July 2024 Newsletter: Treatments and Trivia
Mitchell-kid Michael displays fruit flies that have been genetically altered, in the research lab of Dr. Hyunglok Chung at Houston Methodist Hospital.
Dear Friends…
Part of the work of The Mitchell and Friends Foundation is connecting people and families together. With only 31 known cases of Mitchell Syndrome in the world, it’s important that we stay tethered for encouragement and support. To that end, we are thrilled by the friendships and relational networks that have formed in our small but growing community, which now extends across a dozen nations.
But really, what we most want are treatments and cures. With your financial support and the generosity of researchers and scientists, that work is proceeding—in many ways, and at multiple locations. Given the paramount importance of this work, we thought a brief update on three possible treatments for Mitchell Syndrome would be appropriate in this month’s newsletter.
RIBOFLAVIN RESEARCH AT HOUSTON METHODIST HOSPITAL
Multiple patients with neurological symptoms—symptoms that turned out later to result from Mitchell Syndrome—were originally thought by doctors to have a Riboflavin deficiency. Riboflavin, or B2, is a vitamin we use every day but one which our bodies have limited space to store. A deficiency in Riboflavin can cause many of the symptoms seen in Mitchell Syndrome patients—skin and eye problems, especially. Thinking these patients perhaps had a simple B2 deficiency, doctors prescribed supplements. While these patients went on to receive a formal diagnosis of Acox1 gain-of-function (Mitchell Syndrome), the patients also reported, anecdotally, that the additional Riboflavin seemed to help.
Dr. Hyunglok Chung—one of the discoverers of Mitchell Syndrome in 2017, and a Scientific Advisor with the Foundation—is currently investigating, in a clinical setting, the effect of B2 on fruit flies that have been genetically altered to have Mitchell Syndrome. If Riboflavin is effective on Mitchell Syndrome patients, Dr. Chung wants to know why, and how, so that more formal clinical trials can be set up.
In the meantime, since Riboflavin is harmless and readily available at any drug store, most Mitchell Syndrome patients are currently taking oral doses. Some even report seeing a slowdown of symptoms. We don’t necessarily know why it’s helping, and how much it is, but sometimes that’s how medical advancements are made.
ASO RESEARCH AT WASHINGTON UNIVERSITY
Researchers at The Miller Lab at Washington University are moving forward on a different line of investigation. Antisense oligonucleotides (ASOs) are synthetically created chemicals that can bind to a person’s genetic material, in order to counteract genetic mutations. Since Mitchell Syndrome results from a mutation on the ACOX1 gene that leads to the overproduction of hydrogen peroxide (H2O2) in certain types of nerve cells, a successfully-engineered ASO can, in theory, modify the expression of that gene so that it does what it’s supposed to.
ASOs are cutting edge research, and highly experimental. There are many steps yet to go in determining if ASOs can be successfully used to treat Mitchell Syndrome. The staff at The Miller Lab are using cells from biopsies of Patient #1, Mitchell Herndon, and other Mitchell Syndrome children to create experimental cell lines that can be used in ASO research. If the experiments prove successful, treatments will have to be administered through lumbar punctures to get the ASO as close to the nerve cells as possible. The treatments will also be very expensive, and there is no guarantee that insurance companies will pay for them.
All that to say, while ASO research is promising, there are many hurdles to jump over. But the fact that we’re even on the track is cause for hope.
NAC, NACA AND THE FDA
One of the earliest considered treatments for Mitchell Syndrome was N-Acetylcysteine, or NAC. It’s an over-the-counter antioxidant that helps clear the body of unhealthy toxins. As mentioned, and as far as we know, Mitchell Syndrome results from a buildup of hydrogen peroxide (H2O2) in nerve cells. While H2O2 is good to have in your medical cabinet for cuts and scrapes, it is very toxic in cells, killing the cells in which it is stored.
An early researcher at the Undiagnosed Disease Network was the first to recommend NAC as a possible over-the-counter treatment for Mitchell Herndon’s ACOX1 gain-of-function disease. Towards the end of his life, Mitchell was taking several doses a day—as are many current patients, who report improvement. However, NAC has difficulties crossing what’s known as the “blood-brain barrier”—a wall of separation between the nervous and circulatory systems. For several years, doctors and patients have been trying to access a version of NAC that has been chemically altered to cross that barrier: N-Acetylcysteine Amide, or NACA. This drug is also experimental and was developed for an unrelated disease. The manufacturer of that drug has made it available for Mitchell Syndrome patients, but given the experimental nature of the treatments, it has yet to be formally approved by the Federal Drug Administration (FDA).
Negotiations with the FDA are ongoing, though. They have requested a plan from Mitchell Syndrome doctors on how the drug will be administered alongside other treatments, and how it will be monitored to measure its impact. Given that many Mitchell Syndrome patients are currently relatively stable—perhaps from Riboflavin treatments or other causes—the FDA wants to be cautious. They’d prefer not to muddy the waters so that we don’t get confused about what kind of treatments work best in the treatment of Mitchell Syndrome.
The fact that we have three promising, possible treatments of Mitchell Syndrome is humbling. We have only known about this disease for a few years, and with only 31 known patients in the world—alive or deceased—we are beyond grateful that so much progress has been made on behalf of such a small population. We know that a clinically proven, government-approved cure is a long way off. But these patients are our children, grandchildren, brothers, sisters, parents, friends, neighbors, and coworkers. They—and the unidentified number of other patients battling this disease—deserve our best efforts. They might not have much time.
But with however much time they do have, they should know that progress is being made. With all the researchers and scientists working hard on the case, we might just yet defeat the rarest of rare diseases.
With hope,
Matt and Michele Herndon
The Mitchell and Friends Foundation
REGISTRATION IS NOW OPEN FOR THE 2024 MITCHELL AND FRIENDS TRIVIA NIGHT (RARE THINGS EDITION) at the Moolah Shrine Center in West County St. Louis, on Saturday, Sep. 7, 2024. In recognition of Mitchell Syndrome, the rarest of rare diseases, the evening will feature eight trivia rounds of "Rare Things": rare objects, rare feats, rare conditions, rare phenomena, rare music, and rare, never-before-seen footage of Mitchell Herndon, Patient #1.
Reserve a table for your team of eight, sponsor a table and/or round, or donate your auction and raffle item. Visit our EVENTBRITE PAGE or go to our WEBPAGE for more information. All proceeds of this event go towards our fundraising goal of $120,000 for support of families with Mitchell Syndrome, and research into possible treatments for this deadly and rare neurological disease.
Want to support the cause but don’t live in town? Sponsor a table or round or donate an item! Want to come but don’t like trivia? Come anyway! I't’ll be a blast, and for a good cause.
Remembering Tyrrell
We were saddened to hear of the recent passing of Tyrrell Nall, a Mitchell Syndrome patient living with his adoptive family in Louisiana. Tyrrell was a 19yo young man with a variety of medical diagnoses and challenges, including Cerebral palsy and Baraitser-Winter syndrome. After genetic testing two years ago, he was also diagnosed with ACOX1 gain-of-function disease (Mitchell Syndrome). While Tyrell was nonverbal and lived his life in a wheelchair, his mother, Gwen, says that he had lots of personality and was very social with his siblings and friends. He had a contagious smile, loved to be tickled and picked on, and especially liked to be carried and cradled by Gwen’s oldest son. He also liked loud music and noises. Given his challenges, doctors weren’t optimistic at how long Tyrrell might live. But he outlived their predictions and even managed to graduate from high school last year! This young man will be greatly missed by his parents, teachers, friends, and many brothers and sisters. (He had three adoptive siblings and five biological siblings.)
We are grateful that increased awareness of Mitchell Syndrome allowed us to connect with Tyrrell and his family, and we hope that as the Foundation grows, we can provide additional support and encouragement to families like his. And we are compelled by the memory of children such as Tyrrell who are no longer with us, but living in our hearts and minds, pushing us forward until we have defeated the rarest of rare diseases.
Catching Up with Cole
While attending the Global Genes Rare Drug Development Symposium in the northeast two weeks ago in her role with the Undiagnosed Diseases Network Foundation, Mitchell and Friends VP Michele Herndon took a very long Uber drive to visit the Canning family in Bristol, Pennsylvania. Cole Canning has been battling Mitchell Syndrome for several years, but is currently doing great with his trach, disability accommodations, and medical treatments. He has wonderful parents, a fantastic support community, and a VERY helpful big sister. On the night of Michele’s visit, Cole's family had just returned from their final session for ASL (American Sign Language). One of the symptoms of Mitchell Syndrome is deafness, but Michele says is was "so cool" seeing this family communicate with their hands and expressions. We've met the Cannings several times over zoom and social media, but were thrilled to finally make the connection in person. We will need to stick together to defeat Mitchell Syndrome, and no Uber drive is too long to visit friends.
