At the start of February, gene therapy company Spark Therapeutics (“Spark”) announced that the first participant in the RESOLUTE trial was dosed with SPK-3006. The trial is evaluating the investigational gene therapy for patients with late-onset Pompe disease. Altogether, around 20 patients will enroll in the study.
SPK-3006
The Phase 1/2 RESOLUTE trial will analyze the safety, efficacy, and tolerability of SPK-3006, an investigational adeno-associated viral (AAV) vector gene therapy. The therapy is administered intravenously. AAV works by transforming a natural virus into a delivery mechanism. According to AskBio:
The viral DNA is replaced with new DNA, and it becomes a precisely coded vector and is no longer considered a virus, as most of the viral components have been replaced. The AAV vector is then used to deliver normal copies of genes to the right tissues or organs in the body, but it now delivers the therapy that has been engineered into it.
Spark collaborated with Genethon to develop SPK-3006. The engineered therapy produces a modified version of gene encoding acid alpha-glucosidase (GAA); normally, this enzyme is limited in patients with Pompe disease. This prevents the breakdown of glycogen and increases negative health impacts. Thus, by raising GAA levels, SPK-3006 could ultimately improve patient outcomes.
Pompe Disease
GAA gene mutations cause Pompe disease, a genetic lysosomal storage disorder that prevents the body from breaking down glycogen. As this complex sugar builds up in the body, it impacts the way that muscles, tissues, and even organs function. An estimated 1 in 40,000 Americans has Pompe disease.
There are three major forms of Pompe disease: classic infantile-onset, non-classic infantile-onset, and late-onset. In classic infantile-onset Pompe disease, symptoms appear within a few months of birth. Without treatment, this form is often fatal within 2 years. The current treatment is usually Myozyme, a GAA replacement treatment. Symptoms of classic infantile-onset Pompe disease include:
- Muscle weakness
- Low muscle tone
- Heart and respiratory problems
- Failure to thrive
- Feeding difficulties
- Liver enlargement
In the non-classic infantile-onset form, symptoms usually do not appear until the child turns one. While heart failure is less common in this form, many children often only live to early childhood. Symptoms include:
- Progressive muscle weakness
- Motor skill delays
- Abnormally large heart
Finally, late-onset Pompe disease may appear from late childhood through adulthood. However, some medical professionals will also use “late-onset” to describe whether or not the heart is affected. Unlike other forms, late-onset Pompe disease is much less likely to affect the heart. Symptoms include:
- Progressive muscle weakness
- Unintended weight loss
- Irregular heartbeat
- Difficulty hearing
- Muscle pain
- Frequent lung infections and/or difficulty breathing
- Exercise intolerance
Learn more about Pompe disease here.
