'Voyager' Recruits Patients for Gene Therapy Delivery Voyager Therapeutics announced it is recruiting participants for the company’s new Phase 1 clinical trial to test a new approach for their gene therapy VY-AADC01 in Parkinson’s patients. 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 ongoing 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 focus on assessing the level of AADC produced and how active it is in the putamen, which is 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 now needs to be tested in a double-blind fashion. Voyager is very keen to move ahead with VY-AADC01. The company will continue to follow cohorts 1,2 & 3 from the first trial over the long term. The next trials are now recruiting. Subjects involved in the study all have advanced Parkinson’s disease so it is good to see trials which can potentially benefit later stage subjects. Our ability to delivery of 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. Thanks to Simon Stott - The Science of Parkinsons.