Is AADC gene therapy a valuable option for patients with moderately advanced Parkinson Disease?

In this work, the authors studied whether VY-AADC01 (NBIb-1817) gene therapy was safe and effective in patients with moderately advanced Parkinson's disease (PD) patients with motor fluctuations. The authors showed that this treatment caused an improvement in motor function, quality of life, and a decrease in the level of PD medication administrated. 

Parkinson's disease (PD) is a disorder in which part of the brain is damaged over the years. This leads to an involuntary shaking of particular parts of the body (tremor), slow movements, and stiff and inflexible muscles. 

The treatments available for PD are only able to relieve symptoms. A common treatment is levodopa/carbidopa (Sinemet). This drug is absorbed by the nerves and is transformed into dopamine, a molecule that controls movements, by a protein called L- amino acid decarboxylase (AADC). In PD, the neurons that possess AADC degenerate, and, in time, higher doses of levodopa are required to produce dopamine. 

Gene therapy is a technique that works by providing cells the information they need to work properly. This is done for example by replacing a faulty gene with a functional one. One way to deliver the working gene is by using viral vectors (inactive viruses). 

NBIb-1817 (VY-AADC01) is a type of gene therapy that uses a virus (adeno-associated virus serotype 2, AAV2) as a delivery system. The virus is modified in order to deliver the gene for AADC protein. The virus should deliver this gene only in a specific area of the brain where there are AADC neurons, allowing the production of dopamine from the levodopa drug. Whether VY-AADC01 gene therapy is safe and effective in patients with advanced PD is still under investigation. 

In this phase 1b trial, 15 patients with moderately advanced PD were included. There were 3 groups of patients that received VY-AADC01 delivered to the brain in 3 increasing doses. The study lasted for a total of 3 years.

The VY-AADC01 drug was well-tolerated by patients. Overall, 2 participants reported 4 severe side effects that were resolved and were not related to the treatment. Common side effects included headaches and transient dyskinesia (involuntary movements of the face, arms, legs, or trunk).

At the end of the trial, the amount of levodopa administrated to patients decreased by 21-30% in the 2 highest dose groups (groups 2 and 3), while it remained stable in group 1. 

Movement function, global impressions of improvement, and quality of life remained stable or improved by the end of the treatment. 

This study showed that VY-AADC01 was well-tolerated and resulted in stable or improved movements and quality of life. It also reduced PD medication requirements in higher doses over 3 years. 

This study included a very small number of participants. Larger studies are needed to confirm these results. This study received funding from Voyager Therapeutics, Inc., and Neurocrine Biosciences, Inc., the manufacturers of VY-AADC01.