Review: Neuroprotective, Multimodal Treatment Needed Against Parkinson Disease

Treatment strategies focused on dopaminergic regeneration rather than symptomatic relief may transform the way Parkinson disease is managed.

The use and development of neuroprotective and multimodal treatment methods against Parkinson disease (PD) could cause a shift in the paradigm of treatment for the condition, according to a review published in Neural Regeneration Research.

Current pharmacological treatment for PD focuses on providing symptomatic relief and improving functional capacity through practices of dopamine replacement, like through the administration of levodopa. Although these methods prove to be effective early on, responsiveness wanes over time and often leads to adverse effects such as dyskinesias, motor fluctuations, and behavior changes.

Review authors suggest that pharmacological treatment focusing on the counteraction of dopaminergic neuronal death as opposed to treatment adhering to the “one-disease-one-target” viewpoint may change the way PD is managed. As of currently, no regenerative, neuroprotective, or disease-modifying therapeutic strategy has been approved as a PD therapy.

Recent research focusing on stem cell secretome (SCS) and the secretome of mesenchymal stem cells (MSCs) has explored their therapeutic potential for central nervous system (CNS) neurodegenerative diseases such as PD. When examined in vitro, MSCs secretome has demonstrated positive effects in neuronal and glial survival and differentiation and axonal growth. Secretome from MSCs extracted from bone marrow has also been shown to improve motor control and rescue of dopaminergic neurons in a rat preclinical model of PD.

Similarly, research has demonstrated that the sole injection of neural progenitor cells (NPCs) secretome in a 6-OHDA rat model of PD can promote dopaminergic neuronal survival and improve animal motor deficits.

N-Acetylcysteine (NAC) has also been proven to have positive effects on nervous system regeneration. In recent clinical trials, intravenous administration of NAC led to an increase in blood redox rations of glutathione and may lead to positive dopaminergic effects in patients with PD. NAC has also been shown to increase brain synaptic and nonsynaptic connections, diminish oxidative damage considered to be a driver of PD progression, raise brain synaptic mitochondrial complex I activity and anti-inflammatory protection, and prevent reactive oxygen species accumulation.

Combining SCS with neuroprotective drugs that can mitigate oxidative stress, excitotoxicity, inflammation, and dopamine would yield the most positive effects against PD given the complex nature of the condition. The combination of NAC neuroprotective/disease-modifying properties with SCS regenerative properties may transform the current approach to PD treatment.

A combinatorial strategy may help overcome limitations of single drug approaches, as well as help clinicians manage patients’ symptomatology by lengthening the period of response to medication with enhanced tolerance and modifying the progression of PD, the review authors noted.

Future preclinical studies are needed to understand the combinatorial nature of the proposed SCS-NAC therapeutic strategy, and routes of administration, dosage regimens, extent of therapies, monitoring plans, and randomized procedures should be considered.

Reference

Silva RC, Domingues HS, Salgado AJ, Teixeira FG. From regenerative strategies to pharmacological approaches: can we fine-tune treatment for Parkinson's disease? Neural Regen Res. 2022;17(5):933-936. doi:10.4103/1673-5374.324827