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Timing of therapies for Down syndrome: the sooner, the better.

Stagni F, Giacomini A, Guidi S, Ciani E, Bartesaghi R - Front Behav Neurosci (2015)

Bottom Line: Importantly, recent studies clearly show that treatment during the prenatal period can rescue overall brain development and behavior and that this effect outlasts treatment cessation.Indeed, treatment at adult life stages improves or even rescues hippocampal neurogenesis and connectivity and hippocampal-dependent learning and memory, although the duration of these effects still remains, in the majority of cases, a matter of investigation.For this reason we deem it extremely important to expedite the discovery of additional therapies practicable in humans in order to identify the best treatment/s in terms of efficacy and paucity of side effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna Bologna, Italy.

ABSTRACT
Intellectual disability (ID) is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Accumulating evidence shows that DS is characterized by numerous neurodevelopmental alterations among which the reduction of neurogenesis, dendritic hypotrophy and connectivity alterations appear to play a particularly prominent role. Although the mechanisms whereby gene triplication impairs brain development in DS have not been fully clarified, it is theoretically possible to correct trisomy-dependent defects with targeted pharmacotherapies. This review summarizes what we know about the effects of pharmacotherapies during different life stages in mouse models of DS. Since brain alterations in DS start to be present prenatally, the prenatal period represents an optimum window of opportunity for therapeutic interventions. Importantly, recent studies clearly show that treatment during the prenatal period can rescue overall brain development and behavior and that this effect outlasts treatment cessation. Although late therapies are unlikely to exert drastic changes in the brain, they may have an impact on the hippocampus, a brain region where neurogenesis continues throughout life. Indeed, treatment at adult life stages improves or even rescues hippocampal neurogenesis and connectivity and hippocampal-dependent learning and memory, although the duration of these effects still remains, in the majority of cases, a matter of investigation. The exciting discovery that trisomy-linked brain abnormalities can be prevented with early interventions gives us reason to believe that treatments during pregnancy may rescue brain development in fetuses with DS. For this reason we deem it extremely important to expedite the discovery of additional therapies practicable in humans in order to identify the best treatment/s in terms of efficacy and paucity of side effects. Prompt achievement of this goal is the big challenge for the scientific community of researchers interested in DS.

No MeSH data available.


Related in: MedlinePlus

Number of studies focused on pharmacotherapies in Down syndrome mouse models in the period 2002–2015. (A) Number or studies per year. (B) Cumulative number of studies in the period 2002–2008 and 2009–2015.
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Figure 1: Number of studies focused on pharmacotherapies in Down syndrome mouse models in the period 2002–2015. (A) Number or studies per year. (B) Cumulative number of studies in the period 2002–2008 and 2009–2015.

Mentions: During the past 14 years the number of studies focusing on pharmacotherapies for DS has grown almost exponentially. The results of a Medline research [a group of keywords was: “Down syndrome AND mouse model AND (therapy OR treatment OR restoration OR rescue OR improvement)”; a second group of keywords was: “Down syndrome AND mouse model AND LTP”] are summarized in Figure 1. Figure 1A summarizes the number of articles published since 2002 up to the beginning of current year. While in the period 2002–2008 the overall number of articles was 15 (Figure 1B), with a mean number of two articles per year, in the period 2009–2015 the overall number of articles was 40 (Figure 1B), with a mean number of six articles per year. These figures are quite encouraging because they show that the relatively small community of researchers interested in DS is making increasing efforts to find treatment for DS. This gives us hope that this intense commitment will produce good results in a near future.


Timing of therapies for Down syndrome: the sooner, the better.

Stagni F, Giacomini A, Guidi S, Ciani E, Bartesaghi R - Front Behav Neurosci (2015)

Number of studies focused on pharmacotherapies in Down syndrome mouse models in the period 2002–2015. (A) Number or studies per year. (B) Cumulative number of studies in the period 2002–2008 and 2009–2015.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594009&req=5

Figure 1: Number of studies focused on pharmacotherapies in Down syndrome mouse models in the period 2002–2015. (A) Number or studies per year. (B) Cumulative number of studies in the period 2002–2008 and 2009–2015.
Mentions: During the past 14 years the number of studies focusing on pharmacotherapies for DS has grown almost exponentially. The results of a Medline research [a group of keywords was: “Down syndrome AND mouse model AND (therapy OR treatment OR restoration OR rescue OR improvement)”; a second group of keywords was: “Down syndrome AND mouse model AND LTP”] are summarized in Figure 1. Figure 1A summarizes the number of articles published since 2002 up to the beginning of current year. While in the period 2002–2008 the overall number of articles was 15 (Figure 1B), with a mean number of two articles per year, in the period 2009–2015 the overall number of articles was 40 (Figure 1B), with a mean number of six articles per year. These figures are quite encouraging because they show that the relatively small community of researchers interested in DS is making increasing efforts to find treatment for DS. This gives us hope that this intense commitment will produce good results in a near future.

Bottom Line: Importantly, recent studies clearly show that treatment during the prenatal period can rescue overall brain development and behavior and that this effect outlasts treatment cessation.Indeed, treatment at adult life stages improves or even rescues hippocampal neurogenesis and connectivity and hippocampal-dependent learning and memory, although the duration of these effects still remains, in the majority of cases, a matter of investigation.For this reason we deem it extremely important to expedite the discovery of additional therapies practicable in humans in order to identify the best treatment/s in terms of efficacy and paucity of side effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna Bologna, Italy.

ABSTRACT
Intellectual disability (ID) is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Accumulating evidence shows that DS is characterized by numerous neurodevelopmental alterations among which the reduction of neurogenesis, dendritic hypotrophy and connectivity alterations appear to play a particularly prominent role. Although the mechanisms whereby gene triplication impairs brain development in DS have not been fully clarified, it is theoretically possible to correct trisomy-dependent defects with targeted pharmacotherapies. This review summarizes what we know about the effects of pharmacotherapies during different life stages in mouse models of DS. Since brain alterations in DS start to be present prenatally, the prenatal period represents an optimum window of opportunity for therapeutic interventions. Importantly, recent studies clearly show that treatment during the prenatal period can rescue overall brain development and behavior and that this effect outlasts treatment cessation. Although late therapies are unlikely to exert drastic changes in the brain, they may have an impact on the hippocampus, a brain region where neurogenesis continues throughout life. Indeed, treatment at adult life stages improves or even rescues hippocampal neurogenesis and connectivity and hippocampal-dependent learning and memory, although the duration of these effects still remains, in the majority of cases, a matter of investigation. The exciting discovery that trisomy-linked brain abnormalities can be prevented with early interventions gives us reason to believe that treatments during pregnancy may rescue brain development in fetuses with DS. For this reason we deem it extremely important to expedite the discovery of additional therapies practicable in humans in order to identify the best treatment/s in terms of efficacy and paucity of side effects. Prompt achievement of this goal is the big challenge for the scientific community of researchers interested in DS.

No MeSH data available.


Related in: MedlinePlus