n=1 trial for the treatment of PMM2CDG 6-mo Update
Disclaimer: I’m mom to Maggie, age 6. This post is based on my interpretation of Maggie’s progress and should not be taken as medical advice. You should consult with your Dr about any treatment options or available drug trials.

A little over 6 months ago Maggie began taking 5mg of epalrestat 3x daily in a Compassionate Use Single Patient IND Trial. Epalrestat is a 30yr old generic Japanese drug and aldose reductase inhibitor used in geriatric patients with diabetes to treat peripheral neuropathy.

Peripheral neuropathy is often associated with PMM2-CDG and something Maggie has at a moderate level. @PerlaraPBC and @eperlste team built small model organisms and conducted high throughput screening to find this drug https://dmm.biologists.org/content/12/11/dmm040584.

Through the IND, @EvaMorava discovered a new biomarker for PMM2-CDG patients. Its level is elevated in 70% of PMM2-CDG patients seen at the Mayo Clinic and has not been previously reported. Epalrestat has brought Maggie’s elevated level of this biomarker to a normal range.

To say we’ve seen a positive impact in Maggie’s quality of life would be an understatement. The evidence is so overwhelming that I think I can finally allow myself to be excited and happy about her progress and shout it from the rooftops! Here is a summary of progress we’ve seen:

Maggie’s speech has exploded. I can have conversations with her! She talks about relevant topics with a larger vocabulary. Her response times have improved with less processing delay in conversational exchange. The complexity of thought behind her communications continues to wow.

6: Mommy, what are you doing?
Me: Playing a game with daddy
6: Can I play?
Me: No sweetie, you’re not old enough.
6: Mommy, I am 6 yrs old. You have to be 5 yrs old to play.
The processing requirements to set a fabricated age limit that was less than her age is astonishing!

Maggie was cleaning her room and came out with something in her hand.
6: Mommy, you won’t believe what I found in my room.
Me: What is it?
6: It’s a screwdriver.
It was a screw, but the amazing thing to me is her sentence structure and use of the phrase “you won’t believe”.

She’s talking about relevant topics, her dad is ordering her and her brother a basketball hoop. She asks him each day, “Daddy, how many days until my new basketball hoop gets here?”. These sentences are so long and complex and beyond anything like her speech was before.

Maggie’s fine motor has steadily improved. Most striking is her coloring. She only scribbled before but now colors in the lines! To great detail! You can see before and after pictures in this post. It stopped me in my tracks when I looked at the pictures she’s colored.

She’s also drawing much better. Again – before drawings were just scribbles. Now there are recognizable things that are relevant to and reflective of her life. See this image she drew of Dan. Letter formation is less shaky and clearer with smoother lines.

This picture she drew after helping prepare scrambled eggs. While cleaning up from breakfast, Maggie opted to sit at her desk to do some free drawing and actually drew out what she had just done with no prompting. She described her drawing in detail afterwards.

Maggie 4-point craws around the house and used to face-plant 5-6x daily. Then she’d cry and it was a miserable thing to see. She now has 0 faceplants! This quality of life gain has such a huge impact on her daily life.

Maggie has improved greatly on her bike. She switched from a bike w/a handle in the back that we would push for her. She was not able to peddle on her own. She can make that thing go, can steer and is even doing some riding without being buckled!!

She’s asking to walk more and more and we’re able to hold lower on her body to support her – at her pelvis vs. trunk or arms. We’ve installed a railing down the hallway that she now uses multiple times per day and will lift one leg up in what she calls a “ballerina” move.

She’s more stable & can sit on the edge of the ottoman and balance (without hands) while I brush her hair. Before, Maggie needed both hands to support her to sit on the ottoman and even then we would need to be near her to “spot” her.

She’s getting dressed more independently & has more energy & is more active. Her use of her gait trainer has improved & we can now use that as her main mode of transportation at Mayo. Check out this video – note Maggie began use of epalrestat 1/29/20.

Her transferrin levels are NORMAL! Maggie has never had a normal result until this last one. Transferrin is a common test done in CDGs. Transferrin does typically normalize in PMM2-CDG patients, but this is usually happening after puberty.

She’s seemed to have better growth. We notice thicker legs and her IGF-1 (a growth hormone) results have gone from 83 to 111 and Z-Score (standard deviation from 50th percentile) has improved from -0.84 to -0.39. Chart is with no change in diet.

Her liver function tests and fibroscan results have remained stable and she does not appear to have any negative side effects of the medication.

It seems very possible, that based on Maggie’s results, there will be an expanded trial to allow other patients (likely age 4-17) to take epalrestat and see if there is safety and improvements. My greatest hope is that others can experience some of these amazing gains.

Many gains are difficult to measure and hard to know what’s a drug’s effects and what is natural development but to my fellow parents– sometimes you just know. Maggie wasn’t making these types of gains before and I truly believe that this major jump is because of epalrestat.

Additionally, lab results are improving as well and although the natural history of PMM2-CDG is not yet thoroughly studied and documented, I think that these things aren’t part of the typical course.

If you think you might be interested in the expanded trial, my advice (as a parent) is to enroll in the natural history study through FCDGC by e-mailing @EvaMorava at [email protected]. You should also get fibroblasts collected if you haven’t done so already.

I’m hoping to host a webinar Sept17 to go through our experience and have lots of Q&A time for any families about different aspects of clinical trials or drug discovery. I’m not giving up that we can cure CDG. This is just one small step towards that dream.

#GoMaggieGo