Top 10 Pompe Disease Stories of 2022

Gene therapy was the focus of half of the best-read stories this year

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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In 2022, Pompe Disease News brought you weekly coverage of the latest scientific research, clinical trial updates, and treatment advances related to Pompe disease.

We look forward to continuing to be a resource for our valued readers in 2023. Here is a list of the 10 most-read Pompe news articles from 2022, with a brief description of what made them relevant for the Pompe community.


No. 10 – Brain Blood Flow Changes May Be Complication of LOPD

The case of a 39-year-old man in China with late-onset Pompe disease (LOPD) who experienced stroke-like symptoms highlighted that abnormalities in brain blood flow could be an under-recognized complication of the rare genetic disorder.

The man’s symptoms were found to be due to brain blood flow changes, according to the report, published earlier this year.

A modified diet and treatment with the enzyme replacement therapy (ERT) Lumizyme (alglucosidase alfa), along with blood thinners and fat-lowering medications, were beneficial.

Researchers noted that brain blood flow abnormalities, while rarely observed in LOPD, have been documented in other reports.

No. 9 – Europe OKs Nexviadyme for Infantile- and Late-onset Disease

In June, the European Commission (EC) approved Sanofi Genzyme’s Nexviadyme (avalglucosidase alfa), a next-generation ERT, for the treatment of LOPD and infantile-onset Pompe. It was the first time a new Pompe treatment had approved in Europe since 2006.

Designed to deliver a working copy of the acid alpha-glucosidase (GAA) enzyme that’s deficient in Pompe, Nexviadyme aims to improve GAA delivery to the muscles compared with Lumizyme (marketed as Myozyme in Europe), the first ERT approved for Pompe.

The EC’s decision was supported by data from the ongoing COMET (NCT02782741) and Mini-COMET (NCT03019406) clinical trials, which are testing the therapy in LOPD and infantile-onset Pompe, respectively. COMET is expected to be completed in 2023, with Mini-COMET slated to wrap up in 2024.

The therapy already had been approved in the U.S. and some other countries, where it is marketed as Nexviazyme.

No. 8 – Certain Modifications May Improve Efficacy of Pompe Gene Therapies

A study using a new cell culture model of Pompe found that by fusing a therapeutically delivered GAA enzyme to certain peptides — short chains of amino acids, the building blocks of proteins — the enzyme could be more effectively secreted and taken up by neighboring cells.

When delivered to cells via a viral carrier  — a common way of packaging gene therapies — the peptide-fused enzyme had a greater ability to restore GAA levels. Secretion of GAA from the cells that took it up also was increased, enabling the healthy enzyme to then reach others nearby that the treatment had initially missed.

Overall, these findings could offer ways of enhancing the therapeutic potential of gene therapies for Pompe, a number of which are now under investigation.

No. 7 – Antioxidant-rich, Ketogenic Diet Boosted ERT Benefits in Mice

A diet containing an oral ketone precursor — being studied as a dietary supplement — and a cocktail of antioxidant molecules made ERT more effective in a mouse model of Pompe. Mice that received the combination saw better maintenance of muscle strength and motor function, as well as improvements in cellular processes implicated in Pompe.

The ketone precursors and antioxidants were able to lower oxidative stress, a type of cellular damage, and boost autophagy, a cellular defense against oxidative stress. Autophagy also is key for fighting the accumulation of glycogen, the complex sugar molecule that builds up in cells as a consequence of GAA deficiency in Pompe.

More studies are needed to better understand the safety profile of ketone precursors, the researchers noted.

No. 6 – Stem Cell-based Gene Therapy Eliminates Symptoms of Pompe in Mice

Another study using a mouse model of Pompe found that a stem cell-based gene therapy was able to normalize the buildup of glycogen in various tissues, in addition to restoring cellular defects and improving motor function.

Briefly, the treatment involves collecting hematopoietic stem cells, which give rise to all blood cells, from a patient’s bone marrow and exposing them to a viral carrier containing a healthy copy of the GAA gene that’s faulty in Pompe. The modified cells are then returned back to the patient.

According to the researchers, the findings demonstrate the potential of such a gene therapy for correcting the defects associated with Pompe. These results prompted the team to recommend the approach for future clinical development.

No. 5 – MZE001 Wins FDA Orphan Drug Status for Pompe Disease

The U.S. Food and Drug Administration (FDA) awarded orphan drug designation in late August to MZE001, Maze Therapeutics‘ investigational oral treatment for Pompe.

The designation intends to speed the development of treatments for rare diseases by offering financial incentives and regulatory support, as well as marketing exclusivity should the therapy be granted approval.

MZE001 is a substrate reduction therapy that works to lower the production of glycogen by suppressing an enzyme needed to produce the sugar molecule in muscle cells. The company believes the treatment has potential as a monotherapy for LOPD patients, but could also be used in combination with ERT for patients across the disease spectrum.

No. 4 – Maze Raises $190M, Gears Up for First Clinical Testing of MZE001

Prior to MZE001’s orphan drug designation, Maze announced plans to begin clinical testing of the investigational treatment in the first half of the year. That news came after $190 million was raised by the California-based company to support its clinical programs.

A Phase 1 trial (NCT05249621) to evaluate the therapy in healthy volunteers began dosing in February.

This year’s top three stories in Pompe disease all revolved around gene therapies.

No. 3 – AT845 Gene Therapy Showing Safety in Ongoing FORTIS Trial

Interim data announced by Astellas Gene Therapies indicated that the developer’s investigational gene therapy, AT845, was safe in four adults with LOPD who were treated in the FORTIS Phase 1/2 clinical trial (NCT04174105).

At the time of the announcement in February, two patients had been given a low dose of the one-time therapy, while two others received a high dose. The earliest treated patients had been followed for about six months, with no serious side effects reported.

AT845 works by delivering a healthy working copy of GAA to muscle cells.

No. 2 – FDA Places Clinical Hold on FORTIS AT845 Gene Therapy Trial

The FDA placed a hold on the FORTIS trial in early summer after one patient developed peripheral sensory neuropathy, a complication marked by nerve damage outside of the brain and spinal cord.

While the side effect was mild, it was deemed serious due to its medical implications. The FDA asked for more information before the trial could be unpaused.

It has not been announced if or when the trial will resume.

No. 1 – #MDA2022 – Gene Therapy ACT-101 Boosts GAA Levels in Early Trial

An investigational gene therapy from Asklepios BioPharmaceutical (AskBio) was well-tolerated among three LOPD patients treated in a Phase 1/2 clinical trial (NCT03533673).

Called ACT-101, the therapy works to provide a healthy version of GAA to the liver using a specially engineered viral vector. This allows the body to use the gene to make its own functional GAA enzyme.

Data presented at a conference in March demonstrated that all three patients showed no signs of lung function or motor decline six months after receiving the gene therapy. Based on those findings, all three participants were able to remain off ERT treatment for the remaining six months of the trial.

GAA levels had also increased markedly in muscle tissue and blood. Safety data indicate the treatment was generally well-tolerated.

The trial, which is estimated to recruit about 13 total participants, is still ongoing, with an expected completion date of April 2028.


At Pompe Disease News, we hope these stories and our upcoming coverage in 2023 contribute to informing and improving the lives of those affected by Pompe.

We wish all our readers a happy 2023!