Old wines in new bottles: Repurposing opportunities for Parkinson's disease

Kakkar, Ashish Kumar; Singh, Harmanjit; Medhi, Bikash

doi:10.1016/j.ejphar.2018.04.023

Cited by 16 publications

(14 citation statements)

References 144 publications

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“…Repurposing is by no means a new idea in medicine, indeed, many venerable and well-established drugs, for example, the beta-blocker propranolol, have been extensively repurposed many times in the past. However, as an explicit development strategy, repurposing is being increasingly pursued in a number of different disease areas [2–4]. Indeed, data from PubMed show that the number of publications related to drug repurposing or repositioning has increased exponentially since 2004 [5].…”

Section: Introductionmentioning

confidence: 99%

ReDO_DB: the repurposing drugs in oncology database

Pantziarka¹,

Verbaanderd²,

Sukhatme³

et al. 2018

ecancer

103

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Repurposing is a drug development strategy that seeks to use existing medications for new indications. In oncology, there is an increased level of activity looking at the use of non-cancer drugs as possible cancer treatments. The Repurposing Drugs in Oncology (ReDO) project has used a literature-based approach to identify licensed non-cancer drugs with published evidence of anticancer activity. Data from 268 drugs have been included in a database (ReDO_DB) developed by the ReDO project. Summary results are outlined and an assessment of clinical trial activity also described. The database has been made available as an online open-access resource (http://www.redo-project.org/db/).

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Section: Introductionmentioning

confidence: 99%

ReDO_DB: the repurposing drugs in oncology database

Pantziarka¹,

Verbaanderd²,

Sukhatme³

et al. 2018

ecancer

103

View full text Add to dashboard Cite

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“…Current treatments for PD are only symptomatic and have no effects on the ongoing neurodegeneration [ 22 ]. The ideal therapeutic treatment for PD should have both symptomatic and restorative effects aimed at preserving midbrain DA neurons from degeneration [ 23 , 24 ]. In this sense, adult neural stem cells grafting into animal experimental models of neurodegenerative diseases have shown beneficial effects promoting both trophic and anti-inflammatory actions [ 25 – 31 ].…”

Section: Introductionmentioning

confidence: 99%

Counteracting neuroinflammation in experimental Parkinson’s disease favors recovery of function: effects of Er-NPCs administration

Carelli

Giallongo

Gombalová

et al. 2018

J Neuroinflammation

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BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disease, presenting with midbrain dopaminergic neurons degeneration. A number of studies suggest that microglial activation may have a role in PD. It has emerged that inflammation-derived oxidative stress and cytokine-dependent toxicity may contribute to nigrostriatal pathway degeneration and exacerbate the progression of the disease in patients with idiopathic PD. Cell therapies have long been considered a feasible regenerative approach to compensate for the loss of specific cell populations such as the one that occurs in PD. We recently demonstrated that erythropoietin-releasing neural precursors cells (Er-NPCs) administered to MPTP-intoxicated animals survive after transplantation in the recipient’s damaged brain, differentiate, and rescue degenerating striatal dopaminergic neurons. Here, we aimed to investigate the potential anti-inflammatory actions of Er-NPCs infused in an MPTP experimental model of PD.MethodsThe degeneration of dopaminergic neurons was caused by MPTP administration in C57BL/6 male mice. 2.5 × 105 GFP-labeled Er-NPCs were administered by stereotaxic injection unilaterally in the left striatum. Functional recovery was assessed by two independent behavioral tests. Neuroinflammation was investigated measuring the mRNAs levels of pro-inflammatory and anti-inflammatory cytokines, and immunohistochemistry studies were performed to evaluate markers of inflammation and the potential rescue of tyrosine hydroxylase (TH) projections in the striatum of recipient mice.ResultsEr-NPC administration promoted a rapid anti-inflammatory effect that was already evident 24 h after transplant with a decrease of pro-inflammatory and increase of anti-inflammatory cytokines mRNA expression levels. This effect was maintained until the end of the observational period, 2 weeks post-transplant. Here, we show that Er-NPCs transplant reduces macrophage infiltration, directly counteracting the M1-like pro-inflammatory response of murine-activated microglia, which corresponds to the decrease of CD68 and CD86 markers, and induces M2-like pro-regeneration traits, as indicated by the increase of CD206 and IL-10 expression. Moreover, we also show that this activity is mediated by Er-NPCs-derived erythropoietin (EPO) since the co-injection of cells with anti-EPO antibodies neutralizes the anti-inflammatory effect of the Er-NPCs treatment.ConclusionThis study shows the anti-inflammatory actions exerted by Er-NPCs, and we suggest that these cells may represent good candidates for cellular therapy to counteract neuroinflammation in neurodegenerative disorders.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1375-2) contains supplementary material, which is available to authorized users.

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“…Nilotinib is a selective breakpoint cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitor developed for CML patients who are resistant to treatment with imatinib [1, 2]. Nilotinib is more potent and selective than imatinib, has improved brain penetration, and is considered one of the most effective drugs for treatment of CML today [2].…”

Section: Discussionmentioning

confidence: 99%

“…Nilotinib is a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia (CML) by deactivating the Philadelphia chromosome, which contains the fusion gene BCR-ABL . The BCR-ABL gene is also present in patients with Parkinson disease (PD) [1]. Over-activation of tyrosine kinase may indicate increased oxidative stress, which may play a role in the loss of dopaminergic neurons contributing to the pathogenesis of PD.…”

Section: Introductionmentioning

confidence: 99%

Nilotinib-Induced Dystonia and Cognitive Deficits in a Neurologically Normal Patient with Chronic Myeloid Leukemia

Chan

Shah

Moguel‐Cobos

2019

Case Reports in Neurological Medicine

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Nilotinib is a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia (CML). This agent is also being studied in neurodegenerative disorders including Parkinson disease. Studies have shown that nilotinib may decrease the accumulation of parkin substrates and decrease the loss of dopaminergic cells. The use of nilotinib in neurologic disorders is relatively new, and little information about this use has been published. We report on a patient receiving nilotinib for CML. The patient had no previous neurologic deficits, and developed intermittent dystonic posturing of the left upper extremity and cognitive impairment after she began nilotinib treatment. The mechanisms behind this adverse effect are not clear; however, her symptoms began after nilotinib was introduced, decreased with dose reduction, stopped with its cessation, and re-emerged when the medication was restarted. To our knowledge, this is the first reported patient with neurologic symptoms secondary to nilotinib use.

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Old wines in new bottles: Repurposing opportunities for Parkinson's disease

Cited by 16 publications

References 144 publications

ReDO_DB: the repurposing drugs in oncology database

ReDO_DB: the repurposing drugs in oncology database

Counteracting neuroinflammation in experimental Parkinson’s disease favors recovery of function: effects of Er-NPCs administration

Nilotinib-Induced Dystonia and Cognitive Deficits in a Neurologically Normal Patient with Chronic Myeloid Leukemia

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