tbuckley/cabot-search huggingface dataset:
3-year posttreatment follow-up of radium-223 dichloride (Ra-223) safety in patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases from the phase 3 ALSYMPCA study.
Authors: Chris Parker, Nicholas J. Vogelzang, A. Oliver Sartor, Robert E. Coleman, Irene Skjorestad, Fang Fang, Sten Nilsson
Journal: Journal of Clinical Oncology (2015)

e16102 Background: Ra-223, an alpha-emitting radiopharmaceutical, significantly improved overall survival and was well tolerated in ALSYMPCA (Parker, NEJM2013). Ra-223 long-term safety monitoring is essential to a complete safety profile. Here we report adverse events (AEs) from ALSYMPCA pts 3 y after last pt’s first injection (inj). Methods: All pts were to enter designated follow-up from 4 wk after each pt’s last inj to 3 y after first inj. Only treatment (tx)-related AEs and specific diseases (acute myelogenous leukemia [AML], myelodysplastic syndrome [MDS], aplastic anemia [AA], primary bone cancer, primary cancer in other organs) were reported. Results: Of 921 pts (Ra-223, n = 614; pbo, n = 307), 575 entered follow-up (Ra-223, n = 407; pbo, n = 168). 336/407 (83%) Ra-223 pts and 119/168 (71%) pbo pts had 6 inj. Median follow-up time was 10.3 mo for Ra-223 pts and 7.6 mo for pbo pts. In the safety population, 27/405 (7%) Ra-223 pts and 8/167 (5%) pbo pts had 42 tx-related AEs (Table). Myelosuppression incidence was ≤ 3%. No pts had AML, MDS, or primary bone cancer; 1 Ra-223 pt had AA, and 3 Ra-223 and 3 pbo pts had primary cancer in other organs (Table). Conclusions: Long-term follow-up 3 y after last pt’s first inj showed no new safety concerns or secondary malignancies related to Ra-223. Clinical trial information: NCT00699751. AEs, n (%) Ra-223 n = 405* Pbo n = 167* All Gr Gr 3/4 All Gr Gr 3/4 Hematologic Anemia 11 (3) 5 (1) 5 (3) 1 (1) Aplastic anemia 1 (< 1) 1 (< 1) 0 0 Leukopenia 2 (< 1) 2 (< 1) 0 0 Neutropenia 2 (< 1) 2 (< 1) 0 0 Thrombocytopenia 3 (1) 0 0 0 Nonhematologic Cardiopulmonary failure 0 0 1 (1)† 0 Constipation 1 (< 1)† 0 0 0 Diarrhea 1 (< 1) 1 (< 1) 0 0 Vomiting 1 (< 1)‡ 0‡ 0 0 Nausea 1 (< 1) 0 1 (1) 0 Fatigue 1 (<1) 0 1 (1) 0 General physical health deterioration 1 (< 1) 0 0 0 Multiorgan failure 1 (< 1)† 0 0 0 Pneumonia 1 (< 1)† 0 0 0 Weight decrease 1 (< 1) 0 0 0 Anorexia 1 (< 1) 0 0 0 Musculoskeletal pain 1 (< 1) 0 0 0 Osteonecrosis 1 (< 1) 0 0 0 Pathological fracture 2 (< 1) 1 (< 1) 0 0 Dizziness 1 (< 1) 0 0 0 Primary cancers not tx related Bladder Lymph node mets not originating from prostate Meningioma Squamous cell carcinoma Adenocarcinoma rectosigmoidSkin *Safety population who entered follow-up. †Gr 5. ‡Missing CTC grade.
Temporal Trends in the Proportion of Women Physician Speakers at Major Cardiovascular Conferences
Authors: Celina M. Yong, Sowmya Balasubramanian, Pamela S. Douglas, Prachi Agarwal, Ulrika Birgersdotter-Green, Santosh Gummidipundi, Wayne Batchelor, Claire S. Duvernoy, Robert A. Harrington, Roxana Mehran
Journal: Circulation (2021)
Association of Objectively Measured Timing of Physical Activity Bouts With Cardiovascular Health in Type 2 Diabetes
Authors: Jingyi Qian, Michael P. Walkup, Shyh-Huei Chen, Peter H. Brubaker, Dale S. Bond, Phyllis A. Richey, John M. Jakicic, Kun Hu, Frank A.J.L. Scheer, Roeland J.W. Middelbeek
Journal: Diabetes Care (2021)

Moderate- to vigorous-intensity physical activity (MVPA) improves cardiovascular health. Few studies have examined MVPA timing. We examined the associations of timing of bout-related MVPA with cardiorespiratory fitness and cardiovascular risk in adults with type 2 diabetes.Baseline 7-day hip-worn accelerometry data from Look AHEAD participants (n = 2,153, 57% women) were analyzed to identify bout-related MVPA (≥3 METs/min for ≥10 min). Cardiorespiratory fitness was assessed by maximal graded exercise test. Participants were categorized into six groups on the basis of the time of day with the majority of bout-related MVPA (METs × min): ≥50% of bout-related MVPA during the same time window (morning, midday, afternoon, or evening), <50% of bout-related MVPA in any time category (mixed; the reference group), and ≤1 day with bout-related MVPA per week (inactive).Cardiorespiratory fitness was highly associated with timing of bout-related MVPA (P = 0.0005), independent of weekly bout-related MVPA volume and intensity. Importantly, this association varied by sex (P = 0.02). In men, the midday group had the lowest fitness (β = -0.46 [95% CI -0.87, -0.06]), while the mixed group in women was the least fit. Framingham risk score (FRS) was associated with timing of bout-related MVPA (P = 0.02), which also differed by sex (P = 0.0007). The male morning group had the highest 4-year FRS (2.18% [0.70, 3.65]), but no association was observed in women.Timing of bout-related MVPA is associated with cardiorespiratory fitness and cardiovascular risk in men with type 2 diabetes, independent of bout-related MVPA volume and intensity. Prospective studies are needed to determine the impacts of MVPA timing on cardiovascular health.
Liver‐Specific Deletion of Mouse Tm6sf2 Promotes Steatosis, Fibrosis, and Hepatocellular Cancer
Authors: Elizabeth P. Newberry, Zoe Hall, Yan Xie, Elizabeth A. Molitor, Peter O. Bayguinov, Gregory W. Strout, James A.J. Fitzpatrick, Elizabeth M. Brunt, Julian L. Griffin, Nicholas O. Davidson
Journal: Hepatology (2021)

Background and Aims Human transmembrane 6 superfamily 2 ( TM6SF2 ) variant rs58542926 is associated with NAFLD and HCC. However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased very low density lipoprotein (VLDL) secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver‐specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD. Approach and Results Two independent lines of Tm6 LKO mice exhibited spontaneous hepatic steatosis. Targeted lipidomic analyses showed increased triglyceride species whose distribution and abundance phenocopied findings in mice with liver‐specific deletion of microsomal triglyceride transfer protein. The VLDL triglyceride secretion was reduced with small, underlipidated particles and unchanged or increased apolipoprotein B. Liver‐specific adeno‐associated viral, serotype 8 (AAV8) rescue using either wild‐type or mutant E167K‐Tm6 reduced hepatic steatosis and improved VLDL secretion. The Tm6 LKO mice fed a high milk‐fat diet for 3 weeks exhibited increased steatosis and fibrosis, and those phenotypes were further exacerbated when mice were fed fibrogenic, high fat/fructose diets for 20 weeks. In two models of HCC, either neonatal mice injected with streptozotocin (NASH/STAM) and high‐fat fed or with diethylnitrosamine injection plus fibrogenic diet feeding, Tm6 LKO mice exhibited increased steatosis, greater tumor burden, and increased tumor area versus Tm6 flox controls. Additionally, diethylnitrosamine‐injected and fibrogenic diet–fed Tm6 LKO mice administered wild‐type Tm6 or E167K‐mutant Tm6 AAV8 revealed significant tumor attenuation, with tumor burden inversely correlated with Tm6 protein levels. Conclusions Liver‐specific Tm6sf2 deletion impairs VLDL secretion, promoting hepatic steatosis, fibrosis, and accelerated development of HCC, which was mitigated with AAV8‐ mediated rescue.
Characterization of Acute HCV Infection and Transmission Networks in People Who Currently Inject Drugs in Catalonia: Usefulness of Dried Blood Spots
Authors: Adrián Antuori, Vincent Montoya, David Piñeyro, Lauro Sumoy, Jeffrey Joy, Mel Krajden, Sara González‐Gómez, Cinta Folch, Jordi Casabona, Lurdes Matas, Joan Colom, Verónica Saludes, Elisa Martró
Journal: Hepatology (2021)

Background and Aims Accurate identification of recent HCV infections is critical for tracing the extent and mechanisms of ongoing transmission. We aimed to validate dried blood spot (DBS) samples for the assessment of Hepatitis C virus (HCV) genetic diversity and to determine epidemiological parameters including incidence, determinants of acute infection, and phylogenetic clustering in people who inject drugs (PWID). Approach and Results HCV nonstructural protein 5B next‐generation sequencing was performed from plasma and/or DBS in 220 viremic PWID from the HepC detect II study. No significant differences were found in consensus sequences or Shannon entropy (SE) intrahost diversity estimate between paired plasma/DBS specimens. SE values were used to identify acute infections with 93.3% sensitivity (95% CI, 0.81–1.06) and 95.0% specificity (95% CI, 0.88–1.02) in a set of well‐defined controls. An acute HCV infection (either primary infection or reinfection) was detected in 13.5% of viremic participants and was associated with age ≤30 years (OR, 8.09), injecting less than daily (OR, 4.35), ≤5 years of injected drug use (OR, 3.43), sharing cocaine snorting straws (OR, 2.89), and being unaware of their HCV status (OR, 3.62). Annualized HCV incidence was estimated between 31 and 59/100 person‐years. On phylogenetic analysis, 46.8% of viremic cases were part of a transmission pair or cluster; age ≤30 years (OR, 6.16), acute infection (OR, 5.73), and infection with subtype 1a (OR, 4.78) were independently associated with this condition. Conclusions The results obtained from plasma and DBS characterize PWID with acute infection and those involved in ongoing HCV transmission and allow estimating incidence from cross‐sectional data. This information is critical for the design and assessment of targeted harm reduction programs and test‐and‐treat interventions and to facilitate monitoring of HCV elimination in this key population.
Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing
Authors: Yael C. Cohen, Mor Zada, Shuang-Yin Wang, Chamutal Bornstein, Eyal David, Adi Moshe, Baoguo Li, Shir Shlomi-Loubaton, Moshe E. Gatt, Chamutal Gur, Noa Lavi, Chezi Ganzel, Efrat Luttwak, Evgeni Chubar, Ory Rouvio, Iuliana Vaxman, Oren Pasvolsky, Mouna Ballan, Tamar Tadmor, Anatoly Nemets, Osnat Jarchowcky-Dolberg, Olga Shvetz, Meirav Laiba, Ofer Shpilberg, Najib Dally, Irit Avivi, Assaf Weiner, Ido Amit
Journal: Nature Medicine (2021)
Pretransplant nivolumab further enhanced Treg expansion after posttransplant cyclophosphamide; another aspect for immune tolerance by PTCy after nivolumab
Authors: Shuntaro Ikegawa, Yusuke Meguri, Kentaro Mizuhara, Takuya Fukumi, Hiroki Kobayashi, Yuichi Sumii, Takumi Kondo, Yasuhisa Sando, Miki Iwamoto, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Yuka Fujisawa, Toshi Imai, Yoshinobu Maeda, Ken-ichi Matsuoka
Journal: Leukemia (2021)
Defer vaccination of people who have had covid-19
Authors: Raj Bhopal
Journal: BMJ (2021)

<h3>ABSTRACT</h3> Secreted proteins, which include cytokines, hormones and growth factors, are extracellular ligands that control key signaling pathways mediating cell-cell communication within and between tissues and organs. Many drugs target secreted ligands and their cell-surface receptors. Still, there are hundreds of secreted human proteins that either have no identified receptors (“orphans”) and are likely to act through cell surface receptors that have not yet been characterized. Discovery of secreted ligand-receptor interactions by high-throughput screening has been problematic, because the most commonly used high-throughput methods for protein-protein interaction (PPI) screening do not work well for extracellular interactions. Cell-based screening is a promising technology for definition of new ligand-receptor interactions, because multimerized ligands can enrich for cells expressing low affinity cell-surface receptors, and such methods do not require purification of receptor extracellular domains. Here, we present a proteo-genomic cell-based CRISPR activation (CRISPRa) enrichment screening platform employing customized pooled cell surface receptor sgRNA libraries in combination with a magnetic bead selection-based enrichment workflow for rapid, parallel ligand-receptor deorphanization. We curated 80 potentially high value orphan secreted proteins and ultimately screened 20 secreted ligands against two cell sgRNA libraries with targeted expression of all single-pass (TM1) or multi-pass (TM2+) receptors by CRISPRa. We identified previously unknown interactions in 12 of these screens, and validated several of them using surface plasmon resonance and/or cell binding. The newly deorphanized ligands include three receptor tyrosine phosphatase (RPTP) ligands and a chemokine like protein that binds to killer cell inhibitory receptors (KIR’s). These new interactions provide a resource for future investigations of interactions between the human secreted and membrane proteomes.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Authors: Heng Mei, Xiaofan Liu, Yan Li, Hu Zhou, Ying Feng, Guangxun Gao, Peng Cheng, Ruibin Huang, Linhua Yang, Jianda Hu, Ming Hou, Yazhou Yao, Li Liu, Yi Wang, Depei Wu, Liansheng Zhang, Changcheng Zheng, Xuliang Shen, Qi Hu, Jing Liu, Jie Jin, Jianmin Luo, Yun Zeng, Sujun Gao, Xiaohui Zhang, Xin Zhou, Qingzhi Shi, Ruixiang Xia, Xiaobao Xie, Zhongxing Jiang, Li Gao, Yuansong Bai, Yan Li, Junye Xiong, Runzi Li, Jianjun Zou, Ting Niu, Renchi Yang, Yu Hu
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. Methods Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10 9 /L) after 8 weeks of treatment. Results The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83–68.63; p &lt; 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39–86.87; p &lt; 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. Conclusions In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
Thirty Years of HER3: From Basic Biology to Therapeutic Interventions
Authors: Heidi M. Haikala, Pasi A. Jänne
Journal: Clinical Cancer Research (2021)

Abstract HER3 is a pseudokinase member of the EGFR family having a role in both tumor progression and drug resistance. Although HER3 was discovered more than 30 years ago, no therapeutic interventions have reached clinical approval to date. Because the evidence of the importance of HER3 is accumulating, increased amounts of preclinical and clinical trials with HER3-targeting agents are emerging. In this review article, we discuss the most recent HER3 biology in tumorigenic events and drug resistance and provide an overview of the current and emerging strategies to target HER3.
Long-term Socioeconomic Outcomes Associated With Pediatric-Onset Multiple Sclerosis
Authors: Kyla A. McKay, Emilie Friberg, Neda Razaz, Kristina Alexanderson, Jan Hillert
Journal: JAMA Neurology (2021)

Pediatric-onset multiple sclerosis (PoMS) is associated with significant cognitive and physical disability. Whether this disability translates into differences in educational achievements and earnings is unknown.To evaluate the association between PoMS and educational level and income throughout adulthood.A prospective register-based cohort study of individuals with PoMS and a population-based matched reference cohort was conducted using nationwide microdata from linked registers in Sweden from January 1, 1990, to December 31, 2016; analyses were completed from May 1, 2019, to September 1, 2020. Of 772 persons with PoMS identified in the Swedish MS registry, 485 had an onset during the period from 1980 to 2014 and had socioeconomic data available. The general population reference cohort without multiple sclerosis (MS) (n = 4850) was randomly selected from the full Swedish population, matched 10:1 on age, sex, and country of birth.Pediatric-onset MS, diagnosed by a neurologist, with onset before 18 years of age.Highest educational level (elementary school, high school, or university) was assessed using logistic regression. Income, measured as the mean annual earnings from paid work in US dollars, was compared using Tobit models, and net annual sickness absence and disability pension days were compared using zero-inflated negative binomial regression. Earnings and days receiving disability benefits were compared within 4 age periods (19-24, 25-34, 35-44, and 45-54 years).The median age of the cohort with PoMS (n = 485) and the matched reference cohort (n = 4850) in 2016 was 32 years (interquartile range, 26-40 years), and most participants were women (348 [71.8%] in the PoMS cohort and 3480 [71.8%] in the matched reference cohort). Persons with PoMS were less likely than persons in the matched reference cohort to attend university (odds ratio, 0.80 [95% CI, 0.66-0.97]) and had significantly lower annual earnings than the reference cohort, ranging from -$1618 (95% CI, -$2558 to -$678) in the youngest age period to -$10 683 (95% CI, -$18 187 to -$3178) in the eldest. Persons with PoMS received higher rates of disability benefits, as sickness absence days in the youngest age period (rate ratio, 3.06 [95% CI, 2.08-4.52]) and disability pension days in the oldest age period (rate ratio, 1.43 [95% CI, 1.11-1.85]).This study suggests that having PoMS is associated with less educational achievement, lower earnings, and greater use of disability benefits throughout the working-age life span. As adults, persons with PoMS never earned as much as their counterparts without MS, and they exhibited a heavier reliance on disability benefits.
Invasive and <i>in situ</i> squamous cell carcinoma of the skin: a nationwide study in Iceland
Authors: J.A. Adalsteinsson, E. Olafsdottir, D. Ratner, R. Waldman, H. Feng, J. Ungar, J.I. Silverberg, A.K. Kristjansson, J.G. Jonasson, L. Tryggvadottir
Journal: British Journal of Dermatology (2021)

Background The worldwide incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Objectives To evaluate the tumour burden of in situ and invasive cSCC in Iceland, where the population is exposed to limited ultraviolet radiation. Methods This whole-population study used the Icelandic Cancer Registry, which contains records of all in situ and invasive cSCC cases from 1981 to 2017. Incidence of cSCC was evaluated according to age, anatomical location, residence and multiplicity, and trends were assessed using joinpoint analysis. Age-standardized rates (WSR) and age-specific incidence rates per 100 000 person-years were calculated, along with cumulative and lifetime risks. Results Between 1981 and 2017, in situ cSCC WSR increased from 1·2 to 19·1 for men and from 2·0 to 22·3 for women. Invasive cSCC WSR rose from 4·6 to 14 for men and from 0·3 to 13·2 for women. The average number of in situ cSCC lesions was 1·71 per woman and 1·39 per man. Women developed more in situ cSCCs than invasive cSCCs in almost all anatomical locations, whereas men developed more invasive cSCCs, mostly on the head and neck. The rates of in situ cSCC were higher in Reykjavik compared with rural areas. Furthermore, women more commonly developed multiple in situ lesions. For lip cSCCs, invasive lesions occurred more frequently than in situ lesions among both sexes. Joinpoint analysis showed that in situ cSCC in women exhibited the most rapid incidence increase. Conclusions cSCC has become an increasingly significant public health problem in Iceland. Tanning bed use and travelling abroad may contribute to skin cancer development. Public health efforts are needed to stem the behaviours leading to this rapid rise in cSCC.
A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti–Zika Virus Vaccine
Authors: Nadine C. Salisch, Kathryn E. Stephenson, Kristi Williams, Freek Cox, Leslie van der Fits, Dirk Heerwegh, Carla Truyers, Marrit N. Habets, Diane G. Kanjilal, Rafael A. Larocca, Peter Abbink, Jinyan Liu, Lauren Peter, Carlos Fierro, Rafael A. De La Barrera, Kayvon Modjarrad, Roland C. Zahn, Jenny Hendriks, Conor P. Cahill, Maarten Leyssen, Macaya Douoguih, Johan van Hoof, Hanneke Schuitemaker, Dan H. Barouch
Journal: Annals of Internal Medicine (2021)

Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available.To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate.Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561).United States.100 healthy adult volunteers.Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo.Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model.All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model.The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population.The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges.Janssen Vaccines and Infectious Diseases.
Risdiplam in Type 1 Spinal Muscular Atrophy
Authors: Giovanni Baranello, Basil T. Darras, John W. Day, Nicolas Deconinck, Andrea Klein, Riccardo Masson, Eugenio Mercuri, Kristy Rose, Muna El-Khairi, Marianne Gerber, Ksenija Gorni, Omar Khwaja, Heidemarie Kletzl, Renata S. Scalco, Timothy Seabrook, Paulo Fontoura, Laurent Servais
Journal: New England Journal of Medicine (2021)

Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre–messenger RNA splicing and increases levels of functional SMN protein.