Clinical Trial of some FDA Approved SSRI's for treatment of seizures in Dup15q Syndrome and serotonin/dopamine supplements

An unbiased drug screen for seizure suppressors in Dup15q syndrome reveals 5HT1A and dopamine pathway activation as potential therapies - PMC (nih.gov)

How fascinating and clever is this research study done to find already FDA approved drugs to treat seizures in Dup15q Syndrome!!! This bypasses drug discovery starting from scratch which can take decades to create the drug, do clinical trials and then get FDA approval, time my son can't afford to loose.  This group must have felt the urgency of parents to find seizure treatment and bypassed all that work and went straight to a databank of already FDA approved drugs and engineered drosophila flies that mimic Dup15q Syndrome and screened them for seizure reduction against a variety of drugs.  It turns out that drugs that showed most promising belong to a class of antidepressants notably Mirtazapine (trade name, Remeron).  In jist, these drugs modulate serotonin levels in the brain much like SSRI's. The mechanism of action is by stimulation of serotonin receptor 5-HT1A while inhibiting another receptor 5-HT2.  They showed that if 5-HT1A is inhibited and receptor 5-HT2 activated, the seizures get worse.  The results showed over 55% reduction in seizures with Remeron followed closely by Lyrica and wellbutrin.  The principal investigator stated in an interview that a new antidepresant drug trintellix/Brintellix may have more specificity to a target site than Remeron!  That is exciting and promising news!  About 10 years ago, I suggested to a parent support group that given the symptoms so many with the syndrome experience such as anxiety and GI issue that serotonin levels were low and maybe SSRi's could help with the syndrome, although I wasn't thinking of seizure control at the time. I considered adding 5HTP or other serotonin supplements to Luki's diet but gave up pursuing the idea because he was so young at the time and I was already experimenting with DHA, accupuncture, CBD oils, creatine, CoQ, etc... I wonder now how his seizures would have been controlled had I started him on the supplements.  It is really hard when there is no one else giving it to their children and all I am going off is my hunches and intuition with no confirmed scientific data.  I had to wait 10 years for that! I need to listen to my intuition more often! The thing is, when I first got the diagnosis, I was in fight or flight mode and we've heard of people who obtain supernatural abilities and strength in dangerous predicaments.  There have been stories of mothers able to lift heavy trucks to save their babies in danger.  I think in the beginning when I was in the flight or fight mode, I had so many ideas come to me (not so much now, I've grown accustomed to the condition) most of which I had no ability to pursue.  Had I gone to our neurologist 10 years ago and requested SSRI or Remeron for Lucas, they would have labeled me as "that crazy mom" and shrugged me off.  I also remember a lively discussion with another mom linking sodium channel modulators in the brain of Dup15 to control seizures.  I never followed up with it but now I wonder if there is something do it.  Maybe I need to wait another 10 years for research to make the connection...

It’s so ironic that such widely used medications right under our noses may be potential treatments! I’ve always felt shooting random AED’s without actually understanding the underlying pathology is missing the mark and may do more harm than good - or at most only serve as a band-aid for a bigger problem. We need a med that works like a key to open a lock, something specific to this disorder rather than using a hammer to break open the lock which is why I prefer to live with the few seizures he has at night than add another AED or two. I worry these meds will irretrievably remodel his brain chemistry over time and do more harm in the long run. I wish clinical trials for trintellix can happen soon. I hate seeing so many drug commercials on tv but Trintellix is so familiar to me from the ads.  The study suggests Trillentix/Brillentix may be more specific than Remeron. If Remeron reduces seizures by 50%, I wonder what the percentage reduction will be with trillentix!

For 3 nights, we have had Luki on dopamine/serotonin supplements. I haven't started the 5 HTP, yet as I am trying one at a time.  The last two nights, his seizures have not reduced in frequency, but they seem to be milder.  While on most nights he thrashes about in bed with arms flapping and legs kicking; after the supplements, he no longer kicks his legs. On his first seizure at 1 am, he just jolted up and stared off as if in surprise.  Usually, he will thrash about.  This morning he had another one and we noticed that he did not kick his legs but just flapped his arms.  Coincidence?  We will wait and see.  The dopamine/serotonin supplement needs to be taken for 5 days then off for two days. I am a bit concerned that the data shows only 33.3% seizure reduction with serotonin itself versus over 55% reduction with Remeron. And how the heck does an eye drop dorzolamide reduce seizures by 50%? And meclizine, an anti-nausea medication reduces seizures by 43.8%??   Although Felbamate (50% reduction), works well for some individuals with Dup15, we have not had much luck with it. The results kind of seem to be everywhere and nowhere.  

I only give Luki half the recommended dose of the serotonin/ dopamine supplement and only at nighttime.  I break open the capsule and mix it with his yogurt. I will also present the data to his neurologist to see if he will be agreeable to prescribing Remeron.  Although, prescription medications have their side effects, too one being increased thoughts of suicidal ideations.  It baffles me how an antidepressant actually makes you want to kill yourself???  Also, starting and stopping SSRI's need to be done judiciously and titrated carefully.  If the supplements do their magic, maybe I don't need to get prescription drugs.  Let's wait and see what happens.  

*******

Day 4 update:

On day 3 I reduced his night time dose of lamictal to half and skipped his morning dose.  Bad idea.  He woke up crying for about 5 minutes.  It seemed like he was having pain (headache?).  He also had one of his usual "wake up" seizures.  Maybe taking away the lamictal was too soon? I will give him his morning dose and only half his night time dose and see what happens.  I am keeping him home today to monitor more closely.  So far so good.  He is back to his cheerful self and ate a very good breakfast.  

Day 5 update:  No morning seizures noted.

Day 6 update:  AM seizure with flapping and kicking. 

Day 7 update:  day 1 of 2 OFF day of supplement.  Wake up seizure noted.

Day 8 update: Day 2 of 2 OFF day of supplement.  Wake up seizure noted. 

Day 9 update:  Took supplement at night.  No morning seizure on day 10.  Giggling noted around 2 am. 

2022

As I bid farewell to 2022, I say adieu with some bittersweetness but also with some relief.  It has been an amazing year of travel adventure for the family as we stayed at a oceanfront airBNB at Oceanside for Gabriel's birthday and went on an amazing cruise to Alaska.  It has also been a busy year for Liam as he has graduated from mommy homeschool Abeka curriculum and started kindergarten at Heights Christian Elementary school.  He has also had quite a busy year of extracurricular activities since the pandemic lockdown has lifted.  He finished a dance class, went to summer camp at Heights, went to Lego Camp for a few days in the summer, swam throughout the whole summer and is now in level 2 and hopefully he can continue on this summer.  Through church, he participated in basketball clinic, golf class and soccer.  He even took 6 weeks of yoga for children through the community center.  He also is finishing up his beginner's piano class and had his first recital at a hall in Mt. Sac College. Liam enrolled in cooking classes as well as Chess master through his school and we made tons and tons of Christmas cookies for the holiday.   Lucas went kayaking and paddle boarding for the first time and did great!  He has always loved water. For Halloween, Liam went as an angel and Lucas as Spiderman.  Lucas is on this last year of elementary school before starting junior high next year.  We are lucky he found a really great 6th grade teacher who is working with him and showing me things I didn't think he could do but is mastering in the classroom such as matching letters and numbers!  His seizures are still at bay with 1-2 occurring almost every morning as he wakes up. 

 Liam had his first school Christmas concert where he fell so hard as he tried to get down the steps that the whole audience gasped with concern.  Luckily, he was not injured and said his line "An angel appeared to Joseph" like a pro. He dressed as a cowboy for a school cowboy themed day and I am sure everyone thought he was just adorable, I know I did.  We spent Christmas with Gabe's parents and visited the Cathedral of our Lady in downtown for mass and surprisingly bumped into the priest who married Gabe and I.  We learnt that he has been promoted to Monsignor and is serving at the cathedral.  Seeing him was such a beautiful coincidence and it was the best Christmas present Spirit could have given me.  For dinner, we did something unconventional and had dinner at Spire76, the top of one of the tallest builings in downtown Los Angeles.  The lights illuminating the city was more beautiful than Christmas light shows we've paid to see and found it awe inspiring to see the city change so much (for the better) over the 42 years since I've been here.  We then visited The Bloc where they had some beautiful lights and show for free and took some memorable family Christmas pictures! After Christmas, the family went to Las Vegas and stayed at Paris hotel for some good food and relaxation.  We had an extravagant dinner at Gordon Ramsay's steakhouse and visited Bellagio to view their beautiful Christmas decorations in the atrium.  In the new year, the family had dduk-guk and went for a walk at the Sequoia forest at Carbon Canyon Park then went to Mt. Baldy for the kids to play in the snow.  New Year in 2023, we spent a quiet day with Gabe's parents and I took all the ingredients for dduk guk and made it at their house.   Liam bowed "sebae" and received money from his grandparents, a tradition I am trying to teach him every year. 

Overall, it's been a great and memorable year.  The only downside has been the mess in the cryptocurrency world where my investments totally tanked compared to the previous year.  There has been scandals and the collapse of reputable (or so we thought) centralized exchanges such as FTX and Celsius and I've lost money with the collapse of a certain stablecoin. Although not directedly tied to FTX, some of my investments are locked for withdrawal through its contagion.  But, I am still hopeful there will be an upturn eventually but not necessarily in 2023.  I have hope and conviction that cryptocurrency is good for mankind and that it will help humanity to be on a level playing field to get ahead.  

 

Ahn Family Adventure Series: Alaska, The Last Frontier! Royal Caribbean Cruise Aug 15-22, 2022

 

 Alaska, The Last Frontier!! 

Glaciers, salmon streams, crab feasts, s’mores, bald eagles, bears, waterfalls, Salmon bakes, panning for gold, Tongass National rainforest, picking Black- blue- rasp- and huckleberries on hikes, totem poles, native dances, whale sightings, Pike’s Market, Space Needle, and Timbits at Tim Horton’s!! It’s been so much fun!  Seattle-Snoquolmie Falls-Ketichan-Sitka-Juneau-Mendenhall Glacier-Victoria, Canada 

If you're a mom, a family vacation is never really a vacation.  You are still working as a team leader, a coordinator of events/meals, the enforcer of the itinerary and thinking of a thousand plans, back up plans and back up for the back up plans and making lists of what to do just in case. It can be exhausting and sure, it would have been easier to just take the family to the beach or somewhere local for summer vacation but when did I ever do things easy?  Besides, I needed to check off a few things on my bucket list and adventures need to be taken while you're still able bodied because I've seen a lot of older retired folks on the cruise who were too frail for excursions and took head-tilted-back, wide-opened-mouth naps at the pubs.  That may be me one day, but not today. 

Traveling with Luki was relatively easy and we even did most of our excursions without his special needs stroller.  I've recently learned about a program called Autism on the Seas which provide respite care and diverse activities for individuals sailing with autism on select cruises.  We didn't find any such services on our sailing and decided not to leave him at the Ocean Adventures childcare for his age group because they just didn't have a 1:1 staff to be with him.  This wasn't a big deal to me because I loved having Luki around us all the time and found joy in seeing his wide-eyed wonder at everything he saw. 

Luki. This kid is amazing! Despite his disability he did Alaska like a pro! He may never go to the best school but he still gets to see and experience the world and learn. He kept up beautifully with the rest of us during hikes, shows, meals and bus/boat excursions. He was so quiet and so in tuned with the surroundings and it was wonderful to watch him like that. He even joined in on the native dance show during our excursion to Sitka (see video below for Sitka).

I am so grateful to fellow travelers who showed much compassion and understanding to him. To the lady sitting in front of him in flight who wasn’t bothered by his occasional screams, kicking her seat and said he did well at the end of the flight, thank you. To the couple sitting next to us at the restaurant who didn’t mind his occasional outbursts (he was just excited) and even offered to take our family picture for us and said my kids are a joy, thank you. This is the power of what disability awareness can do. I am so proud and grateful to all of them!! Another mom with a Dup15q child said when her son kicked the seat on an airplane, the women seated in front turned around and tried to hit her child. This teaches me to never take any pinch of kindness for granted.

People like Luki are not meant to be kept aloof from society. They need to be seen at the mall, the grocery store, parks, sporting events, schools, and even while traveling. They may get hated, they may get loved, but they need to take part in the world. And as his parent, I also get to bear witness, in front row seats, if you will, to the highest virtues of humanity as well as the basest.

Tae makes sure Luki is looking into the camera for photos

I give Best Little Brother Award to Tae for his awesome care of Luki during his Alaska trip. From reading about Alaska to Luki, to making sure he is looking at the camera when taking pictures, to taking responsibility of pushing the stroller (by his own volition), helping to feed him during meals and being a great companion. He always looks for Luki when he is not around and Luki’s face lights up when Tae is nearby. Tae sees his older brother like a warm security blanket. I thought Luki will need his little brother more but I’m realizing Tae needs him just as much. The special bond I see blossoming brings me to tears.

Tae keeps Luki from eloping during photos

Luki loves his little bro

Tae says, "I've got this!"

A Brother's Keeper

 

Tae loves to get shaved ice after his summer day camp lets out at mid-afternoon and I indulge him once a week at either Hawaii Time or Snowy Village which makes amazing Korean shaved ice specialties.  Lucas is still on his summer vacation and after playing in the pool and backyard all morning, I took him to pick up Tae and to enjoy a treat at Snowy Village.  With Lucas trying to escape my grip and toppling over the tip jar as I pay for our treat, I finally manage to get him seated in his adaptive chair.  He gets very fidgety in his seat and although secured in a belted adaptive chair, he will rock the chair which makes a noise when the chair leg hits the floor.  I noticed a Korean women with her young daughter about the same age as Lucas seated two tables away and felt a weird vibe coming from them.  My back was turned towards her so I could not tell if she was staring at Lucas but I sensed her annoyance whenever the chair made a noise.  She spoke in Korean to her daughter saying, "how noisy" or translated in another way, "what a ruckus".  Honestly, it wasn't that loud.  I wanted to lash out and ask what the hell is so loud but decided not to cause a scene.  I wonder how Korean society views people with intellectual disability and what our lives would have been like if we lived there.  Would the restaurant owners ask us to leave for being loud?  Would there be sympathy for us or for the annoyed lady.  Do they even have a law for disability rights protection as we do in the States?  

I am currently watching a gem of a Korean drama called Our Blues.  I cried and laughed at almost every episode and found it to be so authentic in depicting Korean people's spirit so well. I once heard that it's difficult to distinguish whether two Koreans yelling at each other are actually arguing or are the best of friends.    I would characterize Koreans as generally being very blunt to the point of being offensive, but without guile and although they don't show affection outwardly, they have deep love for each other.  They can be loud, loves singing, dancing and drinking, full of "han" and have quick brilliant minds and can be very not politically correct.  There is a saying that a Korean mother shows her love not by saying I love you but by asking, "Have you eaten? or by shoving a wrapped ssam in your mouth.  This series reminded me of all the extended family members I interacted with until the age of 7 when we immigrated to the US.    

In one episode, a poignant scene depicts the dilemma of a sibling to a twin sister with Downs Syndrome and the struggles she faces as she takes on the responsibility of being the sole guardian to her disabled sister after both her parents tragically pass away from a car accident
.  She worries her boyfriend would be put off by such a responsibility and explains to him the challenges she has faced in the past and how difficult it has been to be her sister's caretaker

   Watch here. 

I wonder what our lives would have been like if we lived in Korea with Lucas disability....  One thing that struck out in this scene is when she puts blame and responsibility on families who send their disabled children away to secluded group homes, away from interacting in public life as the main reason why people stare at disabled individuals like those with Down Syndrome.  It seems natural, if you have not had exposure to something, curiosity naturally makes people stare and gawk.  Her solution is to have more inclusion and exposure of people with disabilities in the community so that their presence no longer feels like an oddity.  Her complaint is that there are not enough resources and support for families to take care of them in their own homes when they must leave to work and make a living.  

I know many parents that have kids with intellectual disabilities share ideas of a group home or communes in the desert or even a farm far away where the kids can live out their days in remote settings.  Isn't there a saying in English about sending grandma off to the farm and it being connotated as having her die or be killed?  I dislike this idea because it defeats the whole purpose of why these precious souls are here on Earth in the first place.  They are here to make people feel uncomfortable with their presence.  They need to be seen in the communities where they live.  They will get stared at and ridiculed but their mere presence is their divine ministry.  Unlike a preacher with many words, their mere presence delivers the whole sermon.  

Here is documentary based in Denmark of a sister to a child who is deaf, blind and has autism.  She also grapples with the issue of who will take care of her brother once her parents pass away.  

He's My Brother | POV | NJ PBS (njtvonline.org)

Tae was not conceived to be his brother's caretaker when Gabe and I are no longer here on Earth.  I want Tae to pursue his own dreams and ambitions in life and fly freely and loftily without having his ankle chained to the burden of caring for Lucas.  It would be amazing if he stayed close and chose to be his guardian but I will not burden him with it.  It makes me sad to think that he would not choose to be a part of Lucas life but it would crush me even more to think that he forfeited his dreams to spend the rest of his days changing Lucas diapers and feeding him.  

Give Big Live Event Interview

The above is an interview of me with the executive director of the Dup15q Alliance on the 5th Big Give Fundraising event to raise funds for the LADDER  (Linking Angelman and Dup15q Data for Expanded Research ) project, which is a stored database of Dup15q individuals that helps scientists and pharmaceutical companies access information for drug development and research.  The greater the depth of information stored in the LADDER database, the easier it is for potential researchers to tap into and become interested in pursuing Dup15q Syndrome as a research project or a marketable candidate for drug development.  

We need answers.  I remember the excitement I had when I got an answer for one of Lucas behaviors.  There was a Japanese research group who were successful with carrying out behavior experiments with Dup15q transgenic mice and in one setting, the mice were placed in a maze and their behaviors recorded.  The mice did not roam around the maze to look for food or stimulation but rather stayed clustered to one corner of the maze.  The researchers concluded that the mice hesitated to explore due to high anxiety.  Lucas behaves exactly like these transgenic mice when placed in a large indoor playground, I'd pay an admission fee for him to explore the whole area with swings, slides, jumpers but he would only stay within a mere 8'x8' area and seem perfectly content to just walk within its perimeter.  I always wondered why he never explored further but the research paper concludes it is due to high anxiety.  I would agree that the anxiety comes from not being able to decipher his environment properly.  In fact, I would also add to the scientists conclusion that poor vision or a poor visual processing ability adds to the anxiety.  If I were blind or see the world as a jumbled kaleidoscope of colors and shapes, I'd be hesitant to walk around myself.  

I am realizing, as I alluded to in my interview, that the knowledge and treatment strategies Lucas and our family get privy to is all thanks to the work that was done before we even arrived on the Dup15q scene by families that never gave up and pursued answers to some of the mysteries surrounding the syndrome.  What families do today will help people that join in the future perhaps even more so than us right now.  I am so grateful and feel fortunate that one, we have a diagnosis.  There are many people in the rare disease community who don't even have that!  It can be a very frustrating and scary place to be in the unknown.  I remember a 34 year old intellectually disabled lady at church who still does not have a diagnosis even after genetic screenings.  Secondly, I am grateful for the Alliance.  The Give Big Fundraiser prefaced their event with the quote that this syndrome doesn't come with a manual but only with a family that never gives up.  But for me, the Alliance has been my manual with answers to any questions I have be it seizures, therapies, drugs, special needs laws. etc... It is a go-to first line of reference I use for any questions I have and if I want to explore a topic further, I venture into the University of Google to take a deeper dive into it. 

There are so many questions yet to be answered.  Why do some individuals suffer severe seizures and other not?  Why do some experience severe behavior and anxiety issues while others don't?  Aside from the same duplicated region of the chromosome, do epigenetic factors play a more crucial role in determining the severity of symptoms?  The urgency of deeper research can't be minimized because individuals and families are suffering and some are even dying.  

I am reminded of the Pulitzer Price winning author, Pearl S. Buck's daughter who suffered intellectual disability due to a metabolic condition called PKU.  She had a genetic condition which disabled the metabolism of one amino acid, phenylalaine, leading  her to live her days in a care home for the rest of her life.  Pearl S. Buck once admitted in an interview that the motive for writing The Good Earth was so that she could insure funds for the care of her intellectually disabled daughter after her own passing.  She accomlished that and so much more by becoming a world renowned author and ensuring her daughter was well taken care of (into her seventies!) in a group home.  After her daughter's death, scientists discovered that by eliminating one amino acid from the diet, the syndrome was cured.  Today, the condition is 100% curable by diet modification.  How wonderful would it be if Dup15q Syndrome was so easily cured!  Who knows?  It may be cured by adding one supplement or eliminating one metabolic factor!  These are among many hypothesis and experiments that need to be explored.  With this in mind, the Lucas T. Ahn Family Scholarship aims to inspire budding young scientists to get a taste of a research milieu in hopes they will consider working to better elucidate Dup15q Syndrome as their profession.  Who knows?  Maybe they will be the future scientific advisory board members for the Alliance.  Currently, there is a handful of advisors but imagine what 50, 60 or even 100 scientific advisory board members would look like!  100 researchers all working to solve the riddle of Dup15q Syndrome!   That would be super exciting! 

JiYoung on Sesame Street

If you asked me when I was 7 years old that one day there will be a Sesame Street character by the name of JiYoung, I would have responded, "when dockeys fly!"  Here we are at 2022 with a Sesame Street character by the name of JiYoung!

whoopi Goldberg      https://fb.watch/cVF3b2ITEY/

 

Spring Break 2022 & Vist with Uncle Mik