In the United States, Orphan Drug designation is a special status granted to drugs or biologics intending to treat, prevent, or diagnose a rare disease or condition. A “rare” condition refers to one affecting fewer than 200,000 people within the country. This designation comes with a variety of incentives, including fee waivers, tax credits, and seven years of market exclusivity upon appoval. Ultimately, the FDA hopes that this will spur increased research and development into rare conditions and potential treatments. According to an article in Pharma Business International, Aro Biotherapeutics recently received Orphan Drug designation for its therapy ABX1100.
Aro Biotherapeutics explains that ABX1100 is:
a first-in-class Centyrin-siRNA conjugate that is designed to reduce glycogen levels in the muscle by inhibiting the expression of the enzyme responsible for glycogen production, glycogen synthase 1 (GYS1). A mouse cross reactive Centyrin-siRNA conjugate demonstrated robust and muscle-specific inhibition of the GYS1 gene in preclinical animal studies, which has led to significant reductions of glycogen in target tissues.
Aro Biotherapeutics hopes that ABX1100 could overcome some of the limitations associated with enzyme replacement therapy (ERT). In particular, it hopes to better treat and address issues with skeletal muscle tissue. While ABX1100 is not currently in clinical studies, researchers hope to begin research in humans by the end of next year.
About Pompe Disease
Pompe disease is a genetic disorder resulting from GAA gene mutations. Normally, GAA creates an enzyme called acid alpha-glucosidase (GAA). The body uses this enzyme to break down a complex sugar called glycogen. However, GAA gene mutations reduce or eliminate GAA production in those with Pompe disease. As a result, the body is unable to break down glycogen and it begins to accumulate in cells. This later causes impaired muscle function and other health issues, which can be life-threatening. Over 300 genetic mutations have been implicated in Pompe disease development.
The Three Subtypes
Classic infantile-onset Pompe disease typically manifests within a few months following birth. Without treatment, this form can be fatal within the first two years of life. Symptoms can (but do not always) include:
- Failure to thrive
- Hypotonia (low muscle tone)
- Difficulty eating
- Muscle weakness
- Difficulty breathing and/or frequent respiratory infections
- Poor neck and head control
- Developmental delays
- An enlarged liver, heart, and/or tongue
- Heart defects
There is also a non-classic infantile-onset form, which typically manifests later, around one year old. Symptoms are similar to the above, though muscle weakness and motor development may be progressive. Heart failure or heart problems are also less common in this form. Without treatment, those with this form may only live until early childhood.
Finally, there is late-onset Pompe disease. Symptoms may manifest in late childhood all the way through adulthood. Typically, this is considered a milder form and often does not involve the heart. Symptoms can (but do not always) include:
- Macroglossia (an enlarged tongue)
- Difficulty eating and/or swallowing
- Progressive muscle weakness
- Shortness of breath
- Abnormal spinal curvature
- Joint stiffness
- Enlarged liver
- Respiratory failure
