Exenatide had positive effects on practically defined off-medication motor scores in Parkinson’s disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.
We recently demonstrated that NLY01, a novel glucagon-like peptide-1 receptor agonist, exerts neuroprotective effects in two mouse models of PD in a glia-dependent manner. NLY01 prevented microglia from releasing inflammatory mediators known to convert astrocytes into a neurotoxic A1 reactive subtyp …
A study published on the JAMA Network focused on the long-term effect of initiating pramipexole vs levodopa in early PD. The subjects were followed for up to two years and after six years. Disability was assessed using the modified Shwab and England Activities of Daily Living Scale. Other factors that were assessed included daytime sleepiness; disease severity; dopaminergic events; edema; depression; cognitive impairment and quality of life. Self-reported results were similar. Dopaminergic motor complications were more common in the initial levodopa group (68.4%) although disabling dyskinesias were uncommon in both groups. The mean (SD) Epworth Sleepiness Scale score was significantly higher in the initial pramipexole group. Mean (SD) changes from baseline in the total Unified Parkinson’s Disease Rating Scale score did not significantly differ. The study concluded that persistent differences favoring initial pramipexole were seen in the rates of dopaminergic motor complications, with less severe somnolence favoring initial levodopa.
A 2003 study published on Springer.com looked at pramipexole in comparison with I-dopa. The study subjects were twenty right-handed patients with early or mild PD. They were evaluated using neuropsychological and clinical assessments during three treatment modalities. 1. When in the off treatment condition; 2. When on pramipexole and 3. When on i-dopa. In comparison to the off treatment condition, the DA-agonist pramipexole produced a significant impairment of short term verbal memory, attentional-executive functions, and verbal fluency, while l-dopa did not. Pramipexole opposite to l-dopa, failed to improve FAS and Stroop tests. Pramipexole may worsen cognitive functions although not exceeding normative values.
A 2018 Springer article examines drug repurposing in PD due to the ever-increasing costs and lengthy processes for drug development. Existing compounds are being approved for other indications as novel treatments in PD. Advances in rational and systemic drug repurposing have identified a number of drugs with potential benefits for PD pathology and offer a potentially quicker route to drug discovery. Among the drugs being considered for repurposing for PD are ambroxol; isradipine; Inosine; ursodeoxycholic acid; deferiprone; exenatide; Nilotinib and Simvastatin. Despite the potential advantages offered by drug repurposing, as a strategy, it offers unique challenges, including the unavoidable need for expensive and risky clinical trials to demonstrate safety and efficacy in a new population while the limited patent protection often means a lack of commercial interest or incentive for further investment.
Dr. Stephen Mullin of the University of Plymouth talks for The Cure Parkinson’s Trust about the research into GBA Parkinson’s and the current convergent studies which all seem to be pointing towards GBA. In terms of the prospects to develop drugs to slow the development of PD, GBA is the most advanced. The next phase will be identifying PD patients who are carriers of the mutations in the GBA gene and beginning clinical human trials. Simultaneously there needs to be research into how GBA causes PD in humans. The prospects for ambroxol as a disease modifying agent in GBA PD are strong. Ambroxol has already been used by many patients and may be able to reverse some of the effects that lead to PD.
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