Nobel Prize Winning Cholesterol Researchers Brown and Goldstein Enter Cyclodextrin Field Of Study

I wonder how many smart cholesterol researchers have Google Alerts set up on Brown and Goldstein Labs?  If they do they might want to read this post about the Nobel Prize winning labs release of a very important cholesterol paper involving cyclodextrin and its modulation of cellular cholesterol metabolism.

With their amazing new research work, Brown and Goldstein have shown that cyclodextrin (hydroxy propel beta cyclodextrin or HPBCD) reverses the block in cholesterol movement out of the lysosome in cultured cells of both the mouse and human Niemann Pick Type C fibroblasts.  The papers are here:

Brown and Goldstein Paper – Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport in Niemann-Pick type C cells

Brown and Goldstein Supplemental Information on Niemann Pick Type C, Cholesterol and Cyclodextrin

For those of you who have no idea what I am talking about, this is very big news in the world of cholesterol research. It’s not every day that Nobel Prize winning cholesterol scientists publish papers on a non toxic sugar compound that is the main ingredient in Febreze air freshener and  fat free food products like butter.

How on earth can cyclodextrin be entering the cell and the lysosome and reversing the Niemann Pick Type C cholesterol genetic defect that is trying to kill our twin daughters?

In this paper, Brown and Goldstein say that the mode of action of cyclodextrin is still unknown. This is remarkable to me because the most famous cholesterol researchers on the planet have been unable to figure out this scientific puzzle. When this is all sorted out, I think a whole new wave of drugs will be developed with this compound that everyone has thought is benign!  I hope it happens fast because this compound could save my girls’ lives.

In conjunction with this news from Brown and Goldstein, Addi and Cassi’s lysosomes are shrinking in size since receiving their cyclodextrin IV infusions.  Measurements of Addi and Cassi’s lysosomes were done with a special assay developed at Oxford University. But is cyclodextrin really crossing the cell membrane and going into the cells in living people?   The previous research on cyclodextrin would say it acts outside the cell membrane.

Addi and Cassi are now six months into their cyclodextrin infusions which were approved by the FDA under “compassionate use” IND applications.  Addi and Cassi are doing quite well with no apparent side effects (except positive effects like better balance and coordination and increased concentration and awareness). But how can this be happening if cyclodextrin does not get through the blood brain barrier?

The data in the twins’ lysosomes  indicates what Brown and Goldstein has found in mice and in cell culture/ fibroblasts could be happening inside Addi and Cassi’s systems as well.  Our next step will be to apply for Orphan Drug Status with the FDA for Cyclodextrin after Thanksgiving.  I am also working with doctors on ways to get cyclodextrin across the blood brain barrier.  I am currently pursing a path to get Cyclodextrin into the CSF of Addi and Cassi.  I think if we can do this we have a better chance to save them from this horrible cholesterol disease that is destroying their brains and causing dementia.

We are going to apply for a FDA grant in February 2010. Cyclodextrin kills the HIV-AIDS virus too.  If we can get the goverment to keep and open mind and get more researchers studying this compound, the possibilities are endless.

ResearchMatch.org Is Cool -The Idea, the Website and even the Logo! Is This Really From The NIH?

Great news from the NIH today — a new service called ResearchMatch.org was announced.  ResearchMatch.org is a national research study recruitment registry announced to help match volunteers with researchers who want them to participate in research studies.

The registries matching model compliments Clinicaltrials.gov (a website that needs a serious facelift!) but  has one fundamental difference. ResearchMatch.org places the burden of connecting the right volunteers with the right study on the researchers, whereas Clinicaltrials.gov asks volunteers to identify the trials that could work for them.

I am going to have my entire family sign up to be part of ResearchMatch.  Imagine if everyone did the same. Researchers could easily find people to participate in studies which in turn would speed up finding treatments and cures for diseases.  One of the biggest problems in research studies today is that a certain number of people are needed to participate in order to find answers but often times there are too few volunteers.  This is a problem we face in Niemann Pick Type C disease — with only 500 children in the world with the disease we have limited volunteers and a small cohort for clinical studies.

Many things created by our government tend to be overly complicated or fall short of their promise. However, ResearchMatch is a smart idea and the website is user friendly and easy to navigate.  In fact, the website is so nice compared to other government websites I have visited that it actually looks like someone in the private sector created it!  Even the logo is cool!

The process to sign up to participate in ResearchMatch was simple and took me about 5 minutes to complete. Anyone can join too — many research studies are looking for healthy volunteers or “controls.”

Join today and spread the word and contribute to the greater good — https://www.researchmatch.org/

Woman Born With Half Brain Gives Everyone Hope – Michelle Mack An Inspiration For All Suffering From Brain Disease

CNN is reporting tonight on Michelle Mack, a woman born with half her brain who is leading a normal life!  According to scientists, her brain has re-wired itself!

This story took my breath away.  If someone can be born with half of a brain and live a normal life, then kids like Addi and Cassi who are suffering from a fatal neurodegenerative dementia disease called Niemann Pick Type C might be able to re-wire their brains if we can stop the degeneration from happening.

How about people who have Alzheimer’s and Parkinson’s — could their brains re-wire if the degeneration stopped?

Michelle Mack and family — thank you for going public and telling your remarkable story.  You give hope and provide inspiration to so many people who care about the brain.

Embed video is not working on CNN so here is the video link and story:
http://www.cnn.com/2009/HEALTH/10/12/woman.brain/index.html#cnnSTCVideo

FALLS CHURCH, Virginia (CNN)  — Michelle Mack has turned medical thinking upside down. The right side of Michelle Mack’s brain rewired itself to take over functions controlled by the left.

The right side of Michelle Mack’s brain rewired itself to take over functions controlled by the left.

Born with only half a brain, Mack can speak normally, graduated from high school and has an uncanny knack for dates.

At 27, doctors determined that the right side of her brain had essentially rewired itself to make up for function that was likely lost during pre-birth stroke. But her childhood and young adult years were fraught with frustration.

“It was very hard for me,” Mack said. “It was very hard for me growing up. No one knew the truth about my brain.”

Mack’s parents, Carol and Wally, realized shortly after her birth that something was wrong.

“There wasn’t a group to turn to,” said Carol Mack. “Michelle didn’t have cerebral palsy, I knew that. She didn’t have Down’s syndrome, I knew that. I had no place to turn.”

Ten years ago, Dr. Jordan Grafman, chief of the Cognitive Neuroscience Section at the National Institutes of Health, finally diagnosed the problem. Video Watch how Mack’s brain healed itself »

An MRI scan revealed she was missing nearly half of the left side of her brain. While it was clear Mack has some problems, Grafman said he and the family were shocked by the extent of the damage.

“We were surprised to see the extent of the lesion in her brain, which basically took away the left side of her brain,” said Grafman. “There’s some very deep structures remaining, but the surface of her brain, the cortex is 95 percent gone and some of the deeper structures, structures that control movement, are missing. These are all structures that are important for movement, behavior, cognition.”
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The only answer, Grafman said, was that Mack’s brain has rewired itself. The remaining half took over some of the essential functions that are normally done by the left, such as speaking and reading. That rewiring, however, came at a cost.

“Michelle has fairly normal language abilities, certainly basic language abilities, she can construct a sentence, she can understand instructions, she can find words when she’s talking, but actually she has some trouble in some aspects of visual-spatial processing,” said Grafman.

“It’s quite possible that in her learning, in her development, when the right hemisphere either took over or developed some of the language abilities that it cost her in some of the skills that are normally mediated by the right side of the brain,” added Grafman.

In the 10 years since Grafman first diagnosed Mack, she has seen some intellectual functions improve, the doctor said. Recovery has not been perfect, however. Mack still struggles with abstract concepts and becomes easily lost in unfamiliar surroundings.

The diagnosis explained why Mack had experienced a lifetime of difficulty controlling her emotions.

“He’s helped us understand the reason why I tend to throw fits, temper tantrums,” she said. “It was because I was missing half my brain.”

Mack will always have some problems, but dad Wally Mack said that Grafman’s diagnosis and treatment answered a lot of questions and gave him hope.

“Dr. Grafman explained that the right hemisphere is taking over, and it might take her a little while longer to get there with all the rewiring that has to take place,” he said. “But that told us all these bad days are behind us and there are nothing but good days ahead.”
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Michelle Mack is now 37 and lives with her mother and father. She works from home doing data entry for her church. She is fairly independent, pays rent and can do most household chores. She realizes she’ll need help for the rest of her life but wanted to tell her story to make it clear that she is not helpless.

“I wanted to do this so people like producers, photographers and security guards and police officers learn about people like me,” she said, “that I’m normal but have special needs, and that there are a lot people like me, so that they could be more understanding.”

Parents To Seek FDA Orphan Drug Designation For Cyclodextrin To Treat Rare and Fatal Cholesterol Disease

On Tuesday morning at 11am, Addi and Cassi are going to undergo volumetric CT scans of their livers and spleens.  The tests are being conducted by doctors to determine if the cyclodextrin IV infusion treatment the twins are receiving under compassionate use INDs approved by the FDA are reducing the size of their enlarged cholesterol filled organs.

UT Southwestern scientists have shown that Niemann Pick Type C mice organs can be restored to normal size through cyclodextrin treatment.  We are soon to find out whether the same is true for children who are afflicted with this rare and fatal cholesterol disease.

In all previous tests conducted on Addi and Cassi’s swollen abdomens, their spleens have measured about 12 centimeters. We are very excited and hopeful that they have reduced in size since starting the cyclodextrin infusions about 5 months ago.

We also received preliminary results this week that cholesterol is being excreted in Addi and Cassi’s urine and their lysosomes are getting smaller!  All positive signs and so far no negative side effects from the cyclodextrin treatment.  We are now infusing 2800 mg/kg over 8 hours 2x per week — we are getting into some significant doses.

Currently, my husband and I are working with a small core team of doctors and NPC parents to apply for Orphan Drug Designation for cyclodextrin (HPBCD). We intend to file our documents with the FDA in February 2010 and we are trying to get a pharmaceutical sponsor to help us.  If we are unable to secure a sponsor, we will sponsor the Orphan Drug Designation filing ourselves as private citizens.

Since no pharmaceutical company makes a sterile cyclodextrin infusion formulation, Adam our hospital pharmacist has to make Addi and Cassi’s formulation from scratch.  For the past few months, I have been working with a cyclodextrin manufacturer in Hungary and a US based cyclodextrin supplier who can help me make an endotoxin controlled cyclodextrin formulation that can be distributed to patients worldwide.  I hope to have a sterile compound available in 2010 for patients if all goes well.

Just for fun, I mocked up a little bottle (using Genzyme’s Cerezyme drug bottle) with a label.  We might be able to put our cyclodextrin into a plastic bag — essentially it would look like a bag of saline only it would have cyclodextrin in it.

Dysfunctional cholesterol metabolism has been implicated in the etiology of many diseases from  Alzheimer’s to Coronary Artery Disease.  It’s amazing to think that a non toxic food additive that is also the main ingredient in Febreze fabric freshener could be the next miracle drug and might be able to save my girls lives or give them more time with us.

Sign and Circulate Jamie Heywood’s Declaration of Health Data Rights Petition Today

Wired Magazine is running a great article about Jamie Heywood, co-founder of PatientsLikeMe, and his quest to make personal medical records electronic and easily accessible online.

Heywood is behind HealthDataRights.org, a movement to declare our individual right to have and share our health data. Heywood has started the Declaration of Health Data Rights petition and supporters can publicly endorse it by going to HealthDataRights .org. Essentially by having access to all the health data about ourselves in a timely (key word!!) manner we can make better health decisions and save lives.

I am one person who would happily share all of our medical records like Heywood proposes.  I have been looking into a way to try and opt-out of the Hippa law Privacy Rule requirements.  I am not interested in keeping our medical records private. In fact, I want people all over the world to access our medical records in the hopes that someone can help save the lives of our twin daughters who suffer from a fatal cholesterol disease.  In some cases my doctor’s can’t talk to each other unless I give written permission.

I am asking everyone I know to endorse the Health Data Rights petition today. Our family has literally spend hours collecting Addi and Cassi’s medical records from hospitals including Lucille Packard Children’s Hospital at Stanford, Mayo Clinic, Children’s Hospital Michigan, Children’s Hospital Oakland, National Institutes of Health and Renown Children’s Hospital.

You can see the picture of the 3 inch binders I have created that contain the most important medical information on Addi and Cassi (we have two each so far). The orginal stack of paper was two feet tall!  To get all of our data to doctors at various hospitals throughout the country, I have sent hard copies of the binders to them. If they requested the records themselves, they would have to sift through the two foot stack.  Do the top doctors in the world have time to do this?

Currently, we are six months behind in gathering all of the new records – it’s a constant battle as we try and keep up and request the records for two sick kids.  There is no reason why medical records could not be in electronic form and available to anyone at a click of a button to share and easily SEARCH.

At one point, we were going to scan all of Addi and Cassi’s medical records and put them online allowing any doctor or researcher in the world to access them.  We figured out quickly that it’s simply too time consuming to tackle and manage. When you’re trying to save your kids lives you don’t have time to send Hippa release forms to hospitals and weed through fax cover sheets and garbage that hospitals often send by mail. If someone is chronically sick and dying, trying to collect all personal medical records is virtually impossible.

As a society, we are living in fear of the health and life insurance companies and the issues surrounding pre-existing conditions. We need additional legislation with health and life insurance companies to make sharing electronic medical records a reality. We would probably save billions of dollars in productivity time as well.

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