I came across a few links in reading about this topic so I thought I would share them here in one place.
Also visit the index of all of the SRPT research on BiotechDueDiligence.
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[S34.004] Forty-Eight Week Follow-Up Data from a Phase I/IIa Extension Study of PRO051/GSK2402968 in Subjects with Duchenne Muscular Dystrophy
Nathalie Goemans, Leuven, Belgium, Mar Tulinius, Gothenburg, Sweden, Rosamund Wilson, Marlborough, Wiltshire, United Kingdom, Judith van Deutekom, Sjef de Kimpe, Giles Campion, Leiden, The Netherlands
OBJECTIVE: To evaluate the efficacy and safety of 48 weeks of treatment with PRO051/GSK2402968 in boys with Duchenne muscular dystrophy (DMD).BACKGROUND: DMD patients suffer from progressive muscle degeneration due to mutations in the DMD gene and resulting absence of functional dystrophin in the muscle cell wall. PRO051/GSK2402968 is an antisense oligonucleotide compound which induces exon 51 skipping during pre-mRNA splicing and produces novel dystrophin expression in a subpopulation of DMD patients. DESIGN/METHODS: Twelve DMD patients with mutations correctable by skipping exon 51, (11 ambulatory, 1 non-ambulatory at study entry) completed a dose-escalation Phase I/IIa study (Netherlands Trial Register #NTR124) and entered the open-label extension study. Subjects were to receive weekly subcutaneous injections of 6mg/kg of PRO051/GSK2402968 in the extension study, regardless of earlier dose. All subjects were at stable steroid doses during the study. Assessments were performed at baseline and 4-week intervals thereafter. RESULTS:All boys reported treatment-emergent AEs. The most common AEs were increased urinary 1-microglobulin (100%), proteinuria (92%) and injection site reactions (100%). However, the majority of AEs were considered to be mild; there were no severe treatment-related AEs. There was some evidence of mild proteinuria, confirmed as greater than the upper limit of normal range (>0.15g<0.3g/24hrs), in four boys at subsequent 24-hr collection. Increases in some renal and hepatic parameters were observed but none were considered progressive. Four serious AEs (not related to treatment) were reported. There was an improvement in 6-minute walking distance test (6MWD) from 12 weeks; this was maintained until week 48, when the mean (SD) improvement in 6MWD was +29 (80)m. CONCLUSIONS: PRO051/GSK2402968 6mg/kg administered weekly by subcutaneous injection was generally well tolerated across 48 weeks of treatment. Renal and hepatic function warrant further monitoring. As 6MWD is expected to deteriorate over 48 weeks, the improvements observed in this functional measurement are encouraging.
Wetzels JF, Gerlag PG, Sluiter HE, Hoitsma AJ, Koene RA.
We studied the effect of prednisone on urinary protein excretion in 19 patients with a nephrotic syndrome, who were treated with prednisone (125-150 mg) on alternate days. We found a typical, fluctuating pattern of proteinuria resulting from an increased protein excretion rate on prednisone days and a decreased protein excretion rate on nonprednisone days. The urinary protein excretion on prednisone days was 9.9 +/- 3.3 g/24 h, as compared to 5.7 +/- 3.8 g/24 h on nonprednisone days (mean +/- SD). In the whole group of patients the percentual change in proteinuria was significantly correlated with the endogenous creatinine clearance. However, systematic differences between creatinine excretion rates on prednisone and nonprednisone days were not found in individual patients. In 6 patients, renal hemodynamics were studied more precisely, using a single injection technique. Only a slight and nonsignificant decrease in glomerular filtration rate was found on nonprednisone days (delta = -9.6 +/- 16.3%; mean +/- SD). Filtration fraction remained unchanged. It is therefore suggested that the effects of prednisone on proteinuria are not simply mediated by overall changes in renal hemodynamics.
Proteinuria detection in children is a challenge. Five percent to 15% and 0.4-1% of school children present either transient (benign) or persistent increased amount of protein in urine, respectively. Persistent proteinuria constitutes not only a sign of overt kidney disease but may also be the first indicator of silent renal damage. Proteinuria is a marker for hyperfiltration in individuals with reduced nephron mass and one of the most important independent risk factor for renal disease progression as well. It constitutes the single most important risk factor for future loss of kidney function, preceding glomerular filtration rate reduction. Further, proteinuria itself is diagnostic of cardiovascular disease with prognostic value and target organ involvement in high-risk populations such as diabetic, obese, hypertensive children, or those with known reduced renal mass or previous renal injury. Current strategies to prevent CKD progression, a concept known as renoprotection, are focused on reducing urinary protein excretion among other factors. Reversibility of organ damage in early stages is possible; therefore, pediatricians should screen children for proteinuria or microalbuminuria, mainly in high-risk groups.
Proteinuria in Children (AAFP)
Pediatric Proteinuria (Medscape)
PROTEINURIA AND OTHER MARKERS OF CHRONIC KIDNEY DISEASE:
A POSITION STATEMENT OF THE NATIONAL KIDNEY FOUNDATION (NKF)
AND THE NATIONAL INSTITUTE OF DIABETES DIGESTIVE AND KIDNEY