Trofinetide #3

trofinetide1And on we go! So far I’ve discussed what Trofinetide is, how it came about and what it does. Great, but what are we talking for a timeline, right? Who holds the strings? Just what the heck are the steps to get it to our kids! Note: This is pretty lengthy and may be boring to some, but I thought it important to put how long we all feel it is taking into perspective with how long it could take!

Well, some of those steps are already completed. There was an initial trial, Phase I, of a very small number of adults, I think it was 10, to make sure the drug was safe. It was very short, you can read about it here. That was completed in 2012.

Next came Phase II. This was begun in 2013 and completed in 2014. This was a much larger study, with 53 participants ages 16-45 (Katelin was participant #26 and was either the last or next to last to receive the lower dose of 35mg/kg or placebo; the higher dose was 70mg/kg) You can read about this phase here.

In between these two phases, something very important happened. Neuren Pharmaceuticals was granted “Fast Tracked” status for NNZ-2566 (later named Trofinetide) So, what’s the big deal about that? Quite a bit, actually. The FDA can grant Fast Track status to a drug that is developed to meet an unmet need for a serious illness/condition. There are multiple advantages in having been given Fast Track status-

From the FDA website:

A drug that receives Fast Track designation is eligible for some or all of the following:

  • More frequent meetings with FDA to discuss the drug’s development plan and ensure    collection of appropriate data needed to support drug approval
  • More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
  • Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
  • Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

The end result being:  The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.

As you can see, this is a fantastic designation. However, there is also another designation that NNZ-2566 was given in 2015-Orphan Drug Status. While this doesn’t directly affect the timeline, it gives great incentives for companies to continue the development and trials necessary to get the drug to market. Without these incentives, it becomes more likely that a company would not see the possible profitability as a reasonable risk. Trofinetide has also been granted Orphan Drug status by the European Medicines Agency (EMA).

There is a third designation- Breakthrough Therapy status- that Trofinetide did not receive, though Neuren applied. You can read all about my thoughts on that, here. If we were in person, talking face to face, you and I, I would have to say “don’t get me started on Breakthrough Therapy status!”

In the end, though, being Fast Tracked is the main thing. So, you ask- it’s taking FOREVER, it doesn’t seem very quick to me! But, really it is. It’s been only 6 years from the time of the first phase. We are now looking at, very shortly, the third and final phase. If you were to look at the FDA’s website about clinical trials you would be aghast at how long and how many participants are generally included.

FDA: Phase I: Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.
Length of Study: Several months (approx. 70% of drugs move on to next phase)

NNZ-2566: Study Participants:10 Length 5 days

FDA: Phase II: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years (approximately 33% move on to next phase)

NNZ-2566: 53 participants Length: 6 weeks/participant; Phase IIb (Pediatric phase) 82 participants Length: 11 weeks/participant; less than one year each, overall

FDA: Phase III Study Participants: 300 to 3,000 volunteers who have the disease or condition
Length of Study: 1 to 4 years (25%-30%) move forward.

Trofinetide: Phase III; I haven’t heard anything yet about how MANY participants there needs to be, but from everything I’ve read and heard about the trial will be 6 months/participant; less than one year overall.

Now, if Rett syndrome trials had the same guidelines applied it would feel like eons! Imagine getting several hundred participants just for the Phase II! and 3,000??? never. And look at the percentages that progress! Say 100 drugs start out in Phase I, 70 move on to Phase II, only 33% of 70 move on; that’s approx. 23. What happens after Phase III? only 25-30% of those 23 move on; that’s approx. 6. Now, there’s no doubt in my mind that Trofinetide will be one of those 6, but really it’s beating tremendous odds here, both in timeframes and probability.

Ultimately, the FDA holds the strings. Luckily, with Fast Track status, any questions/problems/concerns can be addressed while this third trial is ongoing, without it Neuren could get to the end of the trial and the FDA goes “oops, we don’t like the way you did this, do it all over.”

Fairly soon the call will go out for participants. Hopefully, there will be enough sites open in the States and abroad to fill all the necessary spots quickly. Let’s do it, folks. is there to help with expenses; I for one will open my home to any family if they have a site in LA and/or San Diego (which would be a bit of a drive, but I have a pool and hot tub 😉 ) We can do this!








Posted in boys with Rett syndrome, breakthrough therapy, FDA, hope, margaret brimble, Neuren Pharmaceuticals, NNZ-2566, Orpan Drug Status, orphan drug designation, Rett Syndrome,, Trail to a Texas Trial, Trofinetide, Trofinetide Pediatric trial, Trofinetide Phase III, Uncategorized | Tagged , , , , , , , | 17 Comments

Trofinetide #2

trofinetide2So, here we go- Why was Rett syndrome chosen for Trofinetide trials. Contrary to what most people think, Trofinetide was not developed for Rett syndrome. A quick google search reveals that it was first developed for stroke, but the focus seems to have quickly changed to TBI.

The US Army, in conjunction with Walter Reed Army Hospital, funded initial development for NNZ-2566 (Trofinetide) Here is an excerpt from the Intrepid-2566 website (It’s no longer up now that the trial is over)

“Over the past 10 years, the incidence of traumatic brain injury (TBI) experienced by armed forces personnel  in the conflicts in Afghanistan and Iraq has increased significantly over that seen in previous wars.  TBI is a leading cause of battlefield death and long term disability.  It is estimated that upwards of 60%* of all combat related casualties that are admitted to Walter Reed Army Medical Center or Bethesda Medical Center may be suffering from some level of brain injury. Increased attention and funding has been given to ways of protecting service members from TBI, to improving medical care and resources for recovery following a TBI, and for research into new drugs and other approaches to treat TBI.  To advance the care and treatment of TBI patients, the military conducts research and collaborates with many public and private organizations to investigate the potential usefulness of new medicines to improve recovery. NNZ-2566 is one such drug and in addition to the early work on NNZ-2566 that was undertaken by scientists at the US Army’s research laboratories, the US Army has further supported the testing of this drug in TBI by awarding two grants to help complete of the INTREPID-2566 study.”

This study ended after 10 years; while it had no effect on mortality, those that received NNZ-2566 and survived were better off than those that did not. As I recall there were limitations that were discovered during this trial, by that I mean factors that were found which impacted the effectiveness of NNZ-2566 and this is why trials are so necessary. First, the dosage was miniscule compared to what is being used in trials today. Secondly, it was given by IV, this caused dilution and because most patients were given diuretics, the medication was flushed out of their system. Thirdly, even though the trial was double blind, the control group had less severely affected soldiers than the drug group. You can read about the trial-here.

Meanwhile, Autism came up on the NNZ-2566 radar. And here comes the crux of why Rett syndrome and Fragile X are the two disorders currently being trialed with Trofinetide. There are two aspects (there may be more, but these are the two that are obvious and are easy to explain) of Trofinetide that are the foremost reasons why it might be helpful in Autism and Autism Spectrum Disorders.

Autism has been linked to inflammation in the brain and Trofinetide has anti-inflammatory properties. However, the real key, imo, is in the dendrites of nerve cells. Dendrites are the fingerlike, out-branching extensions of nerve cells. They act sort of like a telephone line conference call- receiving information and relaying it to its cell’s body and then out the other side to the next cell. The space between each cell’s dendrites is called the synaptic space. Trofinetide has been shown to normalize the number and length of dendrites. The length and number of dendrites is affected in autistic people. There are two subsets of this example. One in which there are too many dendrites and one in which there are too few.

In this video of a lecture given by Dr. Snape, he goes into how Rett syndrome and Fragile X mimic these two subsets; Rett syndrome representing the “too few” and Fragile X representing the “too many” subsets and are therefore the optimal trial subjects. These are essentially control groups for autism. This is a phenomenal discovery. Not only are the disorders themselves control groups, but given that Rett syndrome occurs primarily in females and Fragile X occurs more often in males, the trials are also gender specific and so are also controls for gender as well. And that is how and why Rett syndrome became one of the two disorders that were chosen to trial!

Given these two major properties of Trofinetide (anti-inflammatory for the brain and normalizer of dendrites) it is easy to extrapolate the number of disorders that may benefit from its use.

Next week…what are the different FDA designations assigned to Trofinetide and what they mean for our children.


Posted in boys with Rett syndrome, cure, Fragile X, hope, Intrepid 2566, Neuren Pharmaceuticals, NNZ-2566, Rett syndrome Awareness, TBI, Trail to a Texas Trial | Tagged , , , , , , | Leave a comment

Trofinetide #1

So, we are narrowing in on the start of Phase III of Trofinetide. It’s a word that causes caution, skepticism, hope, giddiness and a myriad of other emotions. Even though I am completely convinced of it’s effectiveness, how it affects each person is still unknown. That’s the scary, yet tremendously exciting unknown. But what IS it.

This is Trofinetide. (read Neuren’s indepth description)

all following excerpts are taken from the above page.

“Trofinetide is the name proposed by the World Health Organisation for our lead clinical-stage drug candidate (previously designated by Neuren as NNZ-2566). It is an analog of a molecule which is derived from IGF-1 and occurs naturally in the brain. IGF-1 is a growth factor stimulated by growth hormone. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical both for normal development and for responding to injury and disease.”

So, here we have the IGF-1 protein showing the portion of it that was modified and comprises Trofinetide.


Trofinetide (initially known as NNZ-2566 was discovered by Margaret Brimble’s lab. Margaret Brimble is a world renown researcher with multiple awards under her belt, lest you think this is her only achievement. Not by a long shot!

But, let’s cut to the chase, what does it actually do?

When speaking to someone about Trofinetide, I usually use this visual…take your hands, open them and hold them close so the finger tips are almost touching-that’s the normal brain, before Rett syndrome. The space between is called the “synaptic space”, the distance a signal has to jump from one nerve cell to another. Now, make a fist. That space is now HUGE and not only that, the “fingers” are gone. This is the Rett brain. Now, reopen your hands, that’s what Trofinetide does. But here you go, from Neuren’s site.


This is surely simplified, even I know that. There were so MANY hurdles to overcome. One of the main ones-breaking the blood/brain barrier, I’m not a chemist so I doubt if I would comprehend the fundamental basics of how it was done, but since I’m not a chemist, I don’t care. (Sorry, Margaret) But, if a picture is worth a thousand words, this picture will one day be worth a million words and more.

Next week… why were Rett syndrome and Fragile X chosen?



Posted in boys with Rett syndrome, Communication, cure, Fragile X, hope, margaret brimble, Neuren Pharmaceuticals, NNZ-2566, Rett Research, Rett Syndrome, Talking, Texas Children's Hospital, Trail to a Texas Trial, Trofinetide | Tagged , , , , , , | Leave a comment

Here’s to a New Year and a New Hope

This will be my last post of the year!


Katie swinging blog post

Katelin swinging and sweating in Texas

I’m feeling particularly retrospective at this time, this year. Facebook has reminded me on an almost daily basis since November of Katelin’s participation in the Adult trial (Phase II of NNZ-2566, now Trofinetide) I have been able to skip down memory lane in a way that wouldn’t have been possible without the technology in place today.


I’ve rewatched and reread our journey, day by day. It really seems impossible to believe it’s been four years already and that soon we’ll be moving on to Phase III. I’ve watched her draw her circle, I’ve lost count how many times. I watched her pour paint, I remembered it, but had forgotten that I caught it on tape. lol, tape. I’m dating myself. And, I relived again her regression afterwards. I’m glad she doesn’t have Facebook (YET) as I imagine it would be terribly difficult for her to relive it. I had the advantage, as I was ready, but it was still awfully sad. But, that time, I didn’t feel as something had been snatched from me; I felt  something was given to me-Hope. Even as I watched her new found skills go away one by one, each loss was a gain to my heart.

What can be said to someone who wasn’t there? Would they believe the sweat on my daughter’s hands if they hadn’t felt it, smelled it’s musky scent, seen with their own eyes the incredulousness in the researcher’s face, mimicked by my own? Or when I saw it soak her back when she was swinging and her face didn’t get red and she didn’t overheat, when their own child cannot even swing?

But, watching and reading has reinforced the optimism and hope that I have carried all these years. Many people don’t know this (well, now they do), but I am an atheist, a weird one I say because I wish people Merry Christmas and Happy Hanukkah, I play Christmas music (Katie loves it and it’s beautiful), I have welcomed prayers and blessings for Katelin and myself from believers of several different religions, well because well wishes are welcome in whatever form and language they come. I am not blind to the goodness and comfort that it brings and people deserve goodness and comfort in their lives, and it is not my place to question their beliefs, only my own. But, I have never understood Faith, believing in something so strongly that you are sure without actually knowing for certain, but knowing for certain anyways. And now, I do. I have faith in Trofinetide, in the science behind it. I know without a shadow of doubt in my mind that my daughter is going to speak, and what’s more, she knows it. (which is why I’m willing to pay for her new phone and minutes in advance). See, I told you I was feeling retrospective.

And, as always, my anticipation and Hope are tempered by the children we- the Rett, FoxG1, CDKL 5 and MecP2 duplication community- have lost in the last year. To those families who spent their first holiday season without their sons and daughters and to those who have spent more than one, you are all in my heart.

So, as we move forward to 2018, a year that will find us journeying into the great unknown, a final frontier of sorts, I am reminded of a question posed to Neil deGrasse Tyson-What is the most astounding fact you can share with us about the Universe. In essence the answer is… we are made of stardust. I think that is why Man always strives to question, to seek, to reach for what seems unattainable and we make wishes when we look up to from whence we came. And in a way, when we make a wish, say… that the doctors and researches find a way to help our children, we have wished on stars. And sometimes, if it’s a very big wish, made by many, many people it comes true. I have faith.



Posted in boys with Rett syndrome, Communication, cure, FDA, hope, MecP2 duplication, Neuren Pharmaceuticals, NNZ-2566 trial, Rett Research, Rett Syndrome,, Talking, Texas Children's Hospital, Trail to a Texas Trial, Trofinetide, Trofinetide Pediatric trial, Trofinetide Phase III | Tagged , , , , , , , , , , | 2 Comments

Thank you, Neuren

Dear Neuren researchers, administrative personnel and stock holders and everyone involved in the journey we’ve been on for four+ years now. This post is just for you. Today, my Christmas present was watching Katelin’s joy at holding her very own phone and getting to enter her phone number in my contact list. This moment, like many other wondrous moments, was brought to my girl by you. Merry Christmas, Happy Hanukkah, Happy Holidays. Wherever this day finds you may it be as filled with joy as ours.


Posted in Neuren Pharmaceuticals, Uncategorized | Tagged | Leave a comment

Christmas Wonderland

Every year for the past 18 years I’ve asked Santa for a cure for Rett syndrome. (Katie was 6 when the gene testing became available and we knew with absolute certainty she had Rett syndrome). Every year except this year. This year we had different wishes. My wish was for Trofinetide. But, it’s what Katelin wants most that we asked for.

She wants a phone. She’s wanted a phone since the Phase II adult trial results came out. And, today, I am SO CONFIDENT in what Trofinetide will do for her that today we asked Santa for a phone, an orange one. In fact, I am so confident that the elves knew in advance and asked her if that’s what she wanted and when she smiled, they went ahead and let her know that Santa was absolutely going to give her her own phone. And, then…Katie clapped her hands.

Do you know what THAT means? That means KATIE is so confident of what Trofinetide will do, that she KNOWS a phone is exactly the right present for her.

And so the one thing I’d been absolutely certain for 20 years that Santa would never bring her is the top thing on her list. HER list. Not mine, not what I think she wants, but what I KNOW, without a doubt, she wants. And truth be known that is the biggest vote of confidence Trofinetide can get, imo. A child with Rett syndrome clapped her hands when told Trofinetide is coming and she can have her phone.

Merry Christmas to everyone, but sent with an extra warm hug to all the researchers and stock holders that have a heartfelt interest in my girl.

Posted in Communication, hope, Neuren Pharmaceuticals, Rett Research, Rett Syndrome, Talking, Trail to a Texas Trial, Uncategorized | Tagged , , , , , , | 1 Comment

What do Halloween and Rett syndrome have in Common? Superheroes.

hero-2604966_960_720Today is the last day of October. Another year gone by from one Awareness Month to the next and still no treatment. But this is not a humdrum post BECAUSE treatment is now within sight. Each year in October superhero parents put on their capes and causes and go out into the world and educate, fund-raise, sell raffle tickets galore. These parents astound me. Every time I see a gala, golf tournament, comedy show etc. I’m simply flabbergasted at the effort, truly awed. I’m not one of them. I write and hope somewhere, somehow it reaches people and moves them to research Rett syndrome and maybe donate, because the donations are working!

There is an incredible amount of research going on in this field and multiple studies either in the works, recruiting, on-going or just completed. THIS is what Rett parents and caregivers need to be aware of- the research is happening, donations are coming in… but without people signing their children up for clinical trials none of it will matter.

Newron (not to be confused with Neuren) is conducting the Sarazotan trial for children with breathing difficulties. They are having a great deal of difficulty filling the necessary spots. Click HERE to see where active trial sites are or for more information from the site-Click HERE and the RettSTARS website. This is one of the few trials that is occurring in countries other than just the United States-Australia, United Kingdom, Italy, India

One of the most anticipated trials coming up is the Phase III pivotal trial of Trofinetide, to be conducted by Neuren. This trial will begin recruiting in the next few months, and in my opinion represents the best chance right now for addressing the symptoms of Rett syndrome and has been shown to have the possibility of modifying the course of the disorder. Anyone can go to to review all their announcements and trial results.

Anavex has developed a compound Anavex 2-73 which has been shown to be tolerated in human studies. They are beginning to reach out with a preliminary questionnaire for interested parents, which you can access- HERE There is a short information video as well.

The Natural History Study is an ongoing, years long, collection of data. Parents are encouraged to enroll their children in this study, not only is it imperative to collect data in the long term, but it is possible that future trial participants will be taken from those enrolled, as this will have the most up to date data on each participant, in addition to a well documented progression of the disorder.

A quick search on shows 42 trials in some phase of completion, ranging from “not yet recruiting” to “completed” or “terminated”. I hate that one, “terminated”, meaning for some reason or other it was stopped prior to actual completion. But the exciting thing is the number of trials-42! and on such a rare disorder, too.

So, this is a time to be hopeful and to be aware that there are people out there, hidden behind masks and scrubs, that are doing their damnedest to help our children. I know when parents/caregivers see another trial come to an end and still nothing is approved it is a rollercoaster of emotion, we get weary of hoping at times; sometimes we are cynical; sometimes we just can’t bother to even care- who can blame us when we know so many children for whom a treatment/cure will never come. But then, I look at Katie who was so brave during her trial, my superhero, and I know if she can be that brave, so can I; I know that our community is chock full of superheroes in every shape, size and gender. We are formidable and we will win in the end.




Posted in Anavex, Anavex 2-73, boys with Rett syndrome, cure, fund-raising for rett syndrome, Neuren Pharmaceuticals, Newron, Rett Research, Rett Syndrome, Rett syndrome Awareness, sarizotan, Trofinetide, Trofinetide Phase III, Uncategorized | Tagged , , , , , , , , , , , , | Leave a comment