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  • Holly Carmichael

1-Year Update


2020 wasn’t the worst year, in fact it’s been one of our best. 2020 was the year dreams are made of when your child has a rare disease. We went from, “there is no available treatment” to improving our daughter’s quality of life through a single-patient investigational new drug compassionate use study. In this picture you see a very proud girl who drew Elsa following her non-artist mom’s step-by-step instructions. Maggie used to only scribble, this is just one example of the many gains she’s made this year.


Quick disclaimer – I’m not a medical physician. I’m mom to Maggie, age 7, PMM2-CDG and co-founder of Maggie’s Cure. Maggie’s Cure was founded by Maggie’s family to help find her a cure or treatment for her condition and funded the research that led to the discovery of this potential treatment. Nothing I write should be taken as medical advice. This is my understanding of the process and our experience.


It’s been a roller coaster of a ride to get to this point from an original misdiagnosis of Spinal Muscular Atrophy to finally learning at 9 months old that Maggie’s condition is called Congenital Disorder of Glycosylation Type 1a, or PMM2-CDG. We scoured the internet in search of answers, in search of any potential treatments or a cure and came up empty handed. We learned that the disease can have a mortality rate of 20%, especially in the early years of life and were terrified after losing our first daughter, Rosemary Beatrice, at just 6 ½ weeks old.


While there was short supply of any treatments or a cure, the CDG community is full of hope, love, courage, and support. We were welcomed with open arms and introduced by Matt Might to cure sherpa Ethan Perlstein and his company, Perlara. Through Perlara’s work, we discovered a potential treatment: an aldose reductase inhibitor called epalrestat.


Epalrestat is a drug approved in Japan in the early 90s for the treatment of peripheral neuropathy in patients with diabetes. We were both thrilled and terrified at the prospect of being the first child to try a treatment such as this. Epalrestat showed promising results in Maggie’s fibroblasts but we wanted to make sure she would be safe, and we wouldn’t do any damage to her liver.


Luckily, the CDG communities has one of the best physicians, the vibrant and irreplaceable Dr. Eva Morava. Dr. Morava has served as the principal investigator for Maggie’s trial and helped us navigate this new world and monitor Maggie’s safety. Maggie’s liver function tests, AST (aspartate transaminase) and ALT (alanine aminotransferase) levels, have stayed steady throughout the trial. Additionally, her liver fibroscans have shown her fibrosis score in the F0-F1 level consistently.


We have not noted any negative side effects and Maggie takes her medicine like a champ! We have seen her transferrin levels normalize while on the drug. Prior to epalrestat, Maggie’s transferrin glycoform measurements, specifically the mono-oligo/di-oligo ratio in her blood, were always abnormal. As you can see on this chart, we’ve had our first normal readings in the normal range noted by the green dots. Maggie’s weight has increased while on epalrestat and she’s gained muscle and tone. You can see how she outgrew her dose at 9 months and how an adjustment to a higher dose helped re-normalize her transferrin glycosylation at 12 months.


A newly discovered biomarker was found to be elevated in Maggie along with about 70% of PMM2-CDG patients seen at Mayo Clinic. Maggie’s elevation of this biomarker normalized after 3-months of treatment and remained normal at 6 months when last evaluated.


We’ve seen impressive gains in Maggie’s stability, strength, gross and fine motor skills. One clear clinical data point that points to this is her ICARS scores. ICARS is the International Co-operative Ataxia Rating Scale and is a non-invasive evaluation completed by a neurologist. It looks at four areas of function including postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. Maggie does a series of tasks like slide the heel of her foot down her shin while laying on her back. The test is scored from 0-100 with a higher score indicating greater impairment. On epalrestat, Maggie’s score has steadily declined from 66 to 56 to 43.


Maggie continues to develop more and more remarkable speech improvements. Before epalrestat Maggie could communicate, but her vocabulary was limited, her enunciation was not great, and her ability to convey thoughts and ideas was minimal. Maggie can now use communication skills beyond just meeting her basic needs. She’s thoughtful, witty, and clever. I continue to be wowed by statements she says. Just last week, I was struggling to complete a basic task myself and Maggie cheered me on saying, “You can do it mommy! You are strong! You are a Carmichael!”. Her speech improvements have even given rise to a bit of a roguish streak to her. Now when asked about an obvious mess she made, she replies with an unconvincing “Hmm… I have no idea what you are talking about…” The volume of words she says, length of phrases, clarity and intelligibility of words have all improved along with processing speed, complexity of ideas and thoughts, and ability to discuss relevant topics and recall events.

Maggie’s strength and ability to safely get from point A to point B have also improved during the trial. She army crawled for most of her early life and began four-point crawling around age 5. This mode of transport brought with it a new challenge -- the face plant. Every single day she would face plant no fewer than three times. It broke our hearts. She was just trying to get somewhere, get something, or get someone and she would hurt herself. Almost overnight that went away and she got much faster. Given her desire to walk more and more, we’ve installed a long railing down the hallway that she regularly uses independently. She seems to have more stamina and energy, better balance and body control, and increased muscle volume.


She loves to color now and she colors so well! She’s also started drawing more and I shared a photo of her Elsa drawing she did on our drive back from our last Mayo trip. Her fine motor skills improvement has also helped her eat more independently and without such a mess! Sometimes I look at the gains as more things we don’t do anymore. Maggie doesn’t have to use her bath seat because her balance and stability is so much greater. We don’t tape down her papers to draw or color. We no longer feed her or clean up massive messes when she feeds herself. We no longer console her from face planting.


Because year 1 of the trial has completed, Maggie can now take a higher dose of epalrestat and already since beginning we feel like we’ve seen Maggie “level up.”


It’s hard to describe the overall benefit to Maggie’s life epalrestat has allowed. It is hard as a parent to watch your child struggle and you want to do everything in your power to help them. Seeing these gains has been so incredibly rewarding. I truly hope this treatment can help other kids experience gains in their quality of life and everyday activities. I was overjoyed when a Canadian parent who, shortly after Maggie began her n-of-1 trial, also began a single patient trial of epalrestat for their son with PMM2-CDG. A shared video of some of his first steps brought tears to my eyes. https://youtu.be/fV0X4dvBEnY

Their family has noticed some of the same gains we have in Maggie as far as speech, gross motor, and fine motor improvements.


Maggie’s Cure teamed up with Perlara to launch a new organization, Maggie’s Pearl.

Maggie’s Pearl is a biotech joint venture on a mission to develop the first platform therapy for CDG. Starting with launching a thirty-patient study of epalrestat in the treatment of PMM2-CDG in Q2 2021 we hope to help other families see quality of life improvements like we have in Maggie. You can check out our website at www.maggiespearl.co and sign-up to stay connected with any updates. Here are some brief details about the expanded trial, but please note these details are not yet confirmed and could change.


Who: 30 PMM2-CDG patients, ages 2-17, with abnormal transferrin and/or elevated biomarker What: Open label epalrestat trial, oral capsule, 4x daily When: Q2 2021 Where: Mayo Clinic How: Quarterly Visits, some visits will be through telehealth


Open label means that everyone who joins the trial will get the actual medicine and won’t get a placebo. One of the barriers we’ve heard about for participating in research and trials is the travel costs associated. Maggie’s Pearl is dedicated to helping ensure the trial is accessible for families and has travel vouchers available for the trial visits out to Mayo Clinic.


2020 brought some amazing progress for Maggie and we can’t wait to see what 2021 has in store! We are eternally grateful to everyone who has had a part in our journey and who has wished us well along the way.



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