A Voyager Therapeutics (VYGR) gene therapy delivered surgically, once, to the brain of a small number of patients with advanced Parkinson's disease is demonstrating early signs that it can improve motor function, according to interim results from a clinical trial announced Wednesday.
Voyager cannot cure Parkinson's patients with its experimental gene therapy because nothing yet invented is capable of bringing dead neurons in the brain back to life. What Voyager is developing, instead, is a one-time gene therapy that acts like a biological detour around dead neurons so Parkinson's patients respond better and longer to levodopa, the standard drug used to treat the progressive brain disease.
"What we're trying to do is turn back the clock in these advanced Parkinson's patients to a time early on in their disease where they had good motor control," explained Voyager CEO Steven Paul.
An advanced Parkinson's patient needing to take a whopping 1.5 grams of levodopa per day and still suffering from longer periods of muscle tremors and stiffness might, if Voyager is successful, be transformed into a mild Parkinson's patients where a fractionally lower levodopa dose improves motor function to nearly normal, Paul adds.
The new data reported Wednesday are encouraging but Voyager is nowhere near its ultimate goal yet because the company has only performed its gene therapy surgery on ten Parkinson's patients in this ongoing clinical trial. Just three of those patients, treated with what looks like the higher, more effective dose, have been followed for one year.
If you're not actually curing Parkinson's patients, how long and to what extent can you roll back the progression of their disease? That's an important question Voyager cannot yet answer. None of the data reported Wednesday includes a placebo control, either, which is important but won't happen until Voyager starts a different pivotal study late in 2017.
Voyager uses an inactivated, harmless virus to deliver a DNA sequence carrying genetic instructions to produce an enzyme known as AADC necessary to convert levodopa into dopamine, an essential neurotransmitter. Doctors perform brain surgery, guided by magnetic resonance imaging, to inject Voyager's gene therapy into the part of the brain called the putamen where dopamine is needed.
Ten patients with advanced Parkinson's, split equally, received a lower (first cohort) and higher (second cohort) dose of Voyager's gene therapy. The most striking data, albeit incomplete, came from patients treated with the higher, second dose of Voyager's gene therapy.
Surgeons placing Voyager's gene therapy were able to cover 34% of the putamen without any new surgical complications not previously disclosed. Following surgery, the activity of the AADC enzyme in the putamen increased 56% at six months compared to baseline. These patients were able to reduce their daily dose of levodopa by 34% and maintain that reduction out to 12 months.
In Parkinson's trials, changes in a patient's motor symptoms are measured during the period when levodopa is working (the on period) and when the drug is not working (the off period.) UPDRS-III is the standard test conducted by doctors to assess changes in Parkinson's motor symptoms.
Patients treated with the second, higher dose of Voyager's gene therapy saw a 17.8 point reduction, or improvement, in their UPDRS-III off medication score at 6 months, which decreased to 14.3 points at one year. [Three of five treated patients who have been followed long enough to report one-year results.]
The same patients reported a 9.6-point reduction, or improvement, in the UPDRS-III on medication score at six months, sustained at 12 months.
Patients also kept personal diaries to record the amount of time each day that their Parkinson's motor symptoms were under control. These results supported the same improvements seen with the UPDRS-III scores.
"What is particularly exciting about what Voyager is presenting is the predictable and consistent delivery of the gene therapy," said Todd Sherer, CEO of the Michael J. Fox Foundation, which raises money to fund research into Parkinson's.
Previous attempts at delivering gene therapy surgically to Parkinson's patients have not had the same level of success and validation in terms of being able to show the treatment getting to the right place in the brain and then demonstrating prolonged activity, Sherer added.
The Michael J. Fox Foundation provided seed funding to researchers at the University of California, San Francisco for early work on the gene therapy that was later taken over by Voyager.
Voyager will continue to follow the Parkinson's patients already treated and is in the process of recruiting additional patients for treatment with a higher dose. Four of a planned five patients have already been surgically implanted with that third, higher dose of the Voyager gene therapy without any complications. The next update from the study will be announced in the middle of next year.