Protection Against Parkinson’s Disease Progression: Clinical Experience

Abstract

Summary:Treatments with potential neuroprotective capability for Parkinson's disease (PD) have been investigated in randomized, controlled, clinical trials and other studies since the mid-1980s. Although promising leads have arisen, no therapy has been proven to halt or slow disease progression. Several large-scale studies have highlighted progress in methodology, as well as the frustrations of translating laboratory science to practical applications. This review summarizes findings from clinical trials with several classes of compounds, including monoamine oxidase-B inhibitors (selegiline, lazabemide, rasagiline), dopaminergic drugs (ropinirole, pramipexole, levodopa), antioxidant strategies (␣-tocopherol), mitochondrial energy enhancers (coenzyme Q 10 , creatine), antiapoptotic agents (TCH346, minocycline, CEP-1347), and antiglutamatergic compounds (riluzole). Beyond small-molecule pharmacology, gene therapy approaches, such as delivering neurotrophic substances (e.g., neurturin) by viral vector, are the next generation of treatment options.

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

“…Clinical trials have evaluated several agents targeting oxidative damage in PD, including coenzyme Q10, α-tocopherol, selegiline, and rasagaline; but disappointingly none of these trials have demonstrated an unequivocal slowing of disease progression [9,10]. These negative results are difficult to interpret, however, because it is unknown whether the agents succeeded in having a significant effect on neuronal oxidative stress at the doses employed.…”

Neuroprotective effect of naphtha[1,2-d]thiazol-2-amine in an animal model of Parkinson's disease

“…benztrophine, orphenadrine). Although the introduction of levodopa therapy in particular revolutionized the management of PD, the immediate or delayed side effects this treatment can cause, the most invalidating being dyskinesia, have prompted the search for alternative pharmacological strategies that reduce the incidence of this neurodegenerative disease by protecting or regenerating dopaminergic neurons [10]. The progressive neurodegeneration in PD is not halt/slow down by the currently used drug therapies.…”

Capacities of the dopamine receptor agonist pramipexole in the treatment of patients with Parkinson’s disease

“…д. ), эти рабо-ты in vivo стали первым конкретным индикатором возможной нейропро-текции при использовании АДР [16,19]. Очевидно, что подтверждение та-кого эффекта требует дальнейших ис-следований с усовершенствованием их «протективного» дизайна и внедрени-ем в практику более информативных биомаркеров нейродегенерации.…”