Gene Therapy Is an Exciting Step in the AADC Deficiency World

A columnist reflects on what led to the approval of Upstaza for AADC deficiency

Richard E. Poulin III avatar

by Richard E. Poulin III |

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In December 2018, my wife and I discovered our daughter, Rylae-Ann, had a rare, genetic disease known as aromatic l-amino acid decarboxylase (AADC) deficiency. We didn’t know much at the time, but we quickly learned there were no treatment options.

That’s now changing, however, as medical innovations have opened the door to gene therapy.

First disease-modifying therapy for AADC deficiency

Leading the charge is Upstaza (eladocagene exuparvovec), a gene therapy being developed by PTC Therapeutics.

The European Commission approved Upstaza for AADC deficiency patients in July, and the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA) made a similar decision just last month. Both agencies approved the therapy for patients 18 months and older.

Our daughter was fortunate to receive gene therapy treatment on Nov. 13, 2019, as part of a clinical trial in Taiwan. She was only 18 months old, and I believe her age was a big factor in her dramatic results.

A photo depicts the silhouette of a woman and her young daughter walking on the beach at sunset. They are standing in shallow water, and the photo is taken at a low angle, making it appear as though they're walking on water. The woman is wearing a T-shirt and pink shorts, and the young girl is pointing toward the horizon.

The results of gene therapy are a miracle, the author says — like walking on water. (Photo by Richard E. Poulin III)

As other gene therapies are investigated, a key feature will be the ability to treat patients at a young age. To achieve success in developing new treatments for AADC deficiency, pharmaceutical companies might follow the example set by PTC’s development of Upstaza.

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Trial location

The clinical trial we enrolled Rylae-Ann in took place in Taiwan, and for good reason. Only about 135 cases of AADC deficiency have been described worldwide since 1990, but Taiwan has the highest prevalence. By conducting the trial there, researchers had a better chance of enrolling more people.

Clinical trials come with eligibility requirements. Within an already limited pool of people, these criteria further limit how many people can participate. One requirement of this trial was that families stay nearby for safety and data collection, the latter of which is a key purpose of clinical trials.

Normally, regulatory agencies need data from a large population to approve new treatments or therapies, but that isn’t possible with rare diseases. Thankfully, they’ve developed alternate paths to approval for these small, rare communities. But data are still necessary to this process, so every person involved in a trial plays a substantial role.

If the clinical trial had been conducted elsewhere, many families would face the added barrier of traveling and have a harder time committing. Even though the majority of families involved in this study lived in Taiwan, the COVID-19 pandemic made it difficult for many to return to the clinic to submit data.

Data collection

The data collection process was thorough and involved many tests. It was difficult to subject our daughter to all of them, as she struggled with a lot of anxiety surrounding hospitals. However, we knew the testing was important, so we continued to contribute.

Another challenge was being unable to talk publicly about the trial or communicate with other families involved while it was ongoing, as it might’ve affected the data.

For the same reason, we couldn’t make any claims or share any success stories. One example of this is how, from our perspective, our daughter no longer experienced oculogyric crises (OGCs) after receiving gene therapy. However, based on the doctor’s review, she was still having OGCs, because when she was tired or had had a long day, she’d exhibit fleeting upward glances. The episodes just looked completely different from the episodes she experienced before gene therapy. With doctors setting the definition, we can maintain consistency and make valid claims about the effectiveness of gene therapy.

Presenting accurate data to regulatory agencies was a crucial part of Upstaza’s approval in Europe and the U.K. My wife and I were also able to share our perspective with the European Medicines Agency and MHRA as part of the approval processes.

Looking to the future

It can be difficult for rare disease communities to encourage pharmaceutical companies to invest in research and develop therapies that will benefit a relatively small number of people. But the approval of Upstaza in Europe and the U.K. shows it’s possible and will hopefully encourage more innovation.

PTC Therapeutics is now seeking approval of Upstaza from the U.S. Food and Drug Administration, and researchers are investigating ClearPoint Neuro’s SmartFlow Cannula device to improve delivery of the gene therapy. Future studies may involve in vitro gene therapy, robot-assisted surgery, and cell therapy.

I look forward to seeing how future medical innovations will continue to benefit our children.

Note: AADC News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of AADC News or its parent company, BioNews, and are intended to spark discussion about issues pertaining to aromatic l-amino acid decarboxylase deficiency.