Administration Of Human Growth Hormone Research Articles

Can Human Growth Hormone Accelerate Tendon and Ligament Injury Recovery?

Studies involving human fibroblasts and use of human growth hormone (HGH) administration for injury recovery are limited. It is plausible that if the administration of HGH to human cells increased cellular proliferation and differentiation, then HGH might be able to assist in accelerating recovery from injury. HGH will increase proliferation and differentiation of human tendon and ligament fibroblasts in vitro based on both a single-dose and a sustained-dose model of HGH administration. Basic science cellular study. Human tendon and ligament tissue were harvested from 24 patients. Tissue samples were digested with type I collagenase to isolate the target cell types. HGH was administered directly to isolated cells at doses ranging from 100 pg/mL to 10 µg/mL, either in a single-dose or a sustained-dose model. Proliferation was analyzed at days 4 and 7. Differentiation of ligament and tendon fibroblasts was assessed at day 14. Administration of a single-dose of HGH to both cell types demonstrated similar or inferior cellular proliferation compared with controls after 7 days. For the sustained-dosing model of ligament fibroblasts, only the 100 ng/mL concentration demonstrated at least statistically similar or improved proliferation compared with controls. When examining the 100 ng/mL HGH concentration with larger sample sizes, cellular proliferation was not improved over controls for any cell type for the single- or sustained-dosing models. Proliferation for tendon fibroblasts was either similar or inferior to the control group at all concentrations of HGH. There was no clear dose-response relationship demonstrating enhanced collagen production with administration of HGH to suggest it enhances injury recovery. HGH administered to human tendon and ligament fibroblasts does not appear to positively affect cellular proliferation and differentiation. This study does not support the use of HGH for accelerating recovery from injury.

Development of nano-liposomal human growth hormone as a topical formulation for preventing uvb-induced skin damage

Due to its involvement in skin maintenance and repair, topical administration of recombinant human growth hormone (rhGH) is an interesting strategy for therapeutic purposes. We have formulated and characterized a topical rhGH-loaded liposomal formulation (rhGH-Lip) and evaluated its safety, biological activity, and preventive role against UVB-induced skin damage. The rhGH-Lip had an average size and zeta potential of 63 nm and −33 mV, respectively, with 70 % encapsulation efficiency. The formulation was stable at 4 °C for at least one year. The SDS-PAGE and circular dichroism results showed no structural alterations in rhGH upon encapsulation. In vitro, studies in HaCaT, HFFF-2, and Ba/F3-rhGHR cell lines confirmed the safety and biological activity of rhGH-Lip. Franz diffusion cell study showed increased rhGH skin permeation compared to free rhGH. Animal studies in nude mice showed that liposomal rhGH prevented UVB-induced epidermal hyperplasia, angiogenesis, wrinkle formation, and collagen loss, as well as improving skin moisture. The results of this study show that rhGH-Lip is a stable, safe, and effective skin delivery system and has potential as an anti-wrinkle formulation for topical application. This study also provides a new method for the topical delivery of proteins and merits further investigation.

The Effect of Human Growth Hormone Treatment on the Development of Slipped Capital Femoral Epiphysis: A Cohort Analysis With 6 Years of Follow-up.

Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescents that can result in substantial complications, impacting the quality of life. Human Growth Hormone (HGH) administration may elevate the risk of SCFE, though the relationship remains unclear. Clarifying this association could enable better monitoring and earlier diagnosis of SCFE in patients receiving HGH. The aim of the study is to investigate the association between HGH administration and the incidence of SCFE. This retrospective cohort study utilized data from the TriNetX research database from January 2003 to December 2022. The study included 2 cohorts: an HGH cohort including 36,791 patients aged below 18 years receiving HGH therapy and a control group consisting of patients who did not receive HGH therapy. A 1:1 propensity score matching technique was employed to ensure comparability between the HGH and no-HGH cohorts. The primary outcome measure was the development of SCFE identified by International Classification of Diseases codes. For comparative analysis, both risk ratios (RR) and hazard ratios were computed to evaluate the association between HGH therapy and the development of SCFE. The HGH cohort had an increased risk of SCFE compared with the no-HGH cohort (RR: 3.5, 95% CI: 2.073, 5.909, P <0.001) and had an increased hazard of developing SCFE (hazard ratio: 2.627, 95% CI: 1.555, 4.437, P <0.001). Patients with higher exposure to HGH (defined as >10 prescriptions) had an RR of 1.914 (95% CI: 1.160, 3.159, P =0.010) when compared with their counterparts with ≤10 prescriptions. In the largest study to date, HGH administration was associated with an elevated risk of SCFE in children in a dose-dependent manner. Level III-therapeutic retrospective cohort study.

Silica-collagen nanoformulations with extended human growth hormone release

Growth hormone deficiency has been treated by the daily administration of recombinant human growth hormone (hGH) for decades. Patient compliance to this treatment is generally incomplete due to challenges including dose frequency and lack of perceived benefits. This stimulates the research on new formulations to reduce the number of periodic administrations. In this study silica nanoparticles and silica-collagen nanocomposites were evaluated for hGH loading and release. Bare nanoparticles showed higher hGH adsorption capacity than thiol- and isobutyl-bearing particles of similar diameters. Monitoring of bound protein conformation changes indicated hGH structure retention when adsorbed on bare silica nanoparticles and suggested no alterations on protein activity. Protein-loaded particles incorporated into collagen matrices (silica-collagen nanocomposites) showed a progressive protein release profile different from the observed for hGH-loaded silica nanoparticles and hGH-loaded collagen matrices. While both the collagen and the silica nanoparticle systems reached a 100 % release after 4 and 7 days respectively, silica-collagen nanocomposites showed a bi-phasic prolonged hGH release reaching approximately an 80 % after 15 days. These findings suggest that biocompatible silica-collagen nanocomposites could be used as vehicles for the prolonged delivery of hGH which could lead to a potential reduction in the number of periodic administrations.

Magnetically actuating implantable pump for the on-demand and needle-free administration of human growth hormone

A bolus of human growth hormone (hGH) is often prescribed for the treatment of growth hormone deficiency, which requires frequent injections in current clinical settings. This painful needle-involved delivery often results in poor patient compliance, leading to low medication adherence and poor clinical outcomes. Therefore, we propose a magnetically actuating implantable pump (MAP) that can infuse an accurate dose of hGH only at the time of non-invasive magnet application from the skin. The MAP herein could reproducibly infuse 20.6 ± 0.9 μg hGH per actuation without any leak at times without actuation. The infused amount increased proportionally with an increase in the number of actuations. When the MAP was implanted and actuated with a magnet in animals with growth hormone deficiency for 21 days, the profiles of plasma hGH concentration and insulin-like growth factor (IGF)-1, as well as changes in body weight, were similar to those observed in animals treated with conventional subcutaneous hGH injections. Therefore, we anticipate that the MAP fabricated in this study can be a non-invasive alternative to administer hGH without repeated and frequent needle injections.

A high-throughput assay for the quantification of intact Insulin-like Growth Factor I in human serum using online SPE-LC-HRMS

Quantification of IGF-I is relevant in both doping control as a biomarker of growth hormone (GH) misuse in sports, and in the clinical field for longitudinal follow-up of patients with disorders related to the GH axis. Currently, better standardization of IGF-I measurements using mass spectrometry is in our best interest as it would enable long-term monitoring of an athletes’ IGF-I levels by its addition to the Athlete Biological Passport (ABP).Here, a simplified and rapid top-down LC-HRMS method for quantification of IGF-I in human serum is presented. A ten-minute precipitation-based offline sample preparation is combined with online sample clean-up and separation on a conventional LC, resulting in a total runtime of nine minutes in between injections. The method was validated in the relevant range of 50–1000 ng/mL for the following parameters: linearity, precision, bias, Limit Of Quantification (LOQ), carry-over, selectivity, recovery and ion suppression. As proof of concept, the presented LC-HRMS assay was compared with results from a previous inter-laboratory study on intact IGF-I quantification using four human GH administration samples. It was additionally compared with the IDS-iSYS immunoassay using 47 athlete serum samples, showing good overall agreement with a slight positive bias of 24.2 ng/mL for the LC-HRMS assay at a mean sample concentration of 234 ng/mL. Also, a discrepancy between commercially available IGF-I reference material for the calibration of quantitative assays is discussed. This is of importance if LC-MS assays for IGF-I are to be harmonized.

Inter-Laboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured Intact by Mass Spectrometry

Insulin-like growth factor-I (IGF-1) is measured mainly by immunoassay for the diagnosis and treatment of growth hormone (GH) disorders, and to detect misuse of GH in sport. Immunoassays often have insufficient inter-laboratory agreement, especially between commercial kits. Over the expected range of IGF-1 in blood (∼50-500 ng/mL), in an inter-laboratory study we previously established a measurement imprecision of 11% (%CV) for the digested protein analyzed by LC-MS. Measuring intact IGF-1 by LC-MS should be simpler. However, no inter-laboratory agreement has been published. Intact and trypsin-digested IGF-1 in 32 serum samples from healthy volunteers and human growth hormone administration studies were analyzed by LC-MS using different instruments in five laboratories, as well as by immunoassay in a single laboratory. Another 100 samples were analyzed for IGF-1, both intact and after trypsin-digestion, in each laboratory by LC-MS. The statistical relationship between measurements and the imprecision of each assay group was assessed. An intra-laboratory variability of 2-4% CV was obtained. Inter-laboratory variability was greater at 14.5% CV. Orthogonal regression of intact versus trypsin-digestion methods (n = 646) gave a slope of 1.01 and intercept of 2.05 ng/mL. LC-MS measurements of IGF-1 by intact and trypsin-digestion methods are not statistically different and each is similar to immunoassay. The two LC-MS approaches may be used interchangeably or together to eliminate concerns regarding an immunoassay IGF-1 measurement. Because intact and digested IGF-1 measurements generally agreed within 20% of each other, we propose this as a criterion of assay acceptability.

Achieving Optimal Short- and Long-term Responses to Paediatric Growth Hormone Therapy

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Effects of recombinant human growth hormone administration on cardiovascular risk factors in obese children with relative growth hormone deficiency

BackgroundBased on the sample of obese children with relative growth hormone deficiency (GHD), the objective of our study was to determine the effects of rhGH treatment on cardiovascular risk factors, including body mass index (BMI), lipid levels and glucose metabolism index.MethodsA total of 43 obese children with relative GHD were included in our final analysis. The obese subjects were divided into two groups: recombinant human growth hormone (rhGH) treatment group and untreated control group.ResultsAfter 6 months, subjects in the rhGH treatment group had significant reductions in BMI standard deviation scores (SDS) compared with controls (2.32 ± 0.85 vs. 2.80 ± 0.61; P = 0.041), and Insulin-like growth factor 1(IGF-1) level increased during rhGH treatment, in comparison with the control group (702.91 ± 246.03 vs. 348.30 ± 131.93 ng/mL, P < 0.001). GH treatment reduced low density lipoprotein cholesterol (LDL-C) (2.20 ± 0.45 vs. 2.63 ± 0.76 mmol/L, P = 0.027), aspartate aminotransferase (AST) (21.26 ± 5.72 vs. 32.30 ± 17.68 mmol/L, P = 0.006) as well as alanine aminotransferase (ALT) (16.70 ± 6.72 vs. 45.20 ± 46.62 mmol/L, P = 0.002), and increased high density lipoprotein cholesterol (HDL-C) (1.45 ± 0.40 vs. 1.19 ± 0.23 mmol/L, P = 0.016) levels compared with the control group.ConclusionRhGH treatment for 6 months on obese children with relative GHD reduces BMI SDS, stabilize IGF-1 levels, and exerts beneficial effects on blood lipid profiles and live enzyme compared with untreated control group. Moreover, GH administration has no significant effects on increased insulin resistance and no adversely effect on glucose homeostasis.

Plasma biomarker proteins for detection of human growth hormone administration in athletes

Human growth hormone (GH) is a naturally occurring hormone secreted by the pituitary gland with anabolic and growth-promoting activities. Since an increased availability of recombinant GH (rGH) for the treatment of GH-deficient patients, GH has been abused in sports and it is prohibited. “GH-isoform” and “biomarkers” tests are currently available for detection of GH abuse in sports, however both methods suffer from shortcomings. Here, we report on a proteomic approach to search for novel protein biomarkers associated with rGH administration in non-elite athletes. In this study, participants received either placebo or rGH for 8 weeks, and were followed over a 6-week washout period. We used 2-D DIGE and iTRAQ LC-MS/MS analyses to expose rGH-dependent marker proteins. Eight rGH-dependent plasma proteins namely apolipoproptein-L1, alpha-HS-glycoprotein, vitamin D-binding protein, afamin, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-ALS, lumican and extracellular matrix proteins 1 were identified. Apolipoprotein L1 and alpha-HS-glycoprotein were validated by Western blots to confirm their identities and expression patterns in rGH- and placebo-treated subject cohorts. Independent confirmation of these putative GH-responsive biomarkers would be of value for clinical practices and may have sports anti-doping utility.

2nd year efficacy results of once-weekly administration of CTP-modified human growth hormone (MOD-4023): a phase 2 study in children with growth hormone deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Safety and tolerability of once-weekly administration of CTP-modified human growth hormone (MOD-4023): phase 2 study in children with growth hormone deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats.

Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-α, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population.

A Child with Local Lipohypertrophy following Recombinant Human Growth Hormone Administration.

Local lipohypertrophy due to recombinant human growth hormone (rhGH) administration is a rare phenomenon. Here, we report a case of an 11-year-old girl who presented with a paraumbilical swelling, approximately one year after the start of rhGH treatment for short stature due to the presumed diagnosis of partial growth hormone insensitivity. Ultrasound imaging revealed an asymmetric distribution of subcutaneous fat tissue at the rhGH administration site, indicating local lipohypertrophy. After sparing her routine injection site and alternating other sites, the swelling disappeared within 6 months. Although the precise cause of local lipohypertrophy resulting from rhGH administration is still unclear, it might be related to the presumed diagnosis of partial growth hormone insensitivity.

Self-administration of Recombinant Human Growth Hormone with an Electronic Device: Clinical, Economic and Management Benefits of Objective Adherence Monitoring

Purpose: The aim was to identify factors affecting treatment adherence and to assess the clinical, economic and management impact of growth hormone deficiency treatment using an electronic auto-injector for recombinant human growth hormone (r-hGH) administration in children. Patients and Methods: A literature review was conducted in PubMed up to 31JUL2013, including the following search terms: “growth hormone deficiency”, “human-recombinant growth hormone” and “treatment adherence”. An economic model was developed to estimate the economic benefits of using an electronic injection device. In order to quantify this benefit, potential savings due to growth hormone cartridge optimization were analyzed. Results: From the literature review, the following key factors were found to affect treatment adherence: type of device used, discomfort, complexity of treatment regimens, long-term treatment, age and patient or family understanding of treatment benefits were assessed. A better adjustment to prescribed daily dose (accuracy up to 0.01 mg) with the electronic device results in a better optimization of vials and could save an average of 5% of total treatment costs in terms of doses not wasted, amounting to €245 of potential savings per patient and year of treatment. Conclusion: The use of an electronic device for r-hGH administration and monitoring may provide a better identification of responder and adherent patients. It may also generate savings in annual r-hGH consumption by hospitals and regional healthcare services.

178. Early Treatment for Growth Hormone Deficiency Based on Naked DNA Administration in Dwarf Mice Allows Efficient Catch-Up Growth

Growth hormone deficiency (GHD) is the major disease of the pituitary gland and is characterized by significant changes in body composition, bone density, lipid metabolism amongst others. Current treatment consists of daily administration of recombinant human growth hormone. As an alternative, our group investigates a gene therapy strategy for GHD based on the administration of a plasmid encoding the human growth hormone gene (hGH) under the control of ubiquitin C promoter, followed by electrotransfer. In order to get the maximize phenotype correction and to compare treatment of pubertal relative to adult mice, a bioassay was performed using 40 or 80 days old lit/scid mice, respectively. The mice were injected with 50mg of plasmid DNA in each side of non-exposed tibialis cranialis muscle, followed by electrotransfer at high and low voltage pulses.At day 30, the treated groups showed a significant body weight variation of 3.64g/mice/day for pubertal mice, 2.07g/mice/day for the adult mice, and -0.01g/mice/day for the control group. View Large Image | Download PowerPoint SlideAfter 40 days, a second round of DNA administration was carried out, and as no significant body weight gain in the following days was observed, the assay was terminated at day 60. Remarkably, the parameters directly related to linear growth (table 1table 1), like increases in nose-to-tail, tail and femur lengths, were 1.2 – 2.0 fold higher for pubertal mice as compared to the adult group, and treatment of pubertal mice resulted in a striking catch-up growth of 36 to 77%.Table 1Parameters directly related to longitudinal growth after 60 days of hGH-DNA administration in 40 days or 80 days old mice lit/scid micenIncrease %Catch-up (%)Nose-to-tail length (cm)saline – 40 days411.6hGH-DNA – 40 days322.235.6untreated scid – 40 days49.0saline – 80 days42.9hGH-DNA – 80 days311.725.7untreated scid – 80 days511.2Tail lenght (cm)saline – 40 days413.1hGH-DNA – 40 days324.239.0untreated scid – 40 days45.8saline – 80 days41.0hGH-DNA – 80 days312.023.6untreated scid – 80 days511.3Femur lenght (mm)hGH-DNA – 40 days318.71177.5hGH-DNA – 80 days416.11139.91Calculated with basis on saline-treated co-aged miceMoreover mIGF-I, the main GH-dependent mediator of growth, was measured in plasma samples and the levels of mIGF-I in treated pubertal lit/scid mice were completely normalized 15 days post treatment and not significantly different to values for co-aged untreated non-dwarf mice, however the same did not occur to the adult lit/scid treated mice and their co-aged scid mice. These results are very promising and demonstrates the significance of early onset of gene therapy treatment in the lit/scid mouse model for phenotypic correction of GHD.

A Case of Functional Growth Hormone Deficiency and Early Growth Retardation in a Child With IFT172 Mutations

Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

Effects of recombinant human growth hormone (rhGH) administration on body composition and cardiovascular risk factors in obese adolescent girls.

BackgroundObesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study’s purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance.Methods22 obese girls 13–21 years old were followed for a randomized 6-month trial of rhGH vs. placebo/no treatment. At baseline and 6-months, DXA was performed for body composition, MRI to measure visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT), and fasting blood drawn for IGF-1, inflammatory cardiovascular risk markers [soluble intercellular adhesion molecule (sICAM), high sensitivity CRP], lipids and HbA1C. An oral glucose tolerance test (OGTT) was performed. Twelve girls completed the 6-month visit. Baseline and mean 6-month change were compared between the groups using the Student t-test and the relationship between variables was determined through multiple regression analysis.ResultsAfter 6-months, the rhGH group maintained IGF-1 levels, and had decreases in total cholesterol (p = 0.03), sICAM-1 (p = 0.04) and HbA1C (p = 0.03) compared to placebo/no treatment. The rhGH group trended towards greater decreases in LDL and 2-hour OGTT glucose. Glucose tolerance did not worsen with rhGH administration.ConclusionsAdministering rhGH in small doses is able to stabilize IGF-1 levels in obesity. We have also shown that rhGH administration leads to an improvement in some markers of cardiovacular risk with without adversely affecting glucose tolerance.Trial registrationClinical Trial Registration Number: NCT01169103.

Human Growth Hormone Increases SMN Expression and Survival in Severe Spinal Muscular Atrophy Mouse Model

Autosomal recessive spinal muscle atrophy (SMA) is characterized by the loss of α motor neurons resulting in progressive muscle loss and respiratory failure. SMA is one of the most common inherited causes of infant death with a carrier frequency of 1 in 50 and a calculated prevalence of about 1 in 11,000 live births in the US. The low amount of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes SMA. A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from the paralog SMN2 gene compensating in part for the absence of the SMN1 gene. Our group has previously shown that activation of the STAT5 pathway by lactation hormone prolactin (PRL) increased SMN levels, improved motor function and enhanced survival in a severe SMA mouse model. Given that human growth hormone (HGH) is also known to activate the STAT5 signalling pathway and is already used extensively in clinical settings, we thus elected to assess its impact on SMN levels. Administration of HGH in NT2 cells activated STAT5 pathway which resulted into significant induction in SMN protein levels. Furthermore, systemic administration of HGH to transgenic SMA mice induced SMN protein levels in the brain and spinal cord samples. Critically, HGH treatment improved disease phenotype and increased survival in two severe SMA mouse models. Our results confirm earlier work suggesting STAT5 pathway activators as potential therapeutic compounds for the treatment of SMA and identify HGH as one such promising agent.

Product wastage from modern human growth hormone administration devices: a laboratory and computer simulation analysis

BackgroundTreatment of growth hormone disorders typically involves daily injections of human growth hormone (GH) over many years, incurring substantial costs. We assessed the extent of undesired GH loss due to leakage in the course of pen preparation prior to injection, and differences between the prescribed dose, based on patient weight, and the actual delivered dose based on pen dosing increments in five GH administration devices.MethodsNorditropin® prefilled FlexPro®, NordiFlex®, NordiLet®, and durable NordiPen®/SimpleXx® 5 mg pens (Novo Nordisk A/S, Bagsværd, Denmark) and durable Omnitrope® Pen-5 devices (Sandoz, Holzkirchen, Germany) were tested (n = 40 for each device type). Product wastage was measured in accordance with validated protocols in an ISO (International Organization for Standardization) 11608-1 and Good Manufacturing Practice compliant laboratory. The average mass of wasted GH from each device type was measured in simulations of dripping with the needle attached prior to injection and while setting a dose. Statistical significance (P < 0.05) was confirmed by Student’s t-test, and a model was constructed to estimate mean annual GH wastage per patient in cohorts of pediatric patients with GH disorders.ResultsMean GH mass wasted with the needle on prior to injection was 0.0 μg with Norditropin pens, relative to 98 μg with Omnitrope Pen-5. During dose dialing, 0.0–2.3 μg of GH was lost with Norditropin pens versus 0.8 μg with Omnitrope Pen-5. All Norditropin and Omnitrope device comparisons were statistically significant. Modeling GH wastage in a US cohort showed 5.5 mg of annual GH wastage per patient with FlexPro versus 43.6 mg with Omnitrope, corresponding to 7–8 additional pens per patient annually.ConclusionOverall, Norditropin pens resulted in significantly less wastage than the Omnitrope Pen-5. The study suggests that GH devices of the same nominal volume exhibit differences that may affect the frequency of GH prescription refills required to remain adherent to therapy.