Evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, therefore the recent clinical trial warranted exploration of trying to attenuate pathogenic microglial function. They sought to test the safety and efficacy of NLY01—a brain penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation—in Parkinson's disease.
An investigation brain penetrant, pegylated analogue of the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) known as NLY01 did not lead to improvement in Parkinson's disease symptoms compared with placebo.
Neither 2.5 mg or 5.0 mg of weekly NLY01 injections showed any difference from placebo in the sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III scores at 36 weeks, according to Andrew McGarry, MD, of Rowan University in Camden, New Jersey, and colleagues.
McGarry and co-authors randomized 255 people with early untreated Parkinson's disease to subcutaneous 2.5 mg or 5.0 mg NLY01, or placebo (85 people in each group). Participants were told to administer the drug or placebo once a week for 36 weeks. Mean age was 61.5 and more than half of participants were men.
The primary efficacy endpoint was change from baseline to week 36 in the sum of MDS-UPDRS parts II and III scores. Part II assesses motor aspects of experiences of daily living and part III is a motor examination. Each MDS-UPDRS sub-scale has a rating from 0 (normal) to 4 (severe).
Secondary endpoints included MDS-UPDRS part I scores (non-motor aspects of experiences of daily living), clinical and patient impressions of severity, cognitive test scores, and dopamine transporter imaging parameters. No secondary endpoint differed from placebo at either dose.
NLY101 was generally safe and well tolerated. Gastrointestinal disorders emerged in 61% of the 2.5-mg dose group and 75% of the 5.0-mg group, most frequently nausea.
Participants under age 60 showed nominally significant reductions from baseline in the sum of MDS-UPDRS parts II and III scores at 36 weeks compared with placebo, "a finding that could be driven in part by a greater decline in the younger placebo group," McGarry and colleagues acknowledged. "Further studies should look to test a younger population for potentially better treatment outcomes."
The phase II trial may have been too short to see effects clearly, the researchers noted. Exenatide-PD3, a phase III, 2-year study of exenatide in 200 people with mild-to-moderate Parkinson's disease on standard treatment, is underway; results are expected in 2024.
thelancet.com/journals/lane...
Best Wishes to all with your health and into the New Year,
Merry Christmas.