A possible delivery system that crosses the blood-brain barrier!!!!

Kyle’s mom and I are off to get the researchers’ opinions of this hopeful breakthrough! 

University of Iowa scientists use blood-brain barrier as therapy delivery system
Enzyme delivered through the bloodstream corrects deficiencies in the brain

The blood brain barrier is generally considered an obstacle to delivering therapies from the bloodstream to the brain. However, University of Iowa researchers have discovered a way to turn the blood vessels surrounding brain cells into a production and delivery system for getting therapeutic molecules directly into brain cells.

Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases.

The findings, which were published Sept. 13 in Nature Medicine’s Advance Online Publication (AOP), could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases.

“This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain,” said lead investigator Beverly Davidson, Ph.D., UI professor of internal medicine, neurology, and molecular physiology and biophysics. “This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases.

“In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons,” she added.

Lysosomal storage diseases are individually quite rare, but as a group they affect approximately 1 in 8,000 live births. The diseases are caused by deficiencies in enzymes that break down larger molecules. Without these enzymes, the large molecules accumulate inside cells and cause cell damage and destruction.

Enzyme replacement therapy has been successful in treating one form of lysosomal storage disease called Gaucher disease. However, storage diseases that affect the central nervous system remain untreatable because it has not been possible, to this point, to get the missing enzymes past the blood-brain-barrier and into the brain.

“Our discovery allowed us to test the idea that the brain cells might be able to make use of the reintroduced enzyme to stop or reverse the damage caused by the accumulated materials,” said Davidson, who also is the Roy J. Carver Professor in Internal Medicine. “In the treated mice, the affected brain cells go back to looking normal, the brain inflammation goes away and the impaired behaviors that these mice have is corrected.”

To develop their gene therapy targeting system, Davidson and colleagues used a technique called phage panning to identify peptides that hone in on the blood vessels surrounding the brain. Surprisingly, they found that peptides that targeted the brain blood vessels in mice with lysosomal storage diseases were distinct from the peptides that targeted brain blood vessels in healthy mice. Moreover, the peptides that targeted blood vessels in different diseases were distinct from each other, suggesting that each disease causes specific alterations to the blood vessels.

The team modified a deactivated virus used for gene therapy so that the virus expressed copies of the unique brain-targeting peptide on its outer coat, and also carried the genetic blueprint for the missing enzyme.

The study showed that the modified virus targeted the blood vessels in the brain and caused the blood vessel cells to produce the enzyme. Most importantly, the researchers found that the enzyme was secreted into the brain tissue in sufficient quantities to correct the disease symptoms and problems.

The team was able to use this approach to treat two types of lysosomal storage disease in mice, suggesting that the approach could be used for other types of lysosomal storage disease and possibly other neurological disorders.

Thank you, Debra!

Just like my friend, Heather, and her husband, Jim, helping us raise money for Hannah’s fight (Makdan publishing), my friend, Debra, has offered to donate 30% of all sales of her absolutely adorable teddy bears and stuffed animals for Hannah’s cause!

For my Canadian friends, please take a moment and consider Bears N Buddies.  She has been around for awhile, and she has such a huge heart.  She donates often to causes she cares about, and I want to thank her and support her anyway I can!

See the cute teddy bears and stuffed animal kits!  Thank you, Debra, for everything!

Ethan M, 23 months old with Gaucher’s type 2

This is a guest post from Tina M. from Kansas City, Missouri.  She is the mom of Ethan, 23 months old, recently diagnosed with Gaucher’s Type 2.  

When we found out that we were having a little boy, we were ecstatic. The pregnancy was going great. We had no complications until we hit the seven month mark. Then the complications started, and haven’t ended yet. Ethan James McKown was born at 33 weeks. He was 4lbs 2oz and 19inches long. He was a little guy, but we knew right away he was a fighter. He did well in the NICU for 3 weeks and we finally got to take him home on the forth of July 2007.

He always had large stomach but all the doctors in the NICU just simply said “he just has a large belly” and left it at that. We thought it was peculiar but we were so stressed with everything going on in the NICU that we didn’t think much of it at the time. Eventually he would grow out of it, right? We were wrong.

He went through a period where everything seemed to be getting back to normal. He started to get bronchiolitis/ bronchitis with severe double ear infections. We were fighting off every little cold and sniffle he would get. There was one night that we thought we were going to lose him. We knew he had a cold and we had taken him to his pediatrician and he gave us some cold medicine and said to keep and eye on him.

A couple of nights later we put him to bed and notice that he just wasn’t breathing right. We picked him up and tried to get him to respond to us or “liven” up a bit. He just looked at us exhausted, working very hard to breathe. When we couldn’t get him to keep his eyes open or breathe normally we decided we better take him to the ER. We went to the local hospital and it was a nightmare! They are not equipped to deal with a child that fragile and that little.

He was still very petite. Every nurse and every doctor in the ER were in that room. They did chest X-ray’s and everything else and finally made us leave the room because they had to put a breathing tube in. We were torn apart. Even the security guard who escorted us to the waiting room had tears in his eyes. We thought we were going to lose him. We called both of our parents at 2am and told them what was going on and sat and waited. The longest thirty minutes of our lives past by and we were finally allowed back to the room. He looked so helpless and completely drained of everything. The hospital had called for a transport to the area children’s hospital because they didn’t have the equipment to handle Ethan.

The children’s hospital was about a forty-five minute drive away. We got to the children’s hospital and were immediate reassured everything was going to be alright. We were in very good hands then. They admitted him to a room and he had a bad case of bronchitis and the flu on top of it. His poor little body couldn’t keep up but he sure was fighting hard! We were there for about a week and were released to go home.

Over the next 6 months or so we were in and out of the hospital at least once a month with respiratory issues, lack of weight gain, and various other issues.

Finally in April 2008 they admitted Ethan for failure to thrive and said that he wasn’t leaving until they found out what was wrong. They ran hundreds of tests in the week we were there. They first thought he had Cystic Fibrosis, but that test was negative. They drew more blood and finally told us we could go home because they would have to wait on results from some of the tests.

A week or two after we went home, we received a call stated plainly that we had an appointment in genetics the following week. That was it. No explanation, no reasoning, nothing.

May 5, 2008 two days after my husband’s 25th birthday our lives change forever. We met with Ethan’s genetics doctor and counselor and learned that he had Gaucher Disease. We had never heard of it and had no idea what we were up against. I have never felt so helpless or heartbroken in my life. They weren’t sure which type he had, but since he presented symptoms so early and already had neurological side effects, they were leaning towards type II but were hoping for Type III.

The next week he went into surgery to get a port placed so he could receive enzyme replacement therapy. We had quite the scare when he had trouble breathing after the sedation. About three weeks later, we received the results from his Type testing. While we were in the hospital with pneumonia, we found out that he had a homozygous L444P mutation. He had type III. We were so happy we cried that day. There was a chance for him. He would at least get treatment and hopefully live a healthy happy live. He was doing well with his treatments and everything was starting to get on track. He still wasn’t gaining weight, but his levels were good. Everything seemed to be looking up for us.

I went to visit my brother in Topeka, KS which is about an hour away. Ethan would have breath holding spells, but none were as bad as that night. He went into a fit while grandma was feeding him. I took him from her and he stopped breathing. I immediately started CPR and tried to get him back. My brother called an ambulance but I luckily got him breathing again before they arrived. That was the longest three and half minutes of my life!

After this episode, they scheduled a sleep study and realized that it was very dangerous for him to sleep. He would wake up about twenty times an hour because he would stop breathing. He was only getting two minutes of REM sleep a night. It was no wonder he wasn’t gaining weight. He was burning calories even when he was trying to sleep.

After seeing the results, the ENT clinic said that it was probably a good idea to have a tracheostomy tube put in. We were completely caught off guard with this. We didn’t know what to say but we had no choice. The risk of our son dying in his sleep was too high; we had to do the surgery. The scheduled it for the following day. They also did a surgery on his eyes to fix his strabismus.

When we saw him in the ICU after the surgery, I wanted to scoop him up in my arms and just go home. All we knew was our son was laying there with a tube in his throat to breathe through and blood filled tears. It was the most heart wrenching sight. He looked at us so confused. He couldn’t figure out why he couldn’t call out to us. He was trying to talk but no sound was coming out. His eyes would fill with tears which just made it worse. It is so hard to know that we won’t be able to hear his laugh again. We miss that more than anything.

He spent five days in the ICU and then another week on a floor before we were trained enough on how to take care of him.

A week before Christmas 2008, we went home and turned his nursery into a hospital room. We have oxygen sensors, liquid oxygen tanks, suction machine, CPR equipment, humidification machine. The list goes on. He started sleeping better and finally began to put on some weight, but not much.

In March of 2009 we had a gastrostomy tube placed and a nissen fundoplication because his acid reflux was so bad. He started to consistently gain weight and was doing better.

In April of 2009, they decided to send our blood off for more genetic testing because he was not responding to the treatments like a typical Type III patient would. We received the results a few weeks later. The results were not good. Ethan in fact has one copy of L444P gene and one copy of L444P, A456P, and V460V:1497G>C gene. His genetics doctors have never seen this variant of the disease before.

Ethan has Type II Gaucher Disease. Our world has changed forever. We just found out that our son probably will not live to see his third birthday.

We will be forced to stop his enzyme replacement therapy and he will slowly begin to fade away from us. We cannot understand why they will not allow us to continue the treatment when it seems to be doing him good. Why must they give up on our son?

If you want bi-weekly Hannah updates via email

I have had a few people ask if I could put something together where they didn’t have to visit the blog all the time to get updates on Hannah.   So I am putting together an email list for those of you who want me to email you an update on what is going on with Hannah every 2 to 3 weeks.  If you are interested, just add your email below!

Hannah’s Bloggy Giveaway Winners!!

Over 100 entries to Hannah’s Giveaway, thanks to these wonderful donations!  If you are a winner, please email me with your details (address, email, etc.) so I can get your prize delivered to you!!

• Children’s book (signed by the author) - #110 Lily K
• $10 Barnes and Noble card - #34  aikjane
• Blog Makerover by FlibbyPie Design - #42 Petula
• Three Digital Scrapbooking Kits ($18 value) by designer Chris Wasielewski – #29 Carolsue
• “Breathe” Necklace/Earring Set by Hammi Jammi Jewelry  - #67  Charlotte R
• Any item from the Last Day of Forever Designs by TwilighterVA store (with the exception of 25-piece and 40-piece charm bracelets) – #16 Celeste
• Gratitude Candle Collection from Soy4Me - #100 Cristina 
• Slendertone Muscle Conditioner ($179 value) from Accidentalmommies.com - #76 Sherry G
• Choice of any 12″ x 16″ photograph print ($20 value) from Picture Perfect Too - #95 Estela S
• Bratz for Wii game from SaveYourMoneyMama - #50 Melissa V

 Thank you all for participating!!!

Please, please vote for my “support”

TheProjectCharity.org, as many of you know, is a new organization that was created by an amazing woman, Nicole Boice, to help parents just like me find support, resources, and valuable information when dealing with rare diseases.  As all of you know, I have had a helluva time trying to find anything, as I have felt so much on my own.  That’s why I have joined TheProjectCharity.org as a parent mentor and have been working with them to get going.  This is MY contribution to the rare disease community, something that will reach out to thousands of families so they don’t feel “lost.”

Please vote for TheProjectCharity.org.  You don’t need to submit an email, address, or any information.  Just a click.  Vote every day until March 31st.  This means so much to me.  Please just give US a click.

VOTE HERE!  (more details)

Hannah’s Facebook Cause – almost 1000 members!

I would have never believed Hannah’s Facebook Cause page would have grown so fast! We have over 930 wonderful people believing in our hope to find a treatment for Hannah to save her life. Thank you so much! If you haven’t joined yet, just click below – we’d love to have you!

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