We are Fundraising for maxwell tk2 nucleosides treatment
Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency
Maxwell has TK2 mitochondrial disease so is unable to breathe by himself. He’s connected to a ventilator 24/7, he can’t talk, walk or move his arms and legs this means he requires around the clock care by his parents and nursing team. There is a treatment available for Maxwell which unfortunately isn’t funded. We have been in contact with Hospital and have had a meet and greet already on the 3rd of February 2016 The treatment costs £17,770.00 per year.
Maxwell will be the first person in the UK to go onto this treatment.
We as parents will try anything to help Maxwell have a better quality of life and be happy.
Deoxypyrimidine monophosphates pathways.
Graphical summary of the pathways modulated by oral gavage dCMP/dTMP treatment.
A dTMP metabolism. dTMP treatment may enter as monophosphate into the mitochondria bypassing the TK2 enzymatic defect as demonstrated by the increased level of dTTP in postnatal day 13 mutant mouse tissues. However, dTMP is also rapidly degraded by 50-nucleotidase in the small intestine to the nucleoside (dT), which may be processed via three different pathways: (i) phosphorylated by residual Tk2 activity to eventually produce dTTP within mitochondria; (ii) converted to dTMP by cytosolic Tk1; or (iii) catabolized by thymidine phosphorylase (TP). The combination of reduced Tk1 activity in brain and increased thymidine phosphorylase (TP) activity in small intestine after postnatal day 13 may account for the reduced efficacy of the treatment in rescuing the dNTP pool balance after age 13 days.
B dCMP metabolism. dCMP/dTMP treatment did not increase dCTP levels in mitochondria of Tk2!/! mice suggesting that dCMP administered orally does not enter into mitochondria. Instead, dCMP degraded to nucleoside (dC) may be a source of dTMP as shown in the figure or may be catabolized to uracil by cytosolic TP.