Navigenics? Who was that?

So after the New England Journal of Medicine has given Personal Genome Sequencing the thumbs down, I ask you...."What will happen to these personal genome companies?"

I have several ideas....

1. They all morph into non-health related information tools. Every bell and whistle that can be marketed that will not face the scrutiny of physicians will come out of the wood works.

2. They will begin to say "The medical field has no sense of what the promise of genomic medicine is" They will attack physicians' lack of genomic knowledge. This is the tactic which nutraceutical companies use. The 'Ol "We have a secret....most physicians don't know or won't share......because they want you to have disease"

3. They will disappear, like the dinosaurs. A neat phenomenon that gave us something to write about for 4 months. Somehow I don't think Google will let that happen. But hey, ya never know.

4. They all will say "Not to be Used to Diagnose or Treat Disease" EVEN NAVIGENICS!!!

5. A new tool that uses evidence based SNP testing to identify risk will come out of the woodwork and crush them all.

6. They will create dating services around their genome scans. "Find out your perfect mate" "Discover the person who you will have super children with"

7. They will contract the Sherpa, buy Helix Health of Connecticut and it's model. Enabling the spread of directed genetic testing and personalized medicine.

8. DNA Direct and direct to consumer targeted testing will begin to partner with traditional models of genetic and genomic healthcare. They will create a more useful alternative to Genome Scanning, leaving Kleiner & Perkins smoldering for not consulting us first.

9. They will keep on, keeping on. Hoping that the limited scans which they now offer will appeal to those persons who bought a space flight, those who bought the cereal box sized mobile phone, or even those who bought Betamax

The Sherpa Says:

We must remember that Genomic and Genetic Health has nothing to do with these companies and everything to do with Personalized Medicine. My concern is that physicians will now be given a free ticket to blow of genetics and genomic healthcare. It is easy for the ignorant to not know what they are missing.

As the NEJM article says "For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets." Detailed patient reports are in the skill sets of my physicians.

2008 Here We Come!!!

After some time off thinking about where Personalized Medicine has been headed and where it could go I have come up with some simple conclusions. But first I want refer all of you to my interview with Bertalan Mesko over at ScienceRoll. Bertalan will be headed over to the US and working with me to educate physicians on Medicine 2.0

Why do I refer you to the interview? Because I breakdown molecularly personalized medical services into several categories. There is much confusion as to the term Personalized Medicine. In fact, Helix Health of Connecticut's marketing team has told us based upon their research that some even mistake this field for concierge medicine!!

This article recently released in the New England Journal of Medicine speaks for what I called Personalized Genetics. For those of you who don't know, in 2006 the nobel prize in medicine and physiology was awarded for the discovery of RNA regulation of protein synthesis. This study is a neat expression of this unique technology. By identifying patients with a "Genetic Disorder" (What disease isn't genetic?) researchers have created a new piece of nucleic acid that will actually tell the machinery in the cell to do something other than it was coded to do.

Say Wha? Ok. Muscular Dystrophy is caused by absence of a certain protein called Dystrophin. If muscle cells can't make this protein, then they cannot function. Children often are wheelchair bound before 10. Why can't they make the protein? Usually, the gene which codes for the protein is defective. Its defect causes the gene to protein machinery to stop making the protein very early in its production. This results in a non-functioning protein. This new product PRO051 tells the machinery to pay no attention to the defect. Instead the machinery keeps going and creates a semi-functional protein.

So why is this Personalized? Well, not all people with Duchenne's have the defect required for this medicine to work. But unlike with Lipitor where the therapeutic success rate is anywhere between 40-50%, PRO051 will be effective in approximately 70% of people. Why? 70% of persons with Muscular Dystrophy have the needed mutation. In people with high cholesterol there are multiple different genetic changes as well as environment. But imagine when we can say "You have high cholesterol because of these genes and this environmental exposure. We will cut out this exposure and tweak these genes just a little bit." Voila, No more Lipitor!

Personalized Genetics could become Personalized Medicine...but not yet. I think this author from the NEJM has read my interview too..

"Personalized molecular medicine." As with other catchy terms for big ideas, such as "reversing global warming" and "renewable energy," the concept of personalized molecular medicine is certainly important, but the path to achieving it is far from clear. When such phrases are considered, definitions are important.

Does personalized molecular medicine mean the tailoring of drugs for the individual patient, an approach that evokes images of Bones on Star Trek making instantaneous diagnoses with his Tricorder followed by loud pneumatic injections of customized drugs? Such a concept would place the realization of this technology in the same time frame as the achievement of "warp drive" that hurtled the Enterprise into new galaxies.
On the contrary, personalized molecular medicine appears to be at our doorstep.

Unfortunately, I don't think Dr. Hoffman is aware of Helix Health of Connecticut. Personalized Medicine is at your doorstep too.....

The Sherpa Says: The conclusions are coming. I think Yoda said it best "Patience" This year will require tremendous amounts of it. Francis Collins tells a joke "There is this woman who is married to a research geneticist. He keeps telling her how great their sex life WILL be." Thank you to a certain unnamed TV news series for thinking of me when covering Personal Genomics. I look forward to our discussions. Does anyone think the New Year's Ball looks like an AAV?

MS genes and GWAS.

Today I want to once again cool the hype from the media. There recently was a study in the New England Journal of Medicine as well as a candidate gene study in the journal Nature Genetics which identify new risk factors for Multiple Sclerosis.

First what we know
Candidate-gene studies have validated associations between multiple sclerosis and polymorphic variants within the major histocompatibility complex (MHC), but no other loci with a definitive association with the disease have been found.

30 years ago scientists found that immune system proteins called HLAs (human leukocyte antigens) are partly responsible for the genetic factor. HLAs are like identity tags, all cells of the body carry them and the immune system "inspects" them so it knows not to attack them when it's seeking out foreign cells or pathogens to destroy. The gene that codes for them is called HLA-DRB1 and having this variant increases one's chance of getting MS by four times.

Second let's take a hard look at the data

From the NEJM Article

A number of allelic variants had a significant association with multiple sclerosis. Of these, two SNPs in intron 1 of the IL2RA gene encoding the alpha chain of the interleukin-2 receptor (also called CD25, located at chromosome 10p15) are notable: rs12722489 (P=2.96x10–8; odds ratio, 1.25; 95% confidence interval [CI], 1.16 to 1.36) and rs2104286 (P=2.16x10–7; odds ratio, 1.19; 95% CI, 1.11 to 1.26)

A nonsynonymous coding SNP (rs6897932) in exon 6 of IL7RA, a gene located on chromosome 5p13 that encodes a transmembrane domain of the IL7R chain of the interleukin-7 receptor (CD127), also showed highly significant evidence of association with multiple sclerosis (P=2.94x10–7; odds ratio, 1.18; 95% CI, 1.11 to 1.26)

The HLA-DR locus was unequivocally associated with multiple sclerosis (P=8.94x10–81; odds ratio, 1.99; 95% CI, 1.84 to 2.15)

Analysis of the 925 SNPs from the MHC region (positions between 29 and 34 Mb on chromosome 6) conditional on HLA-DRB1*1501 revealed a highly significant residual association signal peaking at rs9270986 (P=1.83x10–17; odds ratio, 5.80; 95% CI, 3.53 to 9.53), which lies close to DRB1. A portion of this residual signal is probably related to allelic heterogeneity at DRB1

The study in Nature found similar findings. Before I say shame on the media for hyping this association I would like to put these numbers called odds ratios into context.

An odds ratio of 1 indicates that the condition or event under study is equally likely in both groups. An odds ratio greater than 1 indicates that the condition or event is more likely in the first group. And an odds ratio less than 1 indicates that the condition or event is less likely in the first group. In this case the odds ratio of having MS would be more likely if you carried the studied polymorphisms mentioned above. But not by much!!!

Let me give you an example. In patients who carry a single change in one of their clotting factors, Factor V Leiden the relative risk of developing a blood clot is 7. Yet when combined with other rsik factors like smoking and obesity, only a whopping 10% ever develop blood clots!

Granted relative risk is slightly different than Odds Ratios. It does tend to measure on the more conservative side... since relative risk is a more intuitive measure of effectiveness, the distinction is important especially in cases of medium to high probabilities. If action A carries a risk of 99.9% and action B a risk of 99.0% then the relative risk is just over 1, while the odds associated with action A are almost 10 times higher than the odds with B.
In medical research, the odds ratio is favored for case-control studies and retrospective studies. Relative risk is used in randomized controlled trials and cohort studies. For more explanation click here

I hope you are still following me. What this means is that an Odds Ratio less than 2 is not impressive. In fact it gives misleading data.

The Sherpa Says: Even with the most tightly linked data discovered over 30 years ago, we still have no curative therapies for Multiple Sclerosis. What that means to me is that we have no clue as to the true molecular mechanisms of this heterogeneous disease. Stay away from the DTC tests that will likely spring up from these studies. Never take a test for risk without the Odds Ratio being at least 2. Now shame on you media, for just publishing press releases and not doing the due diligence regarding these findings!

This Week in New England Journal of Medicine

This week in NEJM Armanios et al post a study on telomere repair and Idiopathic Pulmonary Fibrosis. They found that <10% class="blsp-spelling-error" id="SPELLING_ERROR_7">telomere repair genes hTERT/hTR. This condition, as the name idiopathic (or as I like to call it IDIOT-Pathic) states has no known etiology, and no effective treatment. Even worse, by the time you are symptomatic it is nearly too late, as median survival is 3-5 years after diagnosis.

In January the specter of short telomeres was brought up implicated in heart attack. Perhaps telomere testing is the new marker. These studies require replication, but I am convinced that the system of telomere repair is involved in both disease processes.
Stay Tuned.