Real-life impacts of olipudase alfa: The experience of patients and families taking an enzyme replacement therapy for acid sphingomyelinase deficiency.

BACKGROUND: Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers. METHODS: Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach. RESULTS: Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived. CONCLUSIONS: These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD.

Visceral symptoms in patients with anterior cutaneous nerve entrapment syndrome (ACNES): expression of viscerosomatic reflexes?

PURPOSE: Anterior cutaneous nerve entrapment (ACNES) is characterized by neuropathic pain in a predictable, circumscript abdominal area. The diagnostic delay is long, with half of ACNES-affected individuals reporting nausea, bloating, or loss of appetite mimicking visceral disease. The aim of this study was to describe these phenomena and to determine whether treatment could successfully reverse the visceral symptoms. METHODS: This prospective observational study was conducted between July 2017 and December 2020 at SolviMáx, Center of Excellence for Chronic Abdominal Wall and Groin Pain, Máxima Medical Center, Eindhoven. Adult patients who fulfilled published criteria for ACNES and reported at least one visceral symptom at intake were eligible for the study. A self-developed Visceral Complaints ACNES Score (VICAS) questionnaire that scores several visceral symptoms (minimum 1 point, maximum 9 points) was completed before and after therapy. The success of treatment was defined as at least 50% reduction in pain. RESULTS: Data from 100 selected patients (86 females) aged 39 ± 5 years were available for analysis. Frequently reported symptoms were abdominal bloating (78%), nausea (66%) and altered defecation (50%). Successful treatment significantly reduced the number of visceral symptoms, with a VICAS before of 3 (range 1-8) and after of 1 (range 0-6) (p < 0.001). A low baseline VICAS was associated with successful treatment outcome (OR 0.738, 95% CI 0.546-0.999). CONCLUSION: Patients with ACNES may report a variety of visceral symptoms. Successful treatment substantially reduces these visceral symptoms in selected patients.

Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia.

AIMS: To elucidate the role of cerebral serotonin neurotransmission in visceral perception in functional dyspepsia (FD), we observationally examined the regional expression level of the serotonin transporter (SERT) and its correlation with clinical symptoms. MAIN METHODS: FD patients (Rome III criteria; N=9, age range: 36-76years) and healthy controls (N=8, age range: 25-61years) participated in this study. Positron emission tomography scanning with [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB), which binds specifically to SERT, was used to quantify the binding potential (BPND) of [(11)C]DASB in the midbrain, thalamus, caudate, putamen, amygdala, and hippocampus with reference to co-registered magnetic resonance images. Clinical symptoms were assessed using the Gastrointestinal Symptoms Rating Scale (GSRS). Self-Rating Depression Scale (SDS), and State-Trait Anxiety Inventory (STAI). KEY FINDINGS: BPND of the midbrain (P=0.041) and thalamus (P=0.031) was higher in FD patients than in controls. The BPND values in the midbrain correlated with total GSRS (r=0.663, P=0.004) and abdominal pain (r=0.419, P=0.047) scores. Its values in the thalamus correlated with total GSRS (r=0.423, P=0.044), abdominal pain (r=0.502, P=0.022), and indigestion (r=0.476, P=0.028) scores. Its value in the hippocampus correlated with abdominal pain and state-STAI scores (r=0.528, P=0.017; r=0.428, P=0.043). SIGNIFICANCE: Up-regulation of the SERT level in the midbrain and thalamus may underlie the pathogenesis of FD such as abdominal and psychological symptoms via a brain-gut interaction.