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MABT5102A
Lisa428
Posted: Thursday, March 1, 2012 3:35 PM
Joined: 12/5/2011
Posts: 795


Hi to all,

 

I have posted this drug name before under monoclonal antibodies.  You can read what JAB told me about monclonal antibodies there.

 

I was wondering if anyone else was in this drug study??

 

If you or someone you know is, please let me know.  I'd like to compare experiences.

 

Thanks.

 

Peace and Hope,

Lisa


Lane Simonian
Posted: Thursday, March 1, 2012 9:28 PM
Joined: 12/12/2011
Posts: 4836


I don't know of anyone in this drug study, but would be interested in hearing more about your experiences if you wish to discuss them.

 

Amyloid plaques themselves are funny things.  Some people feel they are the cause of Alzheimer's disease.  Others say this cannot be true because every drug designed to lower their levels have failed to treat Alzheimer's disease.  The people who support the amyloid hypothesis say right target wrong drugs.  The people who oppose the amyloid hypothesis say they are either just a symptom of the disease or they are actually beneficial in providing protection against bacterial infections.  The really funny thing is that to a certain extent they are all right.

 

The real target in Alzheimer's disease should be a potent oxidant known as peroxynitrite.  The same pathway that leads to the formation of amyloid plaques leads to the formation of peroxynitrites.  Peroxynitrite formation contributes to the aggregation of amyloid plaques and amyloid plaques lead to the further formation of peroxynitrites.  If you prevent the formation of amyloid plaques (with phenolic compounds and Omega 3-fatty acids, for instance) you prevent the development of Alzheimer's disease.  If however, you reduce amyloid plaques once much of the damage done by peroxynitrites has occurred, you at best only slow down the progression of the disease.

 

Peroxynitrites contribute to the hyperphosphorylation of tau proteins and nitrate tau proteins inhibiting neurotransmissions, they oxidize glucose transport systems affecting energy and focus, they oxidize glutatmate transport resulting in toxicity to surrounding cells, they oxidize choline transport systems, the enzyme choline acetyltransferases, and muscarinic acetylcholine receptors resulting in a critical shortage of acetylcholine--a compound essential for short-term memory, they oxidize receptors involved in sleep, mood, behavior, alertness, social recognition, and smell leading to critical deficits or problems in all these areas, and they contribute to the influx of calcium which kills neurons and the release of glutamate which kills surrounding cells.

 

As many animal studies, a few clinical trials, and several case studies have shown the best way to treat this disease is not by removing the plaques (which again at best only slows down the progression of the disease), it is by removing the peroxynitrites with compounds found in various spices, essential oils, and other plant oils and by reversing part of the damage done by peroxynitrites with these same plant compounds.


Junipero
Posted: Tuesday, April 3, 2012 4:35 PM
Joined: 4/3/2012
Posts: 6


Hi Lisa -

My mom wil be interviewing for the MABT5102A trial in the coming weeks.  Her neurologist says she's an excellent candidate so we are hoping she gets in.  We've been told that there is reason to believe that this drug will work better than baupineuzumab (because it apparently targets a smaller, more toxic form of plaque).

Do you have any experiences from being in the trial that you could share with us?

Thanks!

Juniper


Lisa428
Posted: Tuesday, April 3, 2012 10:19 PM
Joined: 12/5/2011
Posts: 795


Dear Junipero,

 

Hello and Welcome to the AD/Related Dementia's Message Boards.  I'm sorry to hear about your Mom but I am very glad you've found us.

 

I'm not sure if I have any "words of wisdom" but I will tell you how it is going for me.  This is a long clinical trial.  If I'm not mistaken it's about 1.5 years.  The monclonal antibodies are supposed to attack the proteins that make the plaques.

 

I am on the drug.  I've been getting IV doses about every 3-4 weeks.  In between, I have blood work, urinalysis, EKGS, and MRI's done.  They, the clinic, also do neuropsychological testing to see how I am doing.  I have delined slightly but mostly holding my own (which to me is great).

 

I was diagnosed with EOAD in 2007 at age 53.  I will be 58 this month and I am still in the early stages.  I do follow "Best Practices"  which includes eating a health diet Meteattrian diet, daily exercise, brain/memory exercises, staying socially active (that part is hard for me) .

 

How are you doing?  And your Mom?

 

You may want to join an AD support group in your area.  They really help.

Also, we have a 24/7 toll free helpline.  You can speak with someone anytime if you need additional support.  800-272-3900.

 

Again, welcome.  You are not alone.  We are here.

 

You may want to start a new thread in the "Caregiver's Forum" too.  There are lots of wonderful people here on the boards who want to help.

 

Good Luck.

 

Thinking of you and your Mom.

 

Peace and Hope,

Lisa 


Junipero
Posted: Wednesday, April 11, 2012 4:29 PM
Joined: 4/3/2012
Posts: 6


Hi Lisa -

Thanks so much for the kind words.  We are doing OK.

We got the paperwork for the MABT5102A trial a few days ago, and we are a little shell-shocked about the number of procedures it involves over 1.5 years:

8 MRI's 

5 PET scans, some with contrast

2 spinal taps

~ 50 trips to the clinic for infusions

For anyone else with clinical trial experience:  do you think is this a particularly intensive trial or is this pretty much standard?  

 

Does anyone have experience with how their LO reacted to repeated procedures as part a trial?   Either positive or negative experiences?

 

Thanks,

Juniper


Inquiring mind
Posted: Thursday, April 12, 2012 12:25 PM
Joined: 12/3/2011
Posts: 8


Juniper,

That trial regimen sounds very similar to my wife's experience in the bapineuzumab trial.   She did not get the PET scans, but they were potentially on the table when the trial started.  All the rest sounds identical.


Lisa428
Posted: Saturday, April 14, 2012 10:37 AM
Joined: 12/5/2011
Posts: 795


Juniper,

 

I have not had any PET scans or spinal taps.  I don't think they are in my protocol.

 

Good Luck.

 

Peace and hope,

Lisa


Junipero
Posted: Friday, May 18, 2012 1:32 AM
Joined: 4/3/2012
Posts: 6


Hi all -  I just wanted to add an update for anyone else considering this trial.  There are two different trials in the US, one is a "biomarker study".  The biomarker study, we found out has many more procedures, including mandatory spinal taps and PET scans.

My mom balked at the biomarker study, there were just way too many procedures and trips to the clinic every two weeks.  Luckily, we found a different clinic nearby that was participating the other MABT5102A trial, and my mon will get her first infusion soon.

Lisa - I'll keep you updated as to our experiences once we get started!

Take care,

Juniper


Junipero
Posted: Friday, May 18, 2012 1:38 AM
Joined: 4/3/2012
Posts: 6


And, for Lisa and anyone else interested in this drug:

 

MABT5102A is now being called "crenezumab", and is all over the news this week because it's being tested in the Alzheimers trial in Columbia (Myriam posted about this).  But, I found this discussion of the difference between crenezumab and the other monoclonal antibodies.  See link below

 

http://www.alzforum.org/new/detail.asp?id=3156

 

"Q: How is crenezumab different from the other Aβ antibodies that are currently in Phase 2 and 3 trials?

 

A: We have a manuscript under review that describes its properties. Basically, crenezumab binds to oligomeric and fibrillar forms of Aβ with high affinity, and to monomeric Aβ with lower affinity. By comparison, solanezumab binds monomeric Aβ, and gantenerumab binds aggregated Aβ, as does bapineuzumab. Crenezumab binds all forms of the peptide.

 

Crenezumab is engineered on an IgG4 backbone, which allows it to activate microglia just enough to promote engulfment of Aβ, but not so strongly as to induce inflammatory signaling through the p38 pathway and release of cytokines such as tumor necrosis factor α. Crenezumab is the only IgG4 anti-Aβ antibody in clinical development that I am aware of. We have not seen vasogenic edema in our Phase 1 trials, which was the first main hurdle for us to overcome.

 

Q: Does that affect dose?

 

A: Yes. We can dose substantially higher than other anti-Aβ antibodies. For example, the bapineuzumab studies are dose-limited to 1 mg/kg as a result of vasogenic edema. Vasogenic edema resolved at 13 weeks. Hence, dosing for the Phase 3 was set at 1 mg/kg and 0.5 mg/kg once every three months in ApoE4 non-carriers, or 0.5 mg/kg in ApoE4 carriers. We are dosing as high as 15 mg/kg once a month. This generates a brain exposure that is between 10- to 100-fold higher. That is important.

 

By the way, one misconception along these lines warrants correction: Sometimes you read that solanezumab does not get into the brain, but bapineuzumab does. That is not true. Both get in at approximately a 1,000:1 ratio. In fact, most antibodies establish a steady-state ratio of approximately 1,000:1 blood-to-brain, unless they are uniquely engineered to cross the blood-brain barrier.  

 


Mimi S.
Posted: Friday, May 18, 2012 8:08 AM
Joined: 11/29/2011
Posts: 7029


Just a comment re tests to be used as biomarkers. These are the ones that use the Pittsburg compound PET scan and spinal taps.

One goal is to get diagnosed early, before there is a lot of damage to the brain.

 

From lectures I have attended showing results of such testing on a supposedly normal population, I get very excited about the possibilities of finding the disease as early as possible. 

 

It seems that the first evidence of the disease shows up in a spinal tap. And that would be the best time to start treating it.

 

Thus, if you are able to participate in one of those clinical trials, it would be great.

 

I was diagnosed a year earlier than Lisa and am also still in the Early Stage. I likewise am a firm believer in the Best Practices. I am convinced that is the best we have right now.  But I wonder, what would have happened if I had been diagnosed when I first became aware of symptoms, probably five years earlier?