Allosteric Modulator Alleviates Parkinsonism in Primates

[Farooqji]

This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l‐dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials.

onlinelibrary.wiley.com/doi...

[RedwoodPark]

This is encouraging news. Did you read the full report? Wonder what the timeline is for the future trials?

[Farooqji in reply to RedwoodPark]

Estimated Study Completion Date :May 1, 2019

clinicaltrials.gov/ct2/show...

[RedwoodPark in reply to Farooqji]

That's not too far out! 👍

[JANVAN]

Thanks Iqbaliqbal !!

Can you forward it to Simon (Science of Parkinson) ?

and how are you doing with Ibogaine ??'

and do you use B1 ??

[FMundo]

Announcement of Phase II Clinical Trial in July, 2017:

Prexton Therapeutics Initiates Phase 2 Trial of Foliglurax for Parkinson’s Patients

Prexton Therapeutics has initiated a new Phase 2 clinical trial to assess the safety and effectiveness of its investigational therapy Foliglurax (PXT002331) in Parkinson’s disease patients treated with levodopa, but who are experiencing end-of-dose wearing off and levodopa-induced dyskinesia (involuntary movements).

Levodopa is the most important first-line medication for the management of Parkinson’s, and often is administered in combination with carbidopa. However, long-term use of levodopa can cause a phenomenon called “wearing off,” “fading effect,” and “end-of-dose effect,” all of which describe the drug’s diminished effectiveness.

Levodopa-induced dyskinesia is a condition characterized by involuntary movements that usually occur after prolonged treatment with levodopa in Parkinson’s patients. The drug is part of the class of medications called central nervous system agents and acts by being converted into the neurotransmitter dopamine, which helps the brain regulate movement and emotional responses, among others.

Upon loss of the dopamine-producing neurons, Parkinson’s patients experience symptoms of tremor, slowness, stiffness, and balance problems. Treatments are focused on reducing these effects by replacing dopamine or using agents that mimic its effects. This approach, however, is not long-lasting, and drugs like levodopa, lose effectiveness as the disease progresses.

The investigational therapy Foliglurax activates a specific target of the glutamatergic system, mGluR4, which is emerging as a promising target for the treatment of motor (and non-motor) symptoms in Parkinson’s, via a non-dopaminergic strategy.

In a previous Phase 1 clinical trial, completed in September 2016, results showed that Foliglurax is safe and well-tolerated, with a favorable body distribution. This prompted the next phase for investigating the drug’s effects in Parkinson’s patients.

The AMBLED trial (NCT03162874) is a double-blind, randomized, placebo-controlled, parallel-arm Phase 2 study designed to enroll 165 patients across six European countries – the U.K., Germany, France, Austria, Spain, and Italy.

Participants will be randomized to receive one of two oral doses of Foliglurax (10 mg or 30 mg), or placebo, for a 28-day period, after which they will be assessed for the reduction levodopa-induced motor complications. Data from the trial is expected in 2019.

“The start of this Phase II trial is another significant milestone for Prexton and for Parkinson’s patients desperately in need of novel and innovative therapeutic solutions,” Francois Conquet, CEO, of Prexton Therapeutics, said in a press release. “We are excited about the potential of Foliglurax in addressing these needs.”