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Turning the tide for rare disease

Turning the tide for adult polyglucosan body disease (APBD)

By Geoff Case

A $99,025 grant from the University of Pennsylvania’s Million Dollar Bike Ride (MDBR) enables pilot research into a promising new therapeutic for adult polyglucosan body disease (APBD). Resulting from a powerful partnership with the APBD Research Foundation, the grant creates hope for a turn in the tide for the APBD community

APBD: an ultra-rare neurodegenerative disease

APBD is an ultra-rare neurodegenerative disease. Its symptoms include progressive neurogenic bladder and bowel, numbness and tingling in extremities, weakness and fatigue. The disease is an adult-onset form of glycogen storage disease type IV and is caused by recessive mutations in the glycogen branching enzyme gene (GBE1).

Glycogen branching enzyme (GBE1) is an important enzyme involved in building the sugar storage molecule glycogen, and insufficient GBE leads to the formation of abnormal glycogen clumps called polyglucosan bodies. In APBD, polyglucosan bodies build up in the central and peripheral nervous systems and drive disease progression.

APBD community members rally for the Million Dollar Bike Ride

Harriet Saxe is a member of the APBD Research Foundation’s board of directors. She explains that “the foundation’s mission is to improve the diagnosis and treatment of APBD patients, support individuals and families affected by the disease, and increase awareness of APBD among health professionals and the public.” 

In June 2021, for the sixth year running, the APBD Research Foundation rallied a group of 89 community members to become the APBD Tour de Friends biking team and ride in the Million Dollar Bike Ride. In the midst of the pandemic, the ride was completed virtually in participants’ neighbourhoods, gyms and homes, as their abilities and options permitted. 

The group raised almost $70,000 and were delighted to then receive an additional $30,000 in matched funding from the Orphan Disease Center, who are able to do this through the philanthropic funds they receive. 

Harriet says, “Our partnership with the Orphan Disease Center’s Million Dollar Bike Ride has yielded critical research advancements for APBD in past years by funding nine research grants.” With these successes in mind, the organisation was hopeful that the 2021 MDBR would have a similarly happy outcome. 

After the ride, as in previous years, APBD researchers worldwide were invited by the Orphan Disease Center to submit proposals for grant support, and in early February the APBD Research Foundation was thrilled to hear that a proposal for research into the condition had won a grant of $99,025.

A grant to support research into a novel therapeutic for APBD

The winning proposal came from Prof Wyatt Yue, a professor of structural biology at Newcastle University in the UK, where he leads a team of researchers as a part of the Newcastle Structural Biology Laboratory. Prof Yue’s proposal—with the title “Discovery of glycogen synthase inhibitors for validation as a novel therapeutic target for adult polyglucosan body disease”—outlines the development of a novel therapeutic for APBD.

The novel therapeutic focuses on a strategy that has shown promise: reducing the activity of an enzyme called glycogen synthase (GYS1), which is involved in the process of making glycogen. Prof Yue’s research proposal describes the development of a small molecule drug that reduces glycogen synthase activity to prevent polyglucosan body build up. The small molecules to target the enzyme will be designed “using cutting-edge computational and screening methods”, Prof Yue says.

A $99,025 grant from the University of Pennsylvania’s Million Dollar Bike Ride (MDBR) enables pilot research into a promising new therapeutic for adult polyglucosan body disease (APBD
 Prof Wyatt Yue

“Our vision is to develop a daily pill for APBD patients as a transformative oral therapy. In the first step towards this goal, we aim to develop small molecules that act on the glycogen synthase enzyme as a drug starting point. We will take advantage of our unique knowledge about the shape of the glycogen synthase enzyme, which helps us identify the best region in the enzyme to target.” 

Moving together towards a brighter future

Harriet looks forward to a brighter future for the APBD community. A future shaped by the successful partnership of the APBD Research Foundation and the Orphan Disease Center, and by global research efforts, including those at Newcastle Structural Biology Laboratory: “We are so grateful for the commitment of the Orphan Disease Center and of researchers like Prof Yue to moving us closer to a world without the devastating effects of APBD and allied disorders.”

The community is also eagerly looking forward to 11 June 2022 when the APBD Research Foundation will again participate in the Million Dollar Bike Ride. Once again this will bring the wonderful APBD community together to accelerate research and help to turn the tide for the people with the condition.


To learn more about APBD and the APBD Research Foundation, please visit: www.apbdrf.org

To learn more about the Orphan Disease Center, please visit: www.orphandiseasecenter.med.upenn.edu


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