A-dopamine pump extends on time for Parkinson’s patients
DIVE-I study compared A-dopamine with oral treatment
Parkinson’s disease patients saw an average increase of more than four hours in the duration of their symptom control, without the presence of dyskinesia, with a consistent supply of A-dopamine directly to their brain, according to a small Phase 1/2 clinical study.
DIVE-I (NCT04332276) tested how safe A-dopamine, a stable form of dopamine that’s depleted in Parkinson’s, is compared with oral dopaminergic treatment and how well it works when delivered by a pump via a surgically implanted catheter directly into the striatum, a brain region involved in motor control. Dyskinesia is a common side effect associated with levodopa, one of the standard treatments for Parkinson’s.
No serious side effects were reported, but higher doses caused transient nausea or vomiting, drowsiness or sedation, and low blood pressure in some patients. Everyone who completed the study chose to continue taking A-dopamine.
“We are doing our utmost to confirm these results as quickly as possible on a larger scale, with a Phase [3] program that will guarantee the fastest possible market access by the end of this decade under early accesses, and by the very beginning of the next decade for a full access,” Véronique Foutel, InBrain Pharma’s CEO, said in a company press release.
The study, “Intracerebroventricular anaerobic dopamine in Parkinson’s disease with L-dopa-related complications: a phase 1/2 randomized-controlled trial,” was published in Nature Medicine. It was funded by InBrain.
Parkinson’s is caused by the loss of dopaminergic neurons, the nerve cells in the brain that produce dopamine, a chemical needed for motor control. Loss of dopamine causes motor symptoms, such as tremor, stiffness, problems with balance, and slowed movements, called bradykinesia.
Because dopamine is unstable and can’t cross into the brain, its precursor, levodopa, remains a mainstay treatment for Parkinson’s. However, with age and as the disease progresses, patients may need higher doses more frequently. This can lead to motor fluctuations, when symptoms aren’t well controlled.
A new approach to controlling Parkinson’s symptoms
With A-dopamine, InBrain is addressing two challenges: keeping dopamine stable and delivering it steadily to the striatum using a small pump placed in the abdomen in the absence of oxygen, which is thought to make dopamine less stable. The pump is connected to a catheter implanted near the striatum, providing a steady supply of A-dopamine.
Clinical testing at Lille University Hospital in France included 12 patients (nine men, three women), who were a median age of 60.8 and had a median disease duration of 7.9 years. They’d been having motor fluctuations for a median of 4.3 years and dyskinesia, or uncontrolled movements, for a median of 2.4 years.
The procedure to implant the catheter in the brain and tunnel it under the skin to the abdomen was done under general anesthesia, lasting less than four hours. By the afternoon, patients could walk easily, with only mild abdominal pain, and they needed minimal or no painkillers. The pump was refilled every 7-15 days.
In Phase 1, A-dopamine was found to be safe, with no serious side effects. The Phase 2 part compared A-dopamine with optimized oral dopaminergic treatment in nine patients over two months. Each patient received one treatment for a month then switched to the other.
The main goal was to measure how much time patients spent with dyskinesia or bradykinesia, tracked using a wristwatch at home. A-dopamine resulted in an average gain of 4.4 hours of on time, when motor symptoms are well controlled, and an average gain of 6.6 hours of functional autonomy each day. Home diaries confirmed better symptom control with A-dopamine.
“These initial results underline the full potential of this new dopamine-based device-assisted therapy (DAT),” said David Devos, MD, PhD, and Caroline Moreau, MD, PhD, who led the study. The treatment could offer “an alternative not only to patients who have failed current therapies, but also to those who are not considering treatment with available DATs. In addition to demonstrating the benefits for Parkinson’s disease, this work also validates the concept of cerebral infusion as a personalized treatment for other neurological pathologies,” they said.
Devos and Moreau co-founded and serve as scientific advisors for InBrain.
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