Understanding Genetic Testing & Sequencing – It’s Greek To Me

We have recently learned from the Mayo Clinic that our twins Addi and Cassi have one Niemann Pick Type C gene mutation that has been identified in their bodies — it’s called Exon 12 DNA Change 1920delG.   This DNA sequence change (or deletion) is a “known pathogenic mutation in the sterol-sensing domain.”   The 1920delG mutation leads to a premature stop in the synthesis of the protein after 655 residues, instead of the normal 1278 residues.  We were told that because of the position of Addi and Cassi’s mutation, the lab at Mayo could only get clean DNA sequencing in the forward direction.  We are still trying to figure out what all of this means.

The second mutation in the twins have so far has proved elusive to Mayo Clinic researchers.  At this point, Hugh and I need to have our Niemann Pick Type C genes on Chromosome 18 sequenced in order to try identify our family’s second mutation.  Next week, we will have our blood drawn and sent to Mayo for analysis and hope to find the second mutation.  By finding our genetic mutations, we can learn clues about Niemann Pick Type C disease.  We have also found out that Addi and Cassi do not have a common NPC mutation — that mutation is called I1061C.  It gets more complicated for us and the mystery deepens.

I wonder if I have the Exon 12 DNA Change 1920delG in my body?  Or is Hugh the carrier of this faulty gene?   Which one of us has the gene that is proving elusive and hiding?   How did this even happen to us and our family?  This mystery goes back thousands of years and is so bizarre and so complicated that I simply don’t want to think about it anymore tonight.   God only knows what will happen in my dreams.  Each night, I am afraid to close my eyes for fear as to how my unconscious mind will take over  — my nightmares are beyond comprehension.

Life Versus Freezers

If you were a frozen embryo, would you rather die in a freezer or donate your life to science? It seems like a very easy choice to make, don’t you think? I have never had to think much about the stem cell debate before Addi and Cassi were diagnosed with a rare and fatal disease but now stem cell research is at the forefront of my mind.Stem cell research could someday save  children who are suffering from Niemann Pick Type C and other deadly childhood diseases.

I ask any person who is opposed to stem cell research to put themselves in our position — our children are on a path to losing their minds and will suffer a most horrific death if we don’t accelerate scientific research across the board, including into stem cells.

I tend to fall into the more conservative camp on a number of moral and political issues but I have been thinking about my vote in the upcoming 2008 election. I want to support candidates who will work to allow science to move forward while addressing the main moral conundrum.  Because we are faced with this horrible situation, I am quickly understanding that the Bush administration’s position on this subject is simplistic and naive.

All I can think about is Addi and Cassi ending up dead in a freezer …just like these embryos. Why? If embryos are "life" it seems to me that these embryonic "children" would be honored to give up their lives to save other children like Addi and Cassi who in turn might end up giving their lives to try and solve one of the most complex brain mysteries in science. Children should not be in freezers – left to die as an embryo or dead from a disease that can be solved. It’s time to let scientists and researchers do their jobs — to save lives, including yours, your children and your grandchildren.

The following is a quote from a letter to the editor of the Reno Gazette Journal in January 2007 written by Lawrence Goldstein, a Howard Hughes Medical Institute Professor and Department Of Cellular and Molecular Medicine Director for UC San Diego Stem Cell Program.

"It’s unfortunate that those opposed to embryonic stem cell research have jumped to the wrong conclusion once again about the recent report that a new cellular reprogramming method might eliminate the need for embryonic stem cells. There are two important facts about this exciting recent advance in reprogramming adult cells: first, this advance was possible only because of work done with embryonic stem cells; second, like most stem cell advances, we are still early in our understanding of the implications of these findings.

What remains certain is that thousands of embryos will die in the coming years in freezers across this country and around the world. There is abundant genetic diversity in those frozen embryos that could be a lifesaving source of novel therapies for devastating diseases. Scientists have never argued that embryonic stem cells have the only medical potential. Scientists do say that policymakers should not tie the hands of science by allowing us to look through only one door in our quest for new disease treatments."  Read the entire letter here.

Clearly, this issue is extremely complicated. I do not support the creation of embryos purely for scientific purposes. However, the harsh reality is that 10s if not 100s of thousands of embryos are currently being stored in freezers for "family building."  Of those, many will never turn into children like Addi and Cassi and thus will be destroyed by fertility clinics. As a society, we have already accepted the creation of embryos outside the body for the purpose of creating life and in vitro created children are filling up classrooms everywhere. The possibilities of embryonic stem cell research are limitless. These embryos, who are now living under a death sentence in freezers, should be entitled to a right to life by living on in others through helping solve complex medical problems.

Finally, let’s hope we can create stem cells from other reprogrammed cells so the embryo debate can be over (Newsweek’s most recent article).

A Law Against Lawyers!

I am posting this message to the entire world to let everyone know that Hugh and I will not sue any doctor, scientist, researcher, hospital or non-profit if anything happens to Addi and Cassi as we embark on trying experimental treatments to save them from Niemann Pick Type C disease.  No matter what happens during this journey, we assure you we will not take legal action against you and we are putting this is writing for the world to see.  We are also willing to sign any release form necessary.  Of course, this release form would need to be drawn up by lawyers!

Oh, the lawyers!  There really needs to be a law against lawyers. The entire medical system is paralyzed because everyone in the ecosystem is living in fear of litigation.  I can tell you that the medical system as it is working today is keeping children like ours from getting the types of treatments they desperately need.  It has come to the point where doctors can’t even dispense an aspirin or an antibiotic out of fear of malpractice.  There are too many bureaucrats who in turn are afraid of the lawyers and who literally want to stand in our way of getting productive treatments accomplished.  I have come to understand that there are people in the medical and research system who do not want to help us, they simply want to keep their jobs and not get sued or are interested in publishing their next scientific paper.

Then there is someone like Mike Alonso at Jones Vargas, a lawyer who has been particularly helpful in making connections for us during this most difficult time.  Talk about world-class.

And of course there is Dr. Marc Patterson, Addi and Cassi’s pediatric neurologist from the Mayo Clinic.  Every single doctor in America should take a lesson from Marc Patterson on how to care for patients and what it means to be a doctor.  Someone who you would expect would have a huge ego since he is one of the brightest people on the planet does not have one.   I have not met one person who has not said, “Marc Patterson and wonderful” in the same sentence.

Dr. Steve Walkley at Einstein University and Dr. Dan Ory at Washington University who are true collaborative research scientists, who believe in openness, data accessibility and science for the people.  These are a few of the people who keep me hopeful that even despite the lawyers and the bureaucrats and the sickness that exists throughout our medical system, there can be a new paradigm for how rare diseases like Niemann Pick Type C are treated and cured in the future.

Santa Really Is Coming To Town!

A telephone call from an unknown number came to our house on Friday night.  It was Mrs. Claus on the line calling to inform us that Santa would be arriving at our house from the North Pole between 5:30pm and 6:00pm on Christmas Eve to bring Addi and Cassi their Christmas presents.  This is the time Santa arrives in Reno and apparently he’s very busy so we better be prepared to take video.  Mrs. Claus also reminded us that when Santa leaves the house the girls need to go to the backyard to look for the Rudolph and the rest of the reindeer so they don’t see Kris Kringle getting into his pickup truck!

The kindness people have show us over the past few months is extraordinary to say the least. Yesterday, a friend of mine stopped by with a set of darling CureCaps made by a friend of hers who lives here in Reno.  Carol, our friend in Boston, spent two solid weeks knitting CureCaps day and night and is helping us get the word out about Addi and Cassi on the East Coast.

Our friends from Australia offered to donate their beach house and a round of golf at the Royal Melbourne Golf Club, one of the top golf courses in the world, for our fundraiser and silent auction in May 2008.   We have received pedicure donations, housecleaning service, the condo on Lake Tahoe…the donations go on and on.  Many people are offering their personal time to help us as well.  The outpouring of support on so many different levels is incredibly moving and keeps us focused on our goal to conquer cholesterol and beat NPC.

A number of checks have also come to the house to the Addi and Cassi Fund.  The donations come in large and small amounts — $10,000, $1,000, $500 and even $10.  Many of the checks are coming from people we have never met and they arrive with touching letters of support and encouragement. To everyone this Christmas, we wish you much love, peace and joy.

The Hempel Family

“I” for Insane, “R” for Ridiculous, “B” for Broken – America’s Institutional Review Boards

Regulations, Regulations, and more Regulations!

Some people have asked me why I am not blogging about different topics every day. I really wish I could be blogging more but besides having 1000 things on my to do list, I am actually scared to death to actually talk about some things that are happening to us right now out of fear we might not get the help and cooperation we need to try and save Addi and Cassi’s lives. There are many doctors, researchers and scientists who are being highly cooperative and it has been a truly remarkable experience. Thank you!

On the other hand, there are others who are not as cooperative. I have found that there are a lot of major egos in the medical and science community. A lot of science is about publishing papers about experiments in mice and petri dishes, not about finding near term treatments and therapies that can save the lives is kids like Addi and Cassi. The system is certainly not designed around sharing and collaboration – it’s really a collection of silos all competing against each other for funding or who will get the next Nobel Prize. Someday I will have the opportunity to explain more.

What I can and will talk about is IRBs – in my mind the term stands for "Insane, Ridiculous and Broken" ethics oversight committees. I had never even heard of the term “IRB” until a few months ago when a doctor said we have to, “get this idea through the IRB and this is going to take lots of time.”  An institutional review board (IRB), also known as an independent ethics committee (IEC) or ethical review board (ERB) is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the research subjects if they are involved in research studies.

One of the biggest problems we are facing at the moment with Addi and Cassi centers around the IRBs. These IRBs now standing in the way of Addi and Cassi getting critical tests done which will ultimately lead us to therapies more quickly. The bottom line is that IRBs are severely impeding progress of medical research in the United States today and something needs to be done about it at a national level.  I know my rights and I want testing done.

Let me give you an example of just how ineffective an IRB can be when you are facing a rare and fatal disease like NPC and you’re in a sprint, not a marathon, to save your kids lives. The National Institutes of Health (NIH) needs spinal, blood and urine samples from healthy children to compare against NPC children who they are currently studying. Both Addi and Cassi are in the study. If the NIH can compare normal kids samples directly against NPC kids samples, they might actually find something called a biomarker (a sign of illness in the bodies of NPC kids). Piece of cake to get samples, right? Wrong. The problem is it can take MONTHS to put together a “protocol” and get it approved through an IRB. Once you get a “protocol” designed, you need to get group of committed physicians (most likely ER doctors) who will be at the front lines to get consent from families to obtain these specimens.

I have been working with the NIH and my local hospital, Renown Regional Medical Center, to try and make this happen.They both have been very cooperative and are trying to move as quickly as possible under the rules but I’m now seven weeks into this process between getting the protocol, the consent form, and begging our local doctors to participate. I still have to get approval from the local IRB so cross your fingers. Why am I even having to do this? If I don’t do this, it will take months, if not years, to get these samples because there are not enough resources in the NPC community to accelerate the process more quickly.

I told this story to a friend who offered to send her child down to get the blood and urine sample done so we could send them to the NIH immediately. Problem is, you can’t do this, it’s against the "rules."  So while millions of samples are being flushed down the toilet or disposed of on a daily basis at hospitals around the country, kids are dying. These samples literally could provide clues into Niemann Pick Type C that could lead to treatments more quickly. 

This is an absolute nightmare of all nightmares. No parent should be faced with getting a diagonosis of Niemann Pick Type C and then enter into a totally dysfunctional medical and drug development system on top of it. While I realize that IRBs do serve a purpose, the regulations have simply gone too far and therefore are becoming ineffective. It seems like IRBs are far more worried about litigation when they should be focused on saving lives.

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