Recently, biopharmaceutical company PTC Therapeutics, Inc. performed a five-year data analysis to evaluate the continued safety, efficacy, and tolerability of PTC-AADC. The company developed this novel gene therapy to improve outcomes in patients with aromatic L-amino acid decarboxylase (AADC) deficiency. In a late September 2021 news release, PTC Therapeutics shared that the data analysis highlighted how PTC-AADC improved motor function and cognition in these children.
Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency
As explained above, PTC Therapeutics developed their gene therapy for patients with AADC deficiency, a rare genetic disorder characterized by low L-amino acid decarboxylase activity. Normally, this enzyme helps the body to produce serotonin and dopamine, which are neurotransmitters. These neurotransmitters help nerve cells communicate with each other. DDC gene mutations cause AADC deficiency. These mutations prevent the enzyme from performing its normal jobs, causing nerve cells to be unable to communicate. Ultimately, patients with AADC deficiency have low levels of epinephrine, norepinephrine, serotonin, and dopamine, which manifest in a variety of symptoms.
AADC Deficiency Symptoms
Symptoms of AADC deficiency are often not present at birth but will develop within a few weeks to months. Unfortunately, symptoms may result in complications; AADC deficiency is often fatal, with many individuals not living through childhood. Those with mild symptoms may reach adulthood. However, there is an urgent need for effective therapeutic options. When symptoms appear, these may include:
- Developmental delays
- Tremors
- Drooping eyelids
- Hypotonia (poor muscle tone), particularly in the trunk
- Hypertonia (abnormally high muscle tone) in the extremities
- Oculogyric crisis, in which uncontrolled head/neck movements, irritability and agitation, muscle spasms, and gaze deviation occur
- Diarrhea or constipation
- Hypokinesia (loss of muscle movement)
- Dystonia
- Uncontrolled and involuntary writhing movements
- Excessive sweating and salivation
- Congestion
- Low blood pressure and blood sugar
- Seizures
- Decreased or increased sleep and reflexes
- Behavioral problems
Doctors and researchers believe that AADC deficiency is widely underdiagnosed. Patients may be misdiagnosed as having certain forms of rare epilepsy or cerebral palsy.
PTC-AADC
PTC-AADC is a novel gene therapy which delivers a working DDC gene to patients. Earlier this year, AADC News described the treatment as:
surgically injected into the putamen, a brain region responsible for producing most of the dopamine in the brain. A modified and harmless adeno-associated virus carries the therapeutic gene into cells, where it integrates into the genome to become a regular part of each patient’s complete set of genes.
The treatment only requires one dose to be effective. PTC Therapeutics’ researchers recently released five-year study results on PTC-AADC, which utilize findings from three separate clinical trials. Findings include:
- When patients first began the clinical trials, many had issues with motor function and cognitive skills. For example, many patients struggled to sit, stand, or hold their heads up without additional support. Others were unable to freely communicate.
- Following PTC-AADC treatment, patients were able to perform these functions – sitting, standing, walking, and communicating – with some support. Patients, even as young as 3 months old, saw motor improvements. Many also saw improvements in language and communication skills.
- Finally, PTC-AADC treatment reduced rates of respiratory infection and helped patients gain weight.
These results are promising and could greatly assist patients and their families moving forward. By the end of 2021, researchers hope to receive approval for PTC-AADC in Europe, as well as submit a Biologics License Application (BLA) in the United States.
