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Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient

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ABSTRACT

We have recently published on the limited effectiveness of sirolimus as a treatment option for hypoglycaemia as a consequence of hyperinsulinism. Our data oppose the view that mTOR inhibitors provide new opportunities for the treatment of patients with hyperinsulinism. We are not convinced by the argument that any benefit for some patients outweighs the potential and later long-term problems that accompany mTOR inhibition in the neonate. We also express the opinion that caution must be taken when repurposing/repositioning therapies in the field of rare disease.

No MeSH data available.


Relative expression of mTOR in CHI tissue. The relative expression of mTOR mRNA is no different in focal (n = 5 cases, ‘Lesion’) or diffuse CHI (n = 3 cases, ‘Diffuse’) when compared to age-matched controls (n = 4 cases)
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Fig1: Relative expression of mTOR in CHI tissue. The relative expression of mTOR mRNA is no different in focal (n = 5 cases, ‘Lesion’) or diffuse CHI (n = 3 cases, ‘Diffuse’) when compared to age-matched controls (n = 4 cases)

Mentions: To address concerns about the widening use of Sirolimus in these difficult to treat patients, the experiences of two international specialist treatment Centres for CHI have been published. Szymanowski et al. (2016) report in a cohort of 10 patients, that the effectiveness of Sirolimus is far worse than that of either diazoxide or Octreotide, and that Sirolimus carries a greater risk of side-effects and short-term complications than either of the standard medications for CHI [10]. There was no evidence to support the proposed mechanisms of action of Sirolimus on β-cells. The expression of the mTOR gene was no different in control and CHI tissue (Fig. 1), and moreover the mTOR pathway is not implicated in the network of pathways causally-linked to disease. The authors of Szymanowski et al. (2016) also noted that one patient treated in the cohort stopped sirolimus after one year as drug efficacy was lost.Fig. 1


Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient
Relative expression of mTOR in CHI tissue. The relative expression of mTOR mRNA is no different in focal (n = 5 cases, ‘Lesion’) or diffuse CHI (n = 3 cases, ‘Diffuse’) when compared to age-matched controls (n = 4 cases)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5391606&req=5

Fig1: Relative expression of mTOR in CHI tissue. The relative expression of mTOR mRNA is no different in focal (n = 5 cases, ‘Lesion’) or diffuse CHI (n = 3 cases, ‘Diffuse’) when compared to age-matched controls (n = 4 cases)
Mentions: To address concerns about the widening use of Sirolimus in these difficult to treat patients, the experiences of two international specialist treatment Centres for CHI have been published. Szymanowski et al. (2016) report in a cohort of 10 patients, that the effectiveness of Sirolimus is far worse than that of either diazoxide or Octreotide, and that Sirolimus carries a greater risk of side-effects and short-term complications than either of the standard medications for CHI [10]. There was no evidence to support the proposed mechanisms of action of Sirolimus on β-cells. The expression of the mTOR gene was no different in control and CHI tissue (Fig. 1), and moreover the mTOR pathway is not implicated in the network of pathways causally-linked to disease. The authors of Szymanowski et al. (2016) also noted that one patient treated in the cohort stopped sirolimus after one year as drug efficacy was lost.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

We have recently published on the limited effectiveness of sirolimus as a treatment option for hypoglycaemia as a consequence of hyperinsulinism. Our data oppose the view that mTOR inhibitors provide new opportunities for the treatment of patients with hyperinsulinism. We are not convinced by the argument that any benefit for some patients outweighs the potential and later long-term problems that accompany mTOR inhibition in the neonate. We also express the opinion that caution must be taken when repurposing/repositioning therapies in the field of rare disease.

No MeSH data available.