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Massimiliano Rossi

Publications and source records attributed to Massimiliano Rossi.

11 recordsLinked to original sources
PubMed2026

A Phase 3 Trial of Vosoritide in Children with Hypochondroplasia.

BACKGROUND: Hypochondroplasia, a fibroblast growth factor receptor 3 (FGFR3)-related skeletal condition characterized by disproportionate short stature and a spectrum of clinical features, has no available targeted therapies. Vosoritide, a C-type natriuretic peptide analogue approved for the treatment of achondroplasia, is being investigated for hypochondroplasia. METHODS: In this phase 3, multicenter trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen. The primary end point was change from baseline in annualized growth velocity at week 52 versus placebo. Confirmatory statistical testing using hierarchical procedures to control for type I error at the one-sided 0.025 significance level (equivalent to the two-sided 0.05 level) was performed for the primary and six key secondary efficacy end points. The safety and side effect profile of vosoritide versus placebo was assessed. RESULTS: A total of 81 participants were randomly assigned to receive vosoritide (n=41) or placebo (n=40). At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus -0.39 cm/year with placebo (LSM difference of 2.33 cm/year; 95% confidence interval, 1.85-2.82 cm/year; two-sided P<0.0001). Most participants in the vosoritide group (87.8%) and the placebo group (72.5%) experienced at least one adverse event (AE). There were no reports of grade 3 or higher AEs, AEs leading to treatment discontinuation, or deaths. CONCLUSIONS: One year of vosoritide treatment significantly increased linear growth in children with hypochondroplasia. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT06455059.).

Journal Article↗
PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗
PubMed2007

Pharmacological enhancement of mutated alpha-glucosidase activity in fibroblasts from patients with Pompe disease.

We investigated the use of pharmacological chaperones for the therapy of Pompe disease, a metabolic myopathy due to mutations of the gene encoding the lysosomal hydrolase alpha-glucosidase (GAA) and characterized by generalized glycogen storage in cardiac and skeletal muscle. We studied the effects of two imino sugars, deoxynojirimycin (DNJ) and N-butyldeoxynojirimycin (NB-DNJ), on residual GAA activity in fibroblasts from eight patients with different forms of Pompe disease (two classic infantile, two non-classic infantile onset, four late-onset forms), and with different mutations of the GAA gene. We demonstrated a significant increase of GAA activity (1.3-7.5-fold) after imino sugar treatment in fibroblasts from patients carrying the mutations L552P (three patients) and G549R (one patient). GAA enhancement was confirmed in HEK293T cells where the same mutations were overexpressed. No increase of GAA activity was observed for the other mutations. Western blot analysis showed that imino sugars increase the amount of mature GAA molecular forms. Immunofluorescence studies in HEK293T cells overexpressing the L552P mutation showed an improved trafficking of the mutant enzyme to lysosomes after imino sugar treatment. These results provide a rationale for an alternative treatment, other than enzyme replacement, to Pompe disease.

Adult↗
PubMed2005

A study of electronic structures of Pt3M (M=Ti,V,Cr,Fe,Co,Ni) polycrystalline alloys with valence-band photoemission spectroscopy.

The surface valence-band densities of states (DOS) of Pt(3)M (M=Ti,V,Cr,Fe,Co,Ni) polycrystalline alloys were investigated with ultraviolet photoemission spectroscopy. Upon annealing the ion-sputter-cleaned alloys at high temperatures, the observed valence-band DOS spectra clearly show the modified electronic structures on the surfaces suggesting the surface segregation of Pt as predicted in thermodynamic models. The measured d-band centers and widths for the annealed alloy surfaces show qualitatively the same trend as predicted by density-functional-theory calculations based on the model of a Pt "skin" on the topmost surface layer and a subsurface layer enriched in the 3d transition metal.

Journal Article↗
PubMed2005

Characterization of liver involvement in defects of cholesterol biosynthesis: long-term follow-up and review.

Inborn defects of cholesterol biosynthesis are a group of metabolic disorders presenting with mental retardation and multiple congenital anomalies (MCA/MR syndromes). Functional and structural liver involvement has been reported as a rare (2.5-6%) complication of the Smith-Lemli-Opitz syndrome (SLOS) and it has not been fully characterized. Here, we report on a long-term follow-up study of four patients with SLOS, and one case with lathosterolosis who presented with liver disease and underwent an extensive diagnostic work-up. Reports of liver involvement in cholesterol biosynthesis defects are reviewed. Two main different patterns of liver involvement emerged: progressive cholestasis, and stable isolated hypertransaminasemia. In our series, the first pattern was found in two patients with SLOS and one with lathosterolosis, and the second in two SLOS cases. Cholestasis was associated with early lethality and normal serum gamma-glutamyl-transferase (GGT) levels in SLOS, while possible prolonged survival and high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in both conditions. Liver biopsy performed in one of our SLOS patients with isolated hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes. The presence of liver involvement in 16% of the SLOS patients diagnosed at our Center suggests that this complication might have been underestimated in previously reported cases, possibly overshadowed by the severity of multiple malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia can occur also in other disorders of cholesterol biosynthesis, such as mevalonic aciduria, desmosterolosis, Conradi-Hunermann syndrome, Greenberg dysplasia, and Pelger-Huet homozygosity syndrome. This group of inherited disorders should be considered in the differential diagnosis of patients presenting with liver disease associated with developmental delay and/or multiple malformations. Periodic liver function evaluations are recommended in these patients.

Child↗
PubMed2003

The appearance of the feet in Pfeiffer syndrome caused by FGFR1 P252R mutation.

Patients affected by Pfeiffer syndrome generally present with syndromic craniosynostosis and typical limb defects including broad thumbs, wide halluces with varus deformity, toe syndactyly and sometimes elbow ankylosis. This autosomal dominant condition can be caused by mutations in either fibroblast growth factor receptor gene type 1 or 2 (FGFR1 or FGFR2). We report four new affected families showing an FGFR1 P252R mutation and emphasize the characteristic malformations of the feet in this form of Pfeiffer syndrome. In one family this was the only abnormality.

Acrocephalosyndactylia↗
PubMed2003

[Cardiac rehabilitation in a HIV-patient treated with protease inhibitors].

We report a case of a 38-years-old HIV-positive patient, undergoing in the last 18 months therapy with three antiretroviral drugs including a protease inhibitor (nelfinavir). The patient was admitted in our Department with acute anterior myocardial infarction and was submitted to PTCA on the left anterior descending coronary artery. The patient, a 30 cigarettes/day smoker, with family history of hypertension and high levels of trygliceride and cholesterol, was subsequently admitted to our Cardiac Rehabilitation Unit. Cardiac Rehabilitation Program was composed of cycle aerobic training 4 times/week, dietary education, psychologic support and therapy with pravastatin, aspirin, nitrate, enalapril, and carvedilol. At the end of the 8 week Rehabilitation Program we observed a normalization of cholesterol and trygliceride levels and an improvement of cardiac functional capacity and mental health.

Adult↗
PubMed2002

Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase.

We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.

Abnormalities, Multiple↗
PubMed2002

Unbalanced translocation (3;5)(q26.1;p14): a clinical report.

A patient with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome had an unbalanced translocation (3;5)(q26.1;p14), causing partial 5p monosomy and partial 3q trisomy. The phenotype observed in this patient results from the combination of those described in the isolated dup(3q) and del(5p) syndromes. Some clinical features of this patient are shared by the Smith-Lemli-Opitz syndrome (SLOS), a well-known MCA/MR syndrome due to the deficiency of 7-dehydrocholesterol reductase (DHCR7). We review the previously reported cases of chromosomal anomalies with clinical features suggesting SLOS.

Abnormalities, Multiple↗
PubMed2002

Effects of sample storage on 7- and 8-dehydrocholesterol levels analysed on whole blood spots by gas chromatography-mass spectrometry-selected ion monitoring.

Smith-Lemli-Opitz syndrome (SLOS) patients have increased 7- and 8-dehydrocholesterol (DHC) concentrations. Using gas chromatography-mass spectrometry with selected ion monitoring we investigated whether storage time (24 h, 7 and 30 days, and 22 months at room temperature or at 4 degrees C) affected DHC concentrations in whole blood spots (WBSs) from SLOS patients and normal controls. Our results suggest that WBS sterol analysis can be used for SLOS screening and possibly related inborn errors of sterol metabolism with a 100% sensitivity and specificity on specimens stored for up to 30 days, either at room temperature or 4 degrees C. After 22 months of storage at both temperature SLOS samples can be indistinguishable from control samples. Therefore, great caution should be used to exclude SLOS by sterol analysis of WBSs stored for a long time.

Cholestadienols↗