BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment.
RESULTS: Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event.
CONCLUSIONS: Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy. Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691.

Organomegaly can be a strong predictor of an underlying pathological condition. There are many standard tables available in various texts listing the normal organ weight range, yet there is a lack of a standard table that is accepted globally. The main reason behind this is variation in organ weight due to socioeconomic status, geographical variation, and racial and stature variation among different global populations. The Western population has different stature compared to our population, that is, residents of Uttarakhand, India. Different studies tabulated organ weights in different regions of the world and correlated with different bodily parameters such as sex, race, stature, BMI, etc, which have shown a significant variation. There are different sets of data available that cannot be accepted universally due to regional variation. Most of the studies done in various parts of the world do not specify the condition of the organ, whether it was normal at the time of study or not. The methods of dissection of organs were also not explained in different studies. In this study, a total of eight organs were weighed from 137 autopsies conducted at the mortuary of the All India Institute of Medical Sciences Rishikesh over a period of 1.5 years. It was found that the average brain weighed in males was 1313.2 gm (±127.7 gm) and among females, it was 1218.0 gm (±122.82 gm). The weight of the heart was 310.1 gm (±83.97 gm) in males and 241.2 gm (±71.42 gm) in females. Right and left lungs weighed 499.4 gm (±207.5 gm)/407.5 gm (±128.66 gm) and 459.6 gm (±179.19 gm)/369.4 gm (±144.17 gm) among males and females, respectively. The liver weight was 1477.0 gm (±370.52 gm) in males and 1309.0 gm (±274.18 gm) among females. Spleen weighed 154.0 gm (±74.63 gm) in males and 156.0 gm (±65.0 gm) in females. The right and left kidneys weighed 125.9 gm (±37.92 gm)/108.1 gm (±28.80 gm) and 126.3 gm (±31.26 gm)/106.6 gm (±22.4 gm) among males and females, respectively. In our study, we have done a histological examination to rule out any pathological condition before including the weight of the organs in the study. The present study is to derive a standard organ weight among the inhabitants of Uttarakhand, India, and to look for a variation in organ weight among different studies done in the past in different regions of the world.

This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults.
A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics.
Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event-related discontinuations. Most adverse events were mild.
Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD.

Schistosoma mansoni is highly endemic in Tanzania and affects all age groups at different degrees. However, its control approach does not include adult individuals who are equally at risk and infected. To justify the inclusion of adult individuals in MDA programs in Tanzania, the present study focused on determining the prevalence of S. mansoni infection and its related morbidities among adult individuals. This was a cross sectional study conducted among 412 adult individuals aged 18-89 years living in selected villages of Rorya and Butiama districts located along the shoreline of the Lake Victoria. A pretested questionnaire was used to collect socio-demographic and socio-economic information of participants. Ultrasonographic examinations were conducted for all study participants using the Niamey protocol. A single stool sample was obtained from all study participants and examined for S. mansoni using the Kato-Katz technique. The study revealed a high prevalence of S. mansoni (56.3%), and the majority of infected individuals had a light intensity of infection. Ultrasonographic findings revealed that 22.4% of adult individuals had periportal fibrosis (PPF) (grade C-F), with 18.4% having grade C and D and 4% having grade E and F. Males had the highest prevalence of PPF (31.7% vs 10.8%, P<0.001). Organomegaly was common with 28.5% and 29.6% having splenomegaly and hepatomegaly, respectively. S. mansoni infection and its related morbidities included PPF, hepatomegaly, and splenomegaly were common among adult individuals. To reduce the level of transmission of S. mansoni infection, planned mass drug administration campaigns should include adult individuals living in these villages.