Dr Yokoyama is the author of Clofibric Acid, a Peroxisome Proliferator-activated Receptor Alpha Ligand, Enhances a Suppressive Effect of Cis-diaminedichloroplatinum on Proliferation of Ovarian Carcinoma Cells which was recently published in Clinical Medicine Insights: Oncology.

Hum Genet. 2010 Mar 6. [Epub ahead of print]

As a result of the several recent genealogy TV shows (Faces of America and Who Do You Think You Are) and a segment on a recent Oprah show, 23andMe is offering a $200 discount on either their Ancestry Edition or their Complete Edition.    This brings these prices down to $199 and $299, respectively.

If anyone is interested in either of these, email me here and I’ll tell you how to do it.

This offer is only good until March 31, 2010.

If you would like to be able to post articles to this blog, please let me know.

Dr. Centeno is offering stem cell therapies for orthopedic damage with remarkable results. Is this the future of stem cells in the US?

The FDA has yet to approve stem cell therapies for general use in medicine, but that hasn’t stopped doctors in Colorado from providing them anyway. Chris Centeno and John Schultz have boldly formed Regenerative Sciences Inc. in Broomfield, Colorado. RSI provides its patients with the Regenexx procedure, an adult stem cell transplant that uses your own cells (autologous) to treat joint injuries and bone damage. There’s no surgery needed. A needle extracts bone marrow, RSI isolates the stem cells and cultures them in your own blood, and then these cells are injected into the area where they are needed. They’ve treated 348+ patients with 800+ injections and show no signs of slowing down. According to RSI’s own surveys, 89% of their knee patients showed marked improvement, as did 75% of their hip patients! Within months some patients can walk or run in ways they haven’t been able to in years. We’ve seen these kinds of results from stem cell treatments before, but only in horses and dogs. That’s because human stem cell therapies like this one aren’t approved by the FDA. How can Centeno and Schultz flaunt the lack of federal approval? They claim that Regenexx is solely used as a part of their medical practice, only within the state of Colorado, and as such is no more regulated by the FDA than it would be by the FAA or the Department of Motor Vehicles. I had a chance to talk with Dr. Centeno over the phone and learn more about Regenexx and RSI. For hundreds of patients, he and his team are providing a remarkable hope. They’ve brought lab-cultured medical stem cell therapies to the US. Finally.

Stem cells have been a focal point for hype and hope for years now. Besides healing horses and dogs, they have promising effects on diabetes, corneal blindness, even HIV. It’s pretty clear that they’re also the future of organ transplants. Just the news of a stem cell related development or patent will cause a biotech company’s stocks to soar. The FDA, which regulates all interstate drug sales and related clinical trials is not trying to keep Americans from these “miraculous” cures, it’s simply trying to make sure they are safe first. Apparently, that’s taking too long. Medical tourism agencies are starting to cater to those seeking stem cell treatments. Whether or not they are ready for widespread medical use, stem cell therapies are in high demand, not just in the US but around the world. It’s no longer a question of when we will have access to these treatments, it’s a question of how.

A severely damaged knee healed to a remarkable degree. Must be stem cells. RSI is offering adult stem cell therapies in the US. That’s an important first, but what will happen without FDA approval?

Patient’s interested in the Regenexx procedure face what seems to be a fairly standard experience for autologous stem cell transplants. It takes 20-40 minutes to extract the cells from hip bone marrow with limited anesthesia, and blood is also taken. Over a month RSI’s lab will isolate mesenchymal (multipotent) adult stem cells and multiply them until they have 1 to 10 million. Typically, a patient will receive an injection into the treated area once a month for three months. Positive results are sometimes seen quickly (in 1 to 3 months) but will hopefully develop within 6 to 9 months. Importantly, there’s no down time as a result of the procedure. Patients can leave the clinic and go home after each injection.  A round of Regenexx (extraction, cultivation,  and 3 injections) costs $7000-$8500. Those who produce exceptional numbers of stem cells can use subsequent injections (even in other parts of the body) for around $3500. Most insurances will not cover the treatment.
The fact that RSI isolates and cultures (multiplies) the cells is a big difference from other clinics that offer stem cell therapies. That process allows the lab to create enough mesenchymal stem cells  to really have an effect on the area in which they are injected. Many clinics around the world will take blood, marrow, or tissue and then spin out the stem cells in a centrifuge, injecting them back in on the same day. That style  of therapy could possibly be effective, but it is far less likely than with a dose of millions of multipotent stem cells. There are several doctors around the US that will provide such ’single-visit’ stem cell therapies, but as far as I know RSI is the only that offers the lab cultured mesenchymal therapy in the US. Dr. Centeno has confirmed that he’s the only one, that he knows of, openly using this particular procedure in the US.
In the past, I have been very skeptical of stem cell treatment centers in other countries. I’d like to turn that same critical eye to Regenexx. It’s only fair. First, let’s look at the success RSI is selling. Autologous transplants are offered in the hands, hips, knees, shoulders, back (non-spinal cord injury), ankles, and bone fractures. For each of these procedures you can find many ardent and exceptionally encouraging patient testimonials on their website, or their YouTube channel, along with a flood of supportive media. Here’s a clip from a local news Channel which is pretty indicative of the rest:

Overall, RSI is claiming around 80% patient satisfaction according to its own surveys. That’s incredible, especially when you see some of their patients walking and running again on joints that have experienced years of chronic damage. It also seems Centeno and Schultz have the documented evidence to back up the claims for Regenexx’s success. RSI provides case studies for each of its treatments as well as published scientific research. According to my conversation with Centeno, RSI is currently working on a comprehensive statistical analysis of their more popular treatments so they can publish quantitative results in a peer review journal. In other words, they’ll soon publish the hard numbers – X% of patients feel Y% better Z months after the procedure.
Importantly, RSI seems to be upfront with patients about the limits of their own technique. The website FAQ clearly states that not all results will be like the testimonials, and they even have adedicated page explaining that stem cell therapies won’t work for everyone. Furthermore, RSI has published the largest study of risks and complications associated with stem cell treatments yet produced in the US (N=227). That paper demonstrates the very low harm associated with stem cell therapies – much lower than the alternative surgery(published in Current Stem Cell Research & Therapy). Centeno told me that if we’re really worried that autologous stem cell therapies are going to hurt someone, this paper pretty much shows they won’t.
The concerns most people have with RSI are not medical, they’re political. Many applaud Centeno and Schultz for supplying the public with the cutting edge technology they demand, but worry about the manner in which it has been accomplished. Skirting FDA approval for a technique through the arguments they use opens the gate to a host of problems. If RSI can provide Regenexx because it is a doctor’s procedure not involved in interstate commerce, does that mean someone else can do the same for another treatment? What are the limits of such procedures? How does a patient know if a doctor’s therapy is safe, or effective, if it hasn’t undergone peer review and government inspection?
During my conversation with Dr. Centeno, he pointed out that doctors and surgeons are developing new procedures all the time. Surgeons will often create new devices for their own use in surgery, doctors routinely try out new dosing regimes, or therapies on their patients. This is part of the medical profession.
Still, it’s possible that even though RSI is doing what many other doctors routinely do (develop a new therapy for use in their own practice) that the federal government could try to bring them to court. The FDA seems to have taken the stance that all stem cells (whether used autologously or not) are drugs. As such, they would need FDA approval, and would likely only be developed by large pharmaceutical companies.
According to Lee Buckler of Cell Therapy Blog, Centeno’s already received a warning letter from the FDA. Centeno clarified that this is actually an “untitled letter” which has no bearing on regulation. He pointed me to this explanation on untitled letters. RSI has faced concerns from the New York Department of Health, and went so far as to pursue a provisional license, even though they are no where near NY state. Clearly RSI is hoping to avoid bureaucratic problems or at least be very prepared for them if they do arise.  Perhaps with enough positive results they can avoid legal battles and even convince insurance companies to cover Regenexx.
Hopefully so. Just look as these results. They’re pretty damn amazing. If you accept the success rates, and the possibilities for long term healing…I know people who need this. I really want them to be able to get it.
Centeno says he is working with others to provide the framework through which many more patients could receive mesenchymal stem cell therapies. He’s on the board of the International Cell Medicine Society (ICMS) which is working to track stem cell therapy patients through a registry, as well as certify stem cell clinics for practice. Through conferences and seminars, doctors are trained in IVF to work in fertility clinics. Centeno explained to me that a similar practice could instruct and track physicians interested in providing lab cultured autologous stem cell therapies. In other words, the technique used by RSI could become a regularly seen procedure in specialty clinics across the country. That may mean more patients could have access to stem cells soon.
One way or another, I know they will. FDA approval is slow, but it’s coming. Athersys has a patent for a stem cell derived drug, other companies have therapies in clinical trials. Those treatments will be here some day. In the meantime, RSI is filling in the gap. Their work may even catch on as a trend. If largely successful, insurance companies may pay for it and the federal government may end up grandfathering Regenexx in at some point. It could happen. What’s certain is that the public demand for stem cell therapies is real, growing, and seemingly justified. When that sort of pressure for a technology exists nobody can keep it down.
**Update: It has been pointed out that we have neglected to consider the long term effects of stem cell therapies. This is an oversight on our part, but the reality is that there is no conclusive understanding of what the long term effects of stem cells treatments will be. We do not know if a stem cell treatment will be effective 5-10 years after it is administered, and we know of no large study that has conclusively reviewed patients for cancer, or any long term side effect 5-10 years after a stem cell injection. I believe that part of what ICMS is trying to do (reviewing clinics, tracking patients results over the long term) may yield a better understanding in the future.**
[image credit: Denver Business Journal, Regenerative Science Inc]
[video credit: ABC 7 News in Denver via Regenexx (copyright status unknown)]
[Sources: Regenerative Sciences Inc, ABC 7 News in Denver, Lee Buckler , RSI Blog, Current Stem Cell Research & Therapy]

Whit Athey is one of those smart guys we all wish we were.    He’s a retired physicist with a doctorate in physics and biochemistry.    He wrote the Y Haplogroup Predictor that many of us use.    He also explains things.

I want to share his response to a recent question about 23andMe ‘matching’ on the ISOGG list.

The question was:

I am missing something in the definition of terms, apparently.    If each parent contributes 50% of his genes to the child, why isn’t the percentage more like 50% than 85%?

On the other hand, if as I think I have read, chimpanzees are 98% the same as humans, why isn’t the comparison of unrelated individuals more in the range of 98%?

If you can, please define the terms being used and explain why a parent and child comparison isn’t 50%.

Whit’s answer:

Yes, all humans are more than 99% identical at each base location.    This is confusing to a lot of people when they get involved with 23andMe data.    The half-million locations or SNPs that were chosen for the Illumina chip (that 23andMe uses) were chosen precisely because they are much more variable than the average location.    People, on average, are alike about 75% of the time at these particular 500,000 locations.    Therefore, being “75% similar on a genome-wide comparison” is just an artifact of the Illumina set of SNPs.    It would be very easy to select 500,000 locations where everyone would be 99% similar (500,000 random locations would probably do the trick), but it would not produce very interesting data.    It would probably be very difficult to find 500,000 locations where people would be only 50% similar  -    maybe impossible  -    I don’t know.

The “genome-wide comparison” is mostly meaningless as I said in my post the other day.    For this particular set of SNPs, you get “genome-wide comparisons” for siblings and parent-child results of around 84% and, of course, about 75% for unrelated people.    If we only had this measure to use, we would get nowhere fast.    It’s the long half-identical segments that are significant.

Maybe you would wonder how even the half-identical segments could be meaningful if there is a 75% probability of being identical anyway at a given location.    While that much is true for a single location, the probability that two consecutive locations would by chance alone have the same base is (0.75)(0.75) = .56 and the probability of 1000 consecutive SNPs having the same base by chance would be (.75)^1000 (to the 1000th power), which is such a small number that I hesitate to try to write it.    Therefore, when 23andMe finds a run of 1000 consecutive SNPs (adjacent on the same chromosome) that have the same state (on one of the chromosomes) they can reliably report that this is significant and could only occur as identical by descent.    The calculation is actually a little more complicated than that because you are comparing two bases for each SNP with two others in another person at each SNP.

Note that the SNP locations occur about every 6000 base locations on average, and the assumption is that if you have, for example, 1000 consecutive matching bases at the locations of the SNPs, then all the bases in between each consecutive pair of SNPs (the other 5999 out of the 6000) are assumed to be the same too, resulting in 6,000,000 consecutive matching bases.    These are the “half-identical segments.”

A parent passes along exactly 50% of his/her 22 autosomal chromosomes to his/her child, so you are right about that.    Depending on how the X and Y are counted in such calculations, you can see how the percentage would be moved slightly off 50%.    The X is much larger than the Y, so your father passes along just as many chromosomes as your mother, but the amount of DNA can be different for sons as for daughters.    I don’t actually know exactly how 23andMe calculates these things, but you can see the potential for some small differences from 50%

I may be beginning to understand . . .

On the left: genetic differentiation between Chinese and Japanese using 420 Ancestry Informative Markers vs. 420 random SNPs. Note that the “fuzzy” picture on B would be better resolved if a larger number of SNPs had been used.

As usual I have my reservations about the time estimates in this paper, but it is very useful as a guide to genetic variation in Indonesia, an island nation of composite origins where the indigenous population forms part of the S/SE Asia/Oceania zone of “Australoids”, probably reflecting early out-of-Africa humans taking the southern route, while this population has been influenced by movements from the north: Caucasoids into India, and Mongoloids or Mongoloid-influenced people into Indonesia.

Journal of Archaeological Science doi:10.1016/j.jas.2010.01.024

Ancestral Puebloan mtDNA in context of the greater southwest

Meradeth H. Snowa et al.

Abstract

Ancient DNA (aDNA) was extracted from the human remains of seventy-three individuals from the Tommy and Mine Canyon sites (dated to PI-II and PIII, respectively), located on the B-Square Ranch in the Middle San Juan region of New Mexico. The mitochondrial DNA (mtDNA) haplogroups of 48 (65.7%) of these samples were identified, and their frequency distributions were compared with those of other prehistoric and modern populations from the Greater Southwest and Mexico. The haplogroup frequency distributions for the two sites were statistically significantly different from each other, with the Mine Canyon site exhibiting an unusually high frequency of haplogroup A for a Southwestern population, indicating the possible influence of migration or other evolutionary forces. However, both sites exhibited a relatively high frequency of haplogroup B, typical of Southwestern populations, suggesting continuity in the Southwest, as has been hypothesized by others ([Carlyle, 2003], [Carlyle et al., 2000], [Kemp, 2006], [Malhi et al., 2003] and [Smith et al., 2000]). The first hypervariable region of twenty-three individuals (31.5%) was also sequenced to confirm haplogroup assignments and compared with other sequences from the region. This comparison further strengthens the argument for population continuity in the Southwest without a detectable influence from Mesoamerica.

Link

A friendly reminder that the new show “Who Do You Think You Are?” will be premiering tomorrow, March 5.    The NBC series features Lisa Kudrow, Sarah Jessica Parker, Spike Lee, Matthew Broderick, Susan Sarandon, Emmitt Smith, and Brooke Shields, and takes each celebrity on a journey back in time as they discover more about the ancestors who came before them.