthi Kanthasamy currently researches degenerative processes in stroke models and also teaches pharmacology and histology courses to graduate and veterinary students.
"To receive, not only one, but two awards for work in Parkinson's disease reflects positively on the quality of research being conducted at ISU," says Dr. John Thomson, dean of ISU's College of Veterinary Medicine.
ICAN was created to promote interdisciplinary research related to neurotoxicological problems in both animals and humans. Neurotoxicology bridges the scientific fields of toxicology and neuroscience and plays a key role in the health of humans and animals, the veterinary college reports.
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