Dodecyl Creatine Ester-Loaded Nanoemulsion as a Promising Therapy for Creatine Transporter Deficiency

Ullio-Gamboa, Gabriela; Udobi, Kenea C.; Dézard, Sophie; Perna, Marla K.; Miles, Keila N.; Costa, Narciso; Taran, Frédéric; Pruvost, Alain; Benoit, Jean‐Pierre; Skelton, Matthew R.; Lonlay, Pascale de; Mabondzo, Aloı̈se

doi:10.2217/nnm-2019-0059

Cited by 28 publications

(26 citation statements)

References 28 publications

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“…Here, we performed a randomized, blinded, placebo-controlled, preclinical study to explore the therapeutic efficacy of a chronic (24 week) oral daily treatment with cyclocreatine (cCr) at three different dose levels in CrT knock-out (CrT −/y ) mice. It has been reported that lipophilic analogs and other derivatives of Cr can enter cells independently of CrT and could represent a promising approach for CTD treatment 10 , 16 – 19 . In particular, cCr is a nearly planar Cr analog that can be phospho/dephosphorylated by Cr kinase, thus mimicking the metabolic function of Cr 10 , 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Cacciante

Gennaro

Sagona

et al. 2020

Sci Rep

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Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.

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Section: Introductionmentioning

confidence: 99%

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Cacciante

Gennaro

Sagona

et al. 2020

Sci Rep

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“…Liquid chromatography tandem mass chromatography LC-MS/MS technic was used to determine PDD005 concentration in the media from the in vitro study and in both plasma and brain homogenates from the in vivo study as we described previously 15,42 . Mobile phase A was H 2 O + 0.1% HCOOH and mobile phase B was ACN + 0.1% HCOOH.…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

A Small Compound Targeting Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau Pathology Treatment

Guyot

Leuxe

Disdier

et al. 2020

Sci Rep

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Neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are characterized by increased protein aggregation in the brain, progressive neuronal loss, increased inflammation, and neurogenesis impairment. We analyzed the effects of a new purine derivative drug, PDD005, in attenuating mechanisms involved in the pathogenesis of neurodegenerative diseases, using both in vivo and in vitro models. We show that PDD005 is distributed to the brain and can rescue cognitive deficits associated with aging in mice. Treatment with PDD005 prevents impairment of neurogenesis by increasing sex-determining region Y-box 2, nestin, and also enhances synaptic function through upregulation of synaptophysin and postsynaptic density protein 95. PDD005 treatment also reduced neuro-inflammation by decreasing interleukin-1β expression, activation of astrocytes, and microglia. We identified prohibitin as a potential target in mediating the therapeutic effects of PDD005 for the treatment of cognitive deficit in aging mice. Additionally, in the current study, glycogen synthase kinase appears to attenuate tau pathology. Based on current statistics, disorders of the central nervous system (CNS) will become a significant healthcare issue in the 21st century. Neurodegenerative disorders (NDs) can have a substantial impact on the quality of life for patients, often associated with progressive debilitation. Alzheimer's disease and Parkinson's disease are the most common forms of NDs for which the principal risk factor is age 1. Current therapeutic strategies often treat only the symptoms of the disease and can have problematic side effects in some patients. NDs are characterized by aggregation and accumulation of cellular proteins 2. For instance, in Alzheimer's disease, cellular metabolism dysfunction in the CNS results in the accumulation of amyloid β (Aβ) peptides (Aβ-42 and Aβ-40) and hyperphosphorylation of tau protein, which are associated with selective loss of neurons in the brain 3. Abnormal protein aggregation in the brain is also associated with inflammation 4 and impaired neurogenesis 5. A recent study

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“…In 2019, a study from Ullio-Gamboa et al addressed this challenge by synthesizing dodecyl creatine ester (DCE)-loaded nanoemulsion (with a size of 138–149 nm) [ 86 ]. This optimized formulation comprised 63% w / w Transcutol ® HP and 25% w / w of water, with an oil concentration which was maintained at 12% w / w , as well as DHA and Maisine ® CC (2:1% w / w ).…”

Section: Cns Disorders and Nanotherapeuticsmentioning

confidence: 99%

Think Big, Start Small: How Nanomedicine Could Alleviate the Burden of Rare CNS Diseases

Faouzi

Roullin

2021

Pharmaceuticals

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The complexity and organization of the central nervous system (CNS) is widely modulated by the presence of the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB), which both act as biochemical, dynamic obstacles impeding any type of undesirable exogenous exchanges. The disruption of these barriers is usually associated with the development of neuropathologies which can be the consequence of genetic disorders, local antigenic invasions, or autoimmune diseases. These disorders can take the shape of rare CNS-related diseases (other than Alzheimer’s and Parkinson’s) which a exhibit relatively low or moderate prevalence and could be part of a potential line of treatments from current nanotargeted therapies. Indeed, one of the most promising therapeutical alternatives in that field comes from the development of nanotechnologies which can be divided between drug delivery systems and diagnostic tools. Unfortunately, the number of studies dedicated to treating these rare diseases using nanotherapeutics is limited, which is mostly due to a lack of interest from industrial pharmaceutical companies. In the present review, we will provide an overview of some of these rare CNS diseases, discuss the physiopathology of these disorders, shed light on how nanotherapies could be of interest as a credible line of treatment, and finally address the major issues which can hinder the development of efficient therapies in that area.

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Dodecyl Creatine Ester-Loaded Nanoemulsion as a Promising Therapy for Creatine Transporter Deficiency

Cited by 28 publications

References 28 publications

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

A Small Compound Targeting Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau Pathology Treatment

Think Big, Start Small: How Nanomedicine Could Alleviate the Burden of Rare CNS Diseases

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