Friday, August 15, 2008

FTY720 may be a novel treatment against chronic viral infections

Just when I seem to be having a really hard time claiming my stake (or steak?) in the extension phase of the Fingolimod Phase III trials, out comes even more great news about the drug.

It seems that researches infected some mice with the mouse form of meningitis and, after 3 days of administering low doses of FTY720, the infection was cleared up. This is phenomenal news as they are discussing possible future trials in Hep C and AIDS patients.

Apparently the war your body wages against viral infections is usually fought in the lymph nodes. This happens to be where Fingolimod sequesters T-cells in order to prevent them from circulating and attacking myelin in MS patients which is why I've not had an MS flare in well over a year.

With the T-cells sequestered in the lymph glands, I guess there's more of them available to fight against the viral infections that try to replicated in the lymph nodes.

I don't pretend to understand it all, but it sounded like good news to me when I read the article that came out the other day.

Here's a recap of it:

London, Aug 14 (ANI): Researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found that trapping disease-fighting white blood cells (WBC) in the lymph nodes might be a novel strategy against chronic viral infections, such as hepatitis C and HIV/AIDS.

Senior author John Altman, PhD, associate professor of microbiology and immunology at Yerkes Research Center and Emory University School of Medicine, said that the discoveries are based on the study of two varieties of a virus that causes meningitis in mice.

Standard black laboratory mice can fight off infection by the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but are vulnerable to chronic infection by a variant called clone 13.

Altman and his colleagues found that infecting mice with the Armstrong strain sequesters white blood cells in the lymph nodes, while clone 13 does so less stringently.

Our hypothesis was that if we could artificially induce conditions like those produced by the Armstrong strain, it would help the immune system clear an infection by clone 13, Nature quoted Altman, as saying.

The researchers turned to an experimental drug called FTY720, which prevents white blood cells from leaving lymph nodes.

FTY720, also known as fingolimod, desensitizes white blood cells so they can't respond to the chemical messenger sphingosine-1-phosphate (S1P).

S1P also influences heart rate and smooth muscle contraction in the airways.

Altman said that the scientists had previously thought of FTY720 as something that suppresses the immune system.

While not approved for sale by the FDA, doctors have tested it for the treatment of multiple sclerosis and preventing kidney transplant rejection.

The researchers found that even if mice have a stable chronic LCMV clone 13 infection, treatment with FTY720 can still improve their immune response against LCMV enough to have them rid it from their systems.

FTY720 appears to prevent exhaustion in the group of white blood cells called CD8+ T cells, which are responsible for killing off other cells that become infected by LCMV.

Altman said that usually, the stress of infection kills some CD8+ T cells and leaves others unable to respond to the virus.

He said that it is unclear whether FTY720 resuscitates non-responsive T cells or allows new ones to avoid being killed off.

Thursday, August 14, 2008

It's always the things you least expect

...that end up throwing the monkey into the wrench (or however that saying goes).

Today was supposed to be the ho hum, normal skin exam at dermatologist day. It's the very last test needed to complete my one year study and allow me entrance into the extension phase.

Of course it's located in Jacksonville which is a 2 hour drive, but luckily the appointment wasn't until 11am so there was no need to get up at the crack of dawn or anything. I left here at 9 and had a nice ride all the way up except for a little rain. It was so uneventful I worried I may have to pull over and catch a few z's because the monotony was bringing on fatigue.

Then a truck changed lanes and cut me off and I had to slam on the breaks. I was good to go, all juiced back up from adrenalin and never had to pull over to rest. I ended up 20 minutes early for my appointment.

After reading all the jokes in the new Reader's Digest I brought along, a nice nurse poked her head into the waiting room and said "Jeri?"

I followed her back to the exam room which had a chair, a table, and some weird looking equipment I can't even describe. She told me to undress down to undies and bra and sit on the table with the paper towel she called a "sheet" covering me.

I waited and waited and waited. I got really cold and just as I was seriously contemplating putting some clothes back on, a knock came on the door.

The doctor and her nurse entered. It's not the same doctor as last time because last time the doctor was a man. He had looked me all over and said there was nothing I should be worried about and he even let me show him a couple of bumps on my head that I've always wondered about. They were "nothing" as well.

This time, the doctor came in and walked around to the opposite side of the table from where I was sitting, so she was behind my back.

"Uh oh. I can see right now I want you to lie down on your tummy because I see a couple things I want to take a closer look at."

"You mean that skin bump on my back?"

"No, that looks fine, it's nothing. I see a couple really dark moles that are overlapping."

So I lay down and she turns on the spotlight above me. I guess that's supposed to make me hold still like a deer in the headlights or something.

She whips out a Sharpie from her coat pocket and proceeds to play Connect the Dots on my back, drawing circles around the "suspicious lesions".

She utters the words I had no idea I would hear and thus had not even sufficiently worried about: "I'd like to biopsy those."


"Well, they're dark and irregular and are the kind of mole that could turn into skin cancer somewhere down the road. Doesn't mean they are now, but by biopsying them we get rid of them whether they are or aren't and you have the peace of mind that knowing everything is fine."

"I've had those moles ALL MY LIFE! Didn't the last doctor say anything about them?"

The nurse shuffles through the file and says "Yes, Dr. ___ did note them when he saw her last year."

To which the fine doctor replied, "Well, that's him. I'm sort of known for being the Biopsy Queen around here. I like to be better safe than sorry."

So, she has me turn over and she finds yet another reason to draw a one-eyed, mouthless smiley on my stomach. A tiny dark brown dot of a mole that I know has been there for quite a few years, and it's also noted in the file.

"Um, why are you circling that one?"

"We're going to biopsy it, too."

"It's just a speck. Once you have biopsied it, it'll be gone."

"That's the plan," She smiles.

The nurse pipes up saying "what kind of insurance did you say you have?"

"I didn't." I said, "I am hear being seen as part of a research study and the drug company is paying for everything."

"So are they going to pay for the biopsies?" she asks.

"I am SURE they will since it's their idea that I need to come see you and have my skin monitored anyhow. If you find anything to cut off, I'm pretty sure that's part of the deal. They'll pay."

"Well," says a skeptical nurse, "we'll need confirmation from someone in charge."

I tell them to call the Research Department at Shands Jacksonville. They make me wait there lying on the bed with that little paper towel for a sheet. The nurse comes back and says "we can't reach them. If we don't find out something in the next few minutes we are going to have to schedule for another day as we have a backlog of patients to see today."

In my head I am sighing a gigantic sigh of relief. I have not yet sufficiently worried about the ramifications of all this or how painful a biopsy or three might be. I need to go home and work up a good tizzy first that I can talk myself back out of.

So I leave and I am driving home. About 10 minutes out of the parking lot something makes me pick up the cell phone and just SEE if anyone called my trial coordinator.

She was surprised to get my call and even more surprised when I explained the situation, because nobody ever called her. She said she had gotten 2 calls earlier and when she answered the second one she asked them to hold, which they agreed to. When she came back, they were gone and no message had been left.

"So, these are new moles since your last visit?"

"No, it's just a different doctor who apparently likes getting her quota of $150 biopsies with every new patient she sees."

"So, she thinks these are cancerous lesions?"

"No, she thinks they probably aren't. But a biopsy of each one will leave no doubt."

When I tell her they won't do it until there's some guarantee of payment, she tells me to call them back and give them her cell and pager numbers and tell them it's imperative that I get the biopsies done today.

"In the meantime, I will call the Sponsor and make certain they are aware of this new development and that they are going to agree to pay."

So I find a parking lot to sit in and I try calling the dermatology place. I get a big run around about how she's only an operator and that I need to know a name or an extension. Luckily I remembered the doctor's name. I get put through and get voice mail.

I leave a big long message about how I need to have the biopsies done STAT and that I can turn around and drive back right now (which, in hind sight is what I should have done) and here's all the ways to get a hold of Research and they will verify that Novartis is going to fork over the payment.

I never got a call and neither did the trial coordinator. She called me at 4pm to say that she has been trying all day to get through and keeps getting a busy signal. If not a busy signal then a message saying "we're sorry, all circuits are busy at this time, please try your call later." What the heck?

I spend the rest of the day hitting redial on my cell phone trying to get through as well.

I am highly suspicious that the fact that American Idol is holding next season's auditions in downtown Jacksonville has something to do with the phone circuits being overloaded. The thousands of calls to back home saying "they don't know talent when they see it and Simon's a great big JERK, Mom!" are clogging up the phone lines and preventing people who have issues like MS and cancer and research and other things from actually having any meaningful conversations with those who might hold their futures in the balance.

I finally got through, tho. It was 5:10pm. A lady with a really nice voice told me the office was now closed and if this was an emergency to hang up and dial 911. Figures.

So, here we are. Thursday evening and the results of my MRI have never been okay'd by Berlin, so there's no way the Monday ext. phase was going to happen anyhow.

Here's the new clincher tho. Novartis, upon hearing of the biopsies that need to be performed, are now saying that my ability to even continue in this study at all now rests solely upon the results of the biopsies of these three stupid dark dots on my skin that I have had all my life.

If that ends up causing them to take my beloved Fingolimod away from me, head's are going to roll. Starting with the Biopsy Queen, I think.

Tuesday, August 12, 2008

I'm still shaking with excitement!!

I got the most exciting phone call earlier! It was my trial coordinator. I had called this morning and left her a voice mail asking if she had scheduled my dermatology appointment yet. Of course I was confused about how we left things -- whether I was supposed to call them directly or if she was going to set it up for me. Naturally, I was supposed to call myself. Oh well.

When she called she said she would hang up right then and get it scheduled and call me back.

When she called back she asked how many shots I had left.

"3" was my answer.

"How many pills?" she quizzed.

"Let me go get the bottle and count them, hang on. 25" was my reply.

She said my appointment with the dermatologist is this Thursday at 10:50. Then came the exciting part.

"I was thinking about this and if Berlin says your MRI is good and does not have to be redone, then after your dermatologist appointment everything will be done."

I said "Yes....??"

She said, "Well, then if Berlin says it's okay to move to extension phase, rather than wait until Sept. 3, we can do it next Monday instead."

I paused while it sank in.

"Are you still there, Jeri?" she asked.

"Oh YES! I'm still here! Just trying to believe what I'm hearing. You mean NO MORE SHOTS??!!"

She laughed her beautiful lyrical laugh and it rained over me like a soothing salve. "Yes, that's exactly what that means."

So...I'm not getting my hopes up, but my fingers are crossed, as well was my toes. I'm saying a little prayer that my MRI was good to go. It turns out that it doesn't matter WHAT it shows, just as long as the images were taken according to protocol.

I'm guessing that they were because the MRI technician (after peeling my keys off the tube and taking my dead ATM cards to the locker for me) told me that they were going to take a while because since I was in the clinical trial, they had to be done a certain way. That tells me that she was aware of how she had to do them even if she wasn't aware that my ATM cards should not go in the tube with me. Hopefully she got the important part right.

Thank goodness I took pictures while doing my last shot. I wanted to show a friend of mine how big the needle was.

Here's the last one...hopefully forever:

That's not easy to do one handed. Usually I'm grabbing my thigh and pinching up a big roll so I can trick myself into believing the needle won't come anywhere close to my bone if I do that. Just sticking it in with one hand while watching through the camera I was holding with the other was a really strange experience. It was like watching on TV and I wanted to look away but remembered that I really had to watch if I wanted to do it right. No changing the channel.

So, I hope I'm not speaking too soon and jinxing myself here, but that, folks, might be the last time I ever stuck myself with a needle. Ever.

I'd say "pinch me! I'm dreaming!" but it might feel too much like a shot and scare me.