'Voyager' Recruits Patients for Phase 2 Gene Therapy Delivery Voyager Therapeutics recently announced it is recruiting participants for the company’s Phase 2 clinical trial testing the safety and effectiveness of the gene therapy VY-AADC02 in people with advanced Parkinson’s disease. Gene therapy is a technique that involves inserting new DNA into a cell using a virus as a vector. The DNA can help the cell to produce beneficial proteins that go on help to alleviate the motor features of Parkinson’s. Voyager Therapeutics is a clinical-stage gene therapy company that is focused on treatments such as Parkinson’s disease (PD). In September 2017 the company announced positive results from its Phase 1b trial of their product VY-AADC01. Voyager's gene therapy product, VY-AADC01, is an adeno associated virus that carries a gene called Aromatic L-amino acid decarboxylase (or AADC). AADC is the enzyme that converts L-dopa into dopamine. L-dopa can be naturally produced in the brain from Tyrosine which is absorbed from the bloodstream. It is also the basic component of many treatments for PD. By injecting the virus carrying VY-AADC01 into the putamen of people with advanced Parkinson’s disease, Voyager is hoping to alleviate the motor features of the condition by allowing the brain to produce a constant supply of dopamine in the exact location that is missing the dopamine - the putamen is where dopamine is released in the brain. This approach will not cure the disease, but it may make life a lot easier for those affected by it. The primary objective of the first study was to test the safety of VY-AADC01 in humans and determine how far the virus spreads once it is injected into the putamen. The secondary objectives focused on assessing the level of AADC produced and how active it was in the putamen, measured by positron emission tomography (PET) brain imaging. The results of the Phase 1b suggested that the virus was well tolerated and resulted in increased AADC enzyme activity, enhanced response to L-dopa treatment, and clinically meaningful improvements in various measures of patients’ motor function (44% improvement in ‘off medication’ measures and 55% improvement in ‘on medication’ measures). The researchers conducting the study were also interested to see if the product had any impact on the motor features of PD and so they took measurements of motor function and activities of daily living (using the Unified Parkinson’s Disease Rating Scale or UPDRS). One of the most interesting results in the first study was the physician-rated motor examination which suggested that while the cohort on the lowest dose of VY-AADC01 treatment did not improve, the members of cohort 2 and 3 (the higher doses of the virus) demonstrated remarkable improvements (that is a reduction in UPDRS scores). Note that these improvements were observed while the participants were on their medication, but remember that all three groups were reducing their medication during this time. This result suggests that the placebo effect may have been in effect in cohort 1. The change in UPDRS scores in cohort 2 & 3, however, is impressive at an 8 to 9 point reduction. The important point to remember in the first phase I trial of VY-AADC01 was that the study was ‘Open label’. This means that everyone involved (participants and clinicians) knew who was receiving the treatment. VY-AADC01 is now going to be tested in a double-blind fashion. The Phase 2 clinical trial testing the safety and effectiveness of the gene therapy VY-AADC02 in people with advanced Parkinson’s disease is now recruiting patients at select sites in the U.S. Hackensack University Medical Center is among 17 institutions across the U.S. enrolling up to 40 patients ages 40 to 75 , all diagnosed four or more years ago, for the double-blinded RESTORE-1 (NCT03562494) study. Subjects involved in the Phase 2 study all have advanced Parkinson’s disease so it will be interesting to see trials which can potentially benefit later stage subjects. Our ability to deliver genes to different locations shows just how far we have come with our understanding of the biology of PD and gene therapy is one treatment approach which is very exciting.