Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials

Author(s):  
Rosanna Tortelli ◽  
Davide Seripa ◽  
Francesco Panza ◽  
Vincenzo Solfrizzi ◽  
Giancarlo Logroscino
2021 ◽  
Vol 14 (3) ◽  
pp. 281
Author(s):  
Francesco Oddone ◽  
Luca Rossetti ◽  
Mariacristina Parravano ◽  
Diego Sbardella ◽  
Massimo Coletta ◽  
...  

Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).


Author(s):  
Jeffrey L. Cummings ◽  
Jagan A. Pillai

Neurodegenerative diseases (NDDs) are growing in frequency and represent a major threat to public health. Advances in scientific progress have made it clear that NDDs share many underlying processes, including shared intracellular mechanisms such as protein misfolding and aggregation, cell-to-cell prion-like spread, growth factor signaling abnormalities, RNA and DNA disturbances, glial cell changes, and neuronal loss. Transmitter deficits are shared across many types of disorders. Means of studying NDDs with human iPS cells and transgenic models are similar. The progression of NDDs through asymptomatic, prodromal, and manifest stages is shared across disorders. Clinical features of NDDs, including cognitive impairment, disease progression, age-related effects, terminal stages, neuropsychiatric manifestations, and functional disorders and disability, have many common elements. Clinical trials, biomarkers, brain imaging, and regulatory aspects of NDD can share information across NDDs. Disease-modifying and transmitter-based therapeutic interventions, clinical trials, and regulatory approaches to treatments for NDDs are also similar.


2015 ◽  
Vol 37 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Wei Zhang ◽  
Xue-yan Chen ◽  
Su-wen Su ◽  
Qing-zhong Jia ◽  
Tao Ding ◽  
...  

2008 ◽  
Vol 17 (10-11) ◽  
pp. 1103-1113 ◽  
Author(s):  
Yvan Torrente ◽  
Elio Polli

Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. The lack of effective treatment and the characteristic of their pathology make these diseases appropriate candidates for cell therapy. Mesenchymal stem cells (MSCs) are multipotent stem-like cells that are capable of differentiating into mesenchymal and nonmesenchymal lineages. Their regenerative capacity after in vivo transplantation into animal models of neurodegenerative diseases has suggested that they could be useful against human diseases. Human bone marrow-derived MSCs (hMSCs) can be easily amplified in vitro and their transdifferentiation has been claimed in vitro and in vivo in neural cells. There are some doubts concerning the exact mechanisms responsible for the beneficial outcome observed after MSC transplantation into neurodegenerating tissues. Possible interpretations include cell replacement, trophic factor delivery, and immunomodulation. This review mainly concerns hMSCs transplantation in neurodegenerative diseases, because it has proven to be feasible, safe, and potentially effective. Although they have been used in hundreds of clinical trials, mixed results and no functional and long-lasting integration have so far been observed. hMSCs transplantations therefore still have their “dark side.” However, the challenge in well-planned clinical trials merits discussion.


2017 ◽  
Vol 88 (Suppl 1) ◽  
pp. A77.3-A77
Author(s):  
James D Stefaniak ◽  
Thomas CH Lam ◽  
Naomi E Sim ◽  
Rustam Al-Shahi Salman ◽  
David P Breen

2012 ◽  
Vol 11 (7) ◽  
pp. 643-650 ◽  
Author(s):  
Wendy R Galpern ◽  
Jacqueline Corrigan-Curay ◽  
Anthony E Lang ◽  
Jeffrey Kahn ◽  
Danilo Tagle ◽  
...  

Author(s):  
Artur Pałasz ◽  
Marek Krzystanek

AbstractMolecules that selectively act on N-methyl-D-aspartate (NMDA) receptors may have a multidirectional effect by modulating the activity of NMDARs, affecting their active sites as well as by changing the composition of their subunits. The results of the clinical trials conducted so far in mood disorders and schizophrenia indicate that such agents may become new effective drugs for the treatment of these diseases. Number of spider neurotoxins e.g. ctenitoxins extracted from Phoneutria sp. venom act as potent and selective NMDAR blockers that do not disturb cortical and hippocampal glutamate signaling, LTP generation and synaptic neurochemistry. Possibly this intriguing kind of promising neuroregulatory peptides and polyamines can be clinically applicable in a wide spectrum of neuropsychiatric disorders, including epilepsy, neurotrauma and ischemic injuries. These novel medications can potentially be helpful in the future treatment of stroke and several neurodegenerative diseases.


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