We are very pleased to announce the addition of Dr. Wendy Chung as a scientific advisor to the Foundation. Dr. Chung is a clinical and molecular geneticist and the Chief of the Department of Pediatrics at Boston Children’s Hospital and Harvard Medical School. Dr. Chung directs NIH funded research programs in human genetics and is a national leader in the ethical, legal, and social implications of genomics. She was the recipient of the Rare Impact Award from the National Organization of Rare Disorders, and is a member of the National Academy of Medicine and the American Academy of Physicians. Dr. Chung received her B.A. in biochemistry from Cornell University, her M.D. from Cornell University Medical College, and her Ph.D. from The Rockefeller University in genetics.
Remembering Alice
Alice's mom reached out recently checking in on our progress. Gwen shared her beautiful rock art, this picture is the first she did to commemorate her beautiful daughter Alice. I asked Gwen if she could share her story about Alice, this is what she had to share:
In 2010, my then-wife Lonnie Hardage and I wanted to add to our large family of birth-kids and adopted-kids. Our adoption worker showed us a picture of a brother and sister. ages 6 and 4, who needed a forever family. When we met these dear children they were both developmentally delayed and the little girl had some balance issues that looked to me like cerebral palsy (I am a pediatric OT and SLP). I thought, "We can certainly handle this, and she'll have company, because one of our other kids has CP."
Alice and her brother came home and she blossomed, learning to walk with less falling, starting to talk, feeding herself, and almost being toilet trained. Then suddenly, at age seven, she started losing ground in her abilities. Lonnie took her to a neurologist who hospitalized her for tests; the next day the verdict came: not CP, but rather TUBB4A leukodystrophy, H-ABC. Shattering news, although at that point we could only find record of about 14 other children who had this (the founding families of the H-ABC Facebook group) so it seemed as though there must be things doctors didn't know yet; they couldn't possibly have formed rigid conclusions with such a small sample of children. We did not want our hope to be dashed. Gradually Alice lost skills. She needed a walker and we pulled her out of the first grade class at the Waldorf charter school without ADA-compliant ramps to her classroom. Soon she needed a wheelchair. Her ability to talk was nearly gone, so we tried first a fancy AAC speech-generating device with "robust capabilities for language"-- but it was more than she could understand. We ended up using a paper communication book of PODD (Pragmatic Organization, Dynamic Display), which Alice and I became really good at using together; she could even make up stories with it. Unfortunately, not many other adults came to enjoy using it well, so Alice had limited conversation partners.
Alice had surgery to get a g-tube (which we combined with a reduction of her salivary glands, hoping she would drool less). In hindsight I would not have done that, because the remaining salivary glands seemed to overcompensate, and much drool soon continued. She joined a special day class at the local public school. Through all these changes Alice maintained her joyful attitude toward life and her wish to love and be loved. She was the queen of hugs and loved to be playfully mischievous or involved in a marathon of "hide and seek." She had a crush on the teenage boy across the street. If she cried and I made her laugh about something, she would seem to forget that she had been sad or mad. At first I worried this was not fair for her emotional development, but as she lost ground I decided it wouldn't be detrimental to relieve her discomfort with a tickle or silly face. Lonnie and Alice attended a gathering of families coping with H-ABC in Philadelphia in October, 2014, where she was thrilled to meet other children like her and where she had a consult with Dr. van der Knaap. There was hope, research was beginning, and more and more children with H-ABC were being identified.
Alice loved her social life at school and hated to miss a day. Even when she began to develop intractable body pain she wanted to go to school. Lonnie was on the phone with doctors daily, getting stronger pain medicine that still didn't reduce the aching in her body. On her last week of life she attended school on Monday and Tuesday, stayed home sick Wednesday, and went to the ER on Thursday where they finally gave her a sedative strong enough to let her sleep. She did not wake up from this sleep. Alice died Friday, August 30, 2019 at age 13. My belief is that her body wore out from fighting the pain.
Rest in peace, Angel Alice. And may the search for treatment for H-ABC continue until an accessible, affordable, internationally available cure is found!
Updates on Preclinical Trial Readiness
Below is a summary from Children's Hospital of Philadelphia (CHOP) on their work in preparation for the ASO clinical trail. CHOP is working alongside SynaptixBio.
Impact of Disease: This work includes interviews and surveys conducted with families, focusing on the impact of TUBB4A on children and their families. Parents provided feedback on the topic and expressed priorities for factors that could potentially improve overall quality of life. The project has ended, and a manuscript is currently under revision. Once available, I will be happy to share the link to the manuscript for easier access.
The Natural History of Variable Subtypes in Pediatric-Onset TUBB4A-Related Leukodystrophy: We are concluding a project involving more than 200 children with TUBB4A-related leukodystrophies (both U.S.-based and international). In this work, we explore medical events occurring in this population and aim to identify early predictors of disease progression. The manuscript is currently being prepared and will be submitted for peer review soon. Once accepted and published, we will share the link to the manuscript as well.
**** Clinical Trial Readiness in TUBB4A-Related Leukodystrophy:**** In alignment with recent FDA guidelines on Patient-Focused Drug Development (PFDD) (https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical), we are working on creating the infrastructure and developing a methodology to comply with this process.
Retrospective and Prospective Natural History Studies in TUBB4A-Related Leukodystrophy: We continue our efforts to understand the natural trajectories of TUBB4A-related leukodystrophies by enrolling children in our research protocol. Interested participants can consent to our research protocol and share information about their children, as well as participate in our prospective study through assessments focused on capturing gross and fine motor functions, cognitive abilities, and adaptive behavior. This is a fundamental step in identifying potential clinical trial endpoints.
Mira's Story
Mira is 5 years and has been the light in Chloe's life ever since. Mira loves Fuggler teddys and watching cartoons on her IPad. Mira first started showing signs when she was 3 months old and with much investigation and through genetic Testing mom and dad got the diagnosis in May 2022 and it flipped their whole world upside down. There wasn't much if any information until they found the Foundation to Fight H-ABC who been helping them understand what to expect in future. It was hard at first especially when they discovered there is no current cure but Mira hasn't let anything stop her smile!
Mira is constantly fighting and gives us all hope and our biggest hope is that in the future there is a cure!
How Microtubules work and what causes the disruption in the Tubb4a gene causing H-abc/Tubb4A related leukodystrophy
The video is available at https://youtu.be/MZ47-G4XKDw. You can see microtubules being assembled from 1:06-1:10, then disassembled from 1:11-1:15. The next sequence (1:15-1:26) is of a kinesin protein "walking" along a microtubule filament while pulling a vesicle.
Here is a longer (and narrated!) version of this video available at https://youtu.be/FzcTgrxMzZk. Its long but may provide some useful scientific context.
The "vesicle pulling" clip represents intracellular transport. The microtubules basically serve as "molecular highways" for molecular motors that haul protein cargo to different parts of the cell. Variants in TUBB4A gene result in misfolded tubulin proteins, which interfere with the ability of those microtubules to assemble properly - the process in the video - or prevent those molecular motors from attaching correctly, leading to disruptions in those intercellular transport mechanisms.
Promising Pathway Act
The Foundation is very pleased to be supporting this very important act. Why is this relevant to H-ABC/Tubb4A? Clinical trials undergo multiple phases, the first of which is safety, then evidence that specified endpoints or biomarkers are met. Trials often stall due to the difficulty in meeting these FDA requirements. This Act will allow access to a drug if it was proven as safe, but didnt get to commercialization due to the rigid FDA requirements.
https://www.youtube.com/watch?v=HgcRCKdf9qg
One Pager on the bill - https://www.braun.senate.gov/wp-content/uploads/2024/05/PPA-2.0-One-Pager.pdf
Peace of Woodstock Fundraiser
Tuesday, February 12, 2024 | The Savannah Center, The Villages, Florida. More details to follow!
A Year in Review
A year of contemplation, preparation and patience for the Foundation
Along with our sister foundations in the UK and Spain we have expanded our outreach to families helping them connect with physicians, resources and other families living with h-abc. This is an important part of our work to connect families from across the globe desperately trying to help their children as this is still an unrecognized disease which still even the physicians don’t know how to treat.
We, along with the UK foundation continue to advance efforts to find a cure using ASOs, a treatment that requires ongoing injections to stave off the side effects of the disease. In addition, AAV gene therapy has just entered its third year of research which, if successful, will provide a permanent cure stopping the progression with a one time treatment. Our efforts collectively entail funding the research and the clinical patient natural history studies critical for future trials.
2022 was an important year for us to introduce h-abc to the FDA. During a two hour listening session we presented clinical details on the disease as well as our experience as parents and caregivers and the impact it has on our children. The FDA talks all the time to researchers and pharmaceutical companies, but they want to see and hear from the patients and caregivers too. Our session was a big success and a summary is available to view on the FDA website https://lnkd.in/g_HfEGbi.
This helps anyone across the globe interested in understanding more about h-abc have access to us
This year we also launched our patient registry. The FDA must have patient advocacy representation independent of all the research in order to advance a clinical trial. They want to be able to hear from our patients and be able to connect. We partnered with RAREX and have established a registry that continues to expand. https://lnkd.in/g8nzQGZs
Our 2022 annual fundraiser event entailed a very successful concert in Florida in March with over 1200 attendees. We are planning ahead for our 2023 event in Maryland and we expect it to be one of our best ever!
Looking ahead we are planning a family conference in the Chicago area in late June 2023. The United Leukodystrophy Foundation is hosting a family conference to include researchers so not only our h-abc families can come together but also meet others living with a Leukodystrophy. We will host a half day session on h-abc bringing in key speakers. Family time in these settings is so beneficial for parents and caregivers.
Happy New Year!
FDA Patient Listening Session
On May 9, 2022 several parents met with the FDA to share our experiences living and caring for our children living with H-ABC. Click FDA to link to a summary of this meeting.
Seth's Story
When I received the diagnosis that my son Seth has H-abc Leukodystrophy at the age of four. I was devastated, my whole world came crashing down, a million thoughts raced through my mind on a daily basis. For the next couple of years all I could do was think how could I possibly prepare myself to ever live without my son, how could I prepare myself to watch him deteriorate and eventually lose all function. It is not something that a parent can ever really prepare for. I was so angry at the world and at God for a long time. I have learned to make the best of everyday and make as many memories as possible. Seth is a very brilliant, funny, and handsome little man, full of personality and loves life, he is determined and he is not going to let leukodystrophy stop him. Not long after Seth’s diagnosis, I came across the H-abc parent group and the H-abc foundation and both have given us so much hope. We are not alone, there is so many families that we can relate to. There is so many people that are working tirelessly to raise funds and to find a cure. Thank you to Michele, all of the doners and to everyone that is working towards a cure, It is all of you that is getting us closer to a cure and giving my Seth and all of our beautiful children a fighting chance at life.