Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 4th World Congress on Rare Diseases and Orphan Drugs Dublin, Ireland.

Day 1 :

Conference Series Rare Diseases Congress-2018 International Conference Keynote Speaker Laxminarayan Bhat photo
Biography:

Laxminarayan Bhat, PhD, is the Founder, President, and Chief Executive Officer of Reviva Pharmaceuticals, Inc. Dr. Bhat founded Reviva in 2006 and since its inception, the company has advanced rapidly under his leadership with a portfolio of propriety compounds at different stages in a pipeline encompassing central nervous system (CNS), cardiovascular, and inflammatory diseases. Dr. Bhat has over 20 years of experience in drug discovery and development, and prior to founding Reviva, he held research positions at XenoPort, ARYx Therapeutics, and Higuchi Biosciences Center in the United States. Dr. Bhat conducted extensive graduate and post-graduate training in medicinal chemistry in India, France, Germany, and USA. Dr. Bhat has published over 25 research papers in peer reviewed international journals and has given several invited lectures/presentations in national and international conferences. Dr. Bhat is an inventor with over 60 granted patents and contributed to one approved drug currently in the market worldwide

Abstract:

Pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) are two progressive, debilitating, and fatal lung diseases. Both diseases are limited in treatment options and have no cure. Pulmonary hypertension, inflammation, and structural remodeling, all with varying degrees of severity, are the most common and significant underlying pathophysiologic factors associated with these conditions. Although the pathogenesis is not clearly understood, increased levels of inflammatory cytokines, including growth factors and dysfunctional endothelial vasoactive mediators (e.g., serotonin, 5-HT; endothelin, ET; nitric oxide, NO; and prostacyclin, PGI2), are found in the lungs of PAH and IPF patients. The 5-HT receptor signaling pathway appears to play a central role in the pathobiology of both conditions. RP5063, a new chemical entity, is a potent modulator of 5-HT signaling that involves specifically the 5-HT2A/2B/7 receptors within the lung. The signal transduction pathways involving these 5-HT receptors mediate significant underlying pathophysiology (vasoconstriction, and vascular/alveolar inflammation, fibrosis, and proliferation) for PAH and IPF. RP5063 has demonstrated proof of concept in translational animal models that emulate IPF and PAH in humans. The U.S. FDA has granted an Orphan Drug Designation to RP5063 for the treatment of PAH and IPF, in which clinical phase 2 studies are planned to start soon. This presentation will briefly review approved therapies and unmet medical needs for PAH and IPF. It will segue to the current understanding of 5-HT receptor signaling pathways in the pathobiology of these two diseases, and will then discuss RP5063 pharmacology and preclinical efficacy for PAH and IPF. It will close by delineating the clinical pharmacokinetic/ pharmacodynamic and safety profiles of this compound

Keynote Forum

Gianluca Colella

Rizzoli Orthopaedic Institute
Italy

Keynote: Surgical treatment of early onset scoliosis associated with Rare Disease

Time : 11:00-11:40

Conference Series Rare Diseases Congress-2018 International Conference Keynote Speaker Gianluca Colella photo
Biography:

Gianluca Colella is specialized works in Orthopaedics and Traumatology at University Federico II – Napoli, Fellow at Spine Surgery Division - Istituto Ortopedico Rizzoli.He has done his Master Degree in Medicine and Surgery at University Federico II Naples, with a discussion “Trattamento chirurgico e tecniche ricostruttive dei tumori del femore prossimale: limb salvage surgery", and also Abilitation to Medical and Surgical Profession. . He is also responsible for a specialized clinic dedicated to the study and treatment of severe spinal deformities associated with rare diseases at the Rizzoli Orthopedic Institute

Abstract:

Background: Kyphoscoliosis is the most common and rapidly  evolving spinal deformity in rare syndromes. Early Onset and  Congenital deformities, often associated with a lot of malformation, are difficult to manage. The aim of the study is to describe an approach to spinal deformities in rare syndromes and assess the effectiveness of growing systems.
Methods: We report 11 cases of pediatric patients with scoliosis (7 males, 4 females) : 2 NF1, 2 arthrogryposis, 1 Spondylo-rib dysplasia, 1 trisomy 8, 1 syringomyelia, 1 Arnold Chiari type I, 1 Prader Willi, 1 Kabuki syndrome, 1 Escobar. This is a retrospective study from 2006 to 2011. The inclusion criteria were 1) EOS or congenital scoliosis in rare disease, 2) Growing rod system, 3) followup 24 months (12-36) . Surgery was performed using VEPTR in 4 patients (Mean age 1st visit: 3 yy (1-7) at surgery: 5 yy (3-9), GROWING ROD in 7 patient (Mean age 1st visit: 6 yy (3-10) at surgery: 9 yy (5-12)
 
Results: The patients were clinically and radiologically reviewed at a mean follow-up of 11 months. We made 11 first surgery and 15 lengthening procedures. The thoracic curve correction was of 50% ( from 65° to 39°). Children are grown on average of 2,5 cm/ each follow up year, results so similar to the phisiological growth. We had 8 postoperative mechanical complications on 26 surgeries: 4 screws loosening, 3 broken rods, 1 rib-hook loosening; 6 cases were treated during the planned lenghthening and 2 with revision
surgery not originally planned.
 
Conclusions: Our strategy is for each patient working in team, with other colleagues more specialist and a particular route starts from a dedicate ambulatory (Rare disease ambulatory). The first step is to be aware of the specific diagnosis of a suspected syndrome; without a confirmed genetic diagnosis of a suspected syndrome, it is impossible to plan preoperative strategy for major spine surgery to minimize the risk of increased morbidity and mortality due to the syndrome.The preoperative programs need a particular flow chart with all exams to study the case, such as X-Rays, MRI, Cardio and abdominal US, CT scan, anaesthesiologist, neurological, pneumological visits. The growing systems are good tools and effective in the treatment of early-onset scoliosis in rare syndromes. Early surgical treatment is needful for these deformities that don’t respond at the conservative treatment. The correction rate depends on the age at first surgery and earlier we start better will be the results.

 

Keynote Forum

Abdulaziz Aldawood

King Saud Bin Abdulaziz University
Saudi Arabia

Keynote: Clinical Course and Outcomes of Critically Ill Patients With Middle East Respiratory Syndrome Coronavirus Infection

Time : 11:40-12:20

Conference Series Rare Diseases Congress-2018 International Conference Keynote Speaker Abdulaziz Aldawood photo
Biography:

Deputy Chairman, Intensive Care Department, Consultant, Pulmonary and Critical Care Medicine, Professor, King Saud Bin Abdulaziz University for Health Sciences,Riyadh, Kingdom of Saudi Arabia, Dr. AlDawood graduate from College of Medicine in Kingdom of Saudi Arabia. Then he completed the Residency in Internal Medicine Program in McMaster University in Canada He obtained Critical Care and Respirology Fellowship Program in McMaster University, Canada (Jul 97-Jun 00). In July 2000, he joined King Abdulaziz Medical City, Riyadh, Saudi Arabia as a Consultant in Critical Care and Pulmonary Medicine up to the present. He is currently the Deputy Chairman of the Intensive Care Department and Professor in King Saud Bin Abdulaziz University for Health Sciences. In addition, he has more than 40 publications including articles in the New England Journal of Medicine (NEJM), JAMA, American Journal of Respiratory Critical Care Medicine, BMC Anesthesiology, and Critical Care Medicine

Abstract:

Background: Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) havebeen reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited.
Objective: To describe the critical illness associated with MERS-CoV.
Design: Case series.
Setting: 3 intensive care units (ICUs) at 2 tertiary care hospitals in
Saudi Arabia.
Patients: 12 patients with confirmed or probable MERS-CoV infection.
Measurements: Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity
of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure.
Results: Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care–associated cluster that also
included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury,
and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive.
Limitation: The sample size was small.
Conclusion: MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extra pulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care–associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care–associated cluster suggests that human-to-human transmission does occur with unprotected exposure.

  • Track 1: Neglected Tropical Diseases
    Track 2: Rare Pulmonary Diseases
    Track 3: Rare Diseases in Neurology
    Track 4: Rare Genetic Diseases
    Track 5: Scope of Orphan Drugs
    Track 6: Rare diseases of Endocrine System
    Track 7: Rare diseases of Immune System
    Track 8: Rare Cardiac Diseases
    Track 9: Rare Eye and Ear Diseases
    Track 10: Orphan Drugs Treatment for Rare Diseases
    Track 11: Rare Oral Diseases
    Track 12: Rare Hepatic Diseases
    Track 13: Rare Gastrointestinal Diseases
    Track 14: Rare Bacterial, Viral and Fungal infections
    Track 15: Rare diseases of Genitourinary System
    Track 16: Rare diseases in Nephrology
Location: Dublin, Ireland

Session Introduction

Yolande van Bever

Erasmus Medical Centre
The Netherlands

Title: Rare diagnosis in disorders/differences of sex development
Speaker
Biography:

Yolande van Bever is a clinical geneticist with expertise in congenital anomalies and syndromes and with a special interest in the field of DSD. She worked in various academic hospitals in the Netherlands and abroad. Since 2004 she is an active team member not only in the clinical genetic staf, but also in various multidisciplinary teams such as the follow up team on surgical congenital anomalies, the neurofibromatosis team and the DSD team. In view of the rapid growing diagnostic genetic possibilities it is important to focus on communication with patients and their caretakers

Abstract:

DSD (Disorders/Differences of Sex Development) comprise a rare group of diseases and abnormalities that can present on different ages and have very variable presenting symptoms. Prenatally discrepancy between genotypic sex and ultrasound phenotype or an abnormal genital as seen by ultrasound. Neonatal or pediatric symptoms can be a genuine ambiguous genital, inguinal (ovotestes) in a girl detected during inguinal hernia surgery, small stature in a 45,X/46 XY girl etc. Others are only detected at puberty or when trying to get pregnant.

There is consensus that patients should be evaluated by multidisciplinary teams and that it is important to involve patients or caretakers in the process of diagnosis and management. Psychological, socio-cultural and economic-organizational aspects play an important role.

Within the group of diagnosis that fall under the term DSD, there are well-known syndromes as Turner syndrome and variants, CAH, or proximal hypospadias, which can have many causes and can present as ambiguous genitalia. Other causes are very rare and may not be easily recognized. Some of these will be presented here. The experience and organization of our team and DSD care in the Netherlands and the place and timing of NGS based diagnostics will be discussed.

For the future it is important to realize the importance of choosing the right words to communicate about the condition, especially also for professionals who have little or no experience with DSD but who are frequently the first to see the patient. Transition from prenatal care to postnatal professionals, from a peripheral clinic to a specialized clinic or from adolescent to adult specialists often offers room for improvement. We should not neglect that in these exciting times of growing diagnostic possibilities

Gianluca Colella

Rizzoli Orthopaedic Institute
Italy

Title: Surgical treatment of scoliosis in rare diseases: Arthogryposis

Time : 12:50-13:20

Speaker
Biography:

Gianluca Colella is specialized works in Orthopaedics and Traumatology at University Federico II – Napoli, Fellow at Spine Surgery Division - Istituto Ortopedico Rizzoli.He has done his Master Degree in Medicine and Surgery at University Federico II Naples, with a discussion “Trattamento chirurgico e tecniche ricostruttive dei tumori del femore prossimale: limb salvage surgery", and also Abilitation to Medical and Surgical Profession. . He is also responsible for a specialized clinic dedicated to the study and treatment of severe spinal deformities associated with rare diseases at the Rizzoli Orthopedic Institute.

Abstract:

Background: The reported incidence of scoliosis in arthrogryposis varies from 30% to 67% and, in most cases, the curves progress rapidly and become stiff from early age. The authors report six cases of scoliosis in arthrogryposis to assess the role of surgical treatment.
Methods: Six cases (3 males, 3 females; mean age at surgery 13.2 years) with arthrogryposis multiplex congenital associated with the characteristic amyoplasia were reviewed: they were operated on for scoliosis at the authors’ Spine Surgery Department between 1987 and 2008. Surgery was performed using the Harrington-Luque instrumentation (2 cases), the Luque system (1),
a hybrid segmental technique with hooks and screws (1) and spinal anchoring with pedicle screws (2)
Results: The patients were clinically and radiologically reviewed at a mean follow-up of 4.2 years, ± 2.7 (range, 1 to 9 years). Three minor postoperative complications were encountered; a long-term pulmonary complication was seen in one case after reintervention and was successfully resolved after 10 days. Surgery was successful in the other 5 cases, where solid arthrodesis
was achieved and no significant curve progression was observed at followup.
Conclusions: The experience acquired with the present case series leads the authors to assert that prompt action should be taken when treating such aggressive forms of scoliosis. In case of mild spinal deformities in arthrogryposis, brace treatment should be attempted, the evolution of the curves being unpredictable; however, when the curve exceeds 40° and presents with marked hyperkyphosis, hyperlordosis or pelvic obliquity, surgery should not be delayed.

Speaker
Biography:

Laxminarayan Bhat, Ph.D., is the Founder, President, and Chief Executive Officer of Reviva Pharmaceuticals, Inc. Dr. Bhat founded Reviva in 2006, and since its inception, the company has advanced rapidly under his leadership with a portfolio of propriety compounds at different stages in a pipeline encompassing central nervous system (CNS), cardiovascular, and inflammatory diseases. Dr. Bhat has over 20 years of experience in drug discovery and development. Prior to founding Reviva, he held research positions at XenoPort, ARYx Therapeutics, and Higuchi Biosciences Center in the United States. Dr. Bhat conducted extensive graduate and post-graduate training in medicinal chemistry in India, France, Germany, and the USA. Dr. Bhat has published over 25 research papers in peer-reviewed international journals. He has given several invited lectures/presentations at national and international conferences. Dr. Bhat is an inventor with over 60 granted patents and contributed to one approved drug currently in the market worldwide

Abstract:

Pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) are two progressive, debilitating, and fatal lung diseases. Both conditions are limited in their treatment options and have no cure. They share some common underlying pathophysiologic features with varying degrees of severity. The major ones include pulmonary hypertension, inflammation, and structural remodeling. Developing pharmacological treatments for these lung diseases is a challenging task as the pathogenesis is not clearly understood. There are three classes of drugs widely used often in combinations for the treatment of PAH: (1) phosphodiesterase 5 (PDE-5) inhibitors; (2) endothelin receptor antagonists; and (3) prostanoids. These drugs are pulmonary vasodilators and do not reverse the structural changes in the pulmonary vascular bed. Therefore, the current treatments are not effective in preventing or delaying the progression of PAH. Similarly, there are two drugs (nintedanib and pirfenidone) approved for the treatment of IPF. They are not effective in significantly delaying the progression of this condition. Also, the majority of these lung disease patients suffer from chronic mental and metabolic comorbidities. The average lifespan of patients after diagnosis for PAH is 5-7 years and for IPF 3 years. Thus, there is a significant unmet medical need and growing demand to develop novel treatments that can significantly delay the disease progression, if not to provide a cure, and to improve patient quality of life. This presentation will briefly review current understanding of the pathobiology of PAH and IPF, approved
therapies, unmet medical needs, and novel treatments in development in the industry. This discussion will examine some the translational challenges involved in the development of new therapeutic options and the lessons learned. Finally, it will close by (1) delineating the concerns related to intellectual properties and commercialization and (2) by providing insight into future directions in the management of these conditions.
 

Speaker
Biography:

Tatjana Michel works with synthetic modified mRNA treatment strategy since 2013. Her work is focused on the development and evaluation of mRNA-based drugs for rare monogenetic diseases like alpha-1-antitrypsin deficiency or familial hypercholesterolemia. Prior to that, she worked on strategies for cell transdifferentiation for heart regeneration and investigated immunogenic effects caused through synthetic nucleic acids

Abstract:

Alpha-1-antitrypsin deficiency (AATD) is one of the most common monogenic diseases worldwide. A mutation in alpha-1- antitrypsin (AAT) protein causes the protein to misfold and accumulate in hepatocytes instead of being secreted into the blood stream. This deprives the lungs from AAT protein, which plays a protective role against neutrophil elastase proteolytic activity. Both the accumulation in the hepatocytes and absence from lung lead to permanent irreversible tissue damage in the form of cirrhosis and pulmonary emphysema. Currently, AATD patients receive an AAT protein replacement therapy but it
comes at undesirable side effects and high costs. In addition, gene therapy approaches are tested in clinical trials but with serious immunogenic, mutagenic and carcinogenic consequences. Therefore, a novel therapeutic strategy based on messenger RNA (mRNA) was established, which can be used to achieve a targeted and controllable induction of AAT expression in target cells. First, an AAT-encoding mRNA was generated and tested in vitro. Here, it could be shown that the AAT mRNA is translated into a bioactive protein capable of efficiently inhibiting neutrophil elastase. Furthermore, the encapsulation of mRNA into nanoliposomes was optimized for later in vivo use. These nanoliposomes were prepared from a cationic and a neutral lipid and analyzed for mRNA encapsulation capacity, transfection efficiency, immunogenicity, biocompatibility and hemocompatibility. Compared to Lipofectamine 2000, a significantly higher translation of the AAT protein was detected during the in vitro experiments using prepared nanoliposomes. In addition, after incubation with the liposomes, cells showed no adverse effects on viability and no upregulation of innate immune defense genes. Furthermore, no negative effects could be observed in the form of complement system, leukocyte and platelet activation. This work lays the foundation for comprehensive mRNA-based therapeutic strategy for AATD patients and could serve as an alternative to protein replacement therapy and gene therapy in clinical use.

Speaker
Biography:

Dr.Alan Gilstrap has experience in the pharmaceutical industry with previous leadership roles at Akcea Therapeutics. He was intricately involved in the design and refinement of the study survey as well as being largely responsible for study approval and access in the United States and Canada

Abstract:

Synopsis: FCS is a rare genetic disease characterized by extreme hypertriglyceridemia due to high chylomicron accumulation in the plasma. Burden of illness previously reported in the InFOCUS study, showed patients with FCS report psychosocial symptoms including anxiety, fear/worry, cognitive impairment, and physical symptoms including fatigue, abdominal pain, acute and recurrent pancreatitis. Community support and mentorship, either in-person interactions or online patient/caregiver forums, play an important role in helping patients manage their rare disease needs and associated psychosocial challenges. There is little current research assessing the impact of being connected to FCS-specific networks on the quality of life (QoL) in patients with FCS.

Objective: Assess the possible impact of connections and patient/caregiver engagement with patient advocacy groups and social media platforms on QoL of patients with FCS.

Methods: A web-based survey was designed to assess the level of social connectedness for patients/caregivers. Participants identified as having FCS or caregivers for FCS patients, were classified as being ‘actively’ (participating ≥once every 2wks) or ‘passively’ (participating

Results: Preliminary data, from limited participants (n=10), indicate that 70% of respondents were actively connected to peers via FCS-specific networks. Time spent connected to various networks ranged from 7.8-24 months. Respondents reported better overall health after being connected to FCS-specific networks. Patients reported improvements in mental, emotional/psychosocial symptoms related to FCS after being connected. Early data from connected patients showed a trend towards improved social relationships, and higher QoL satisfaction. Evidence from preliminary data indicates respondents show a trend towards reduction in perception of FCS severity.

Conclusion:

Preliminary self-reported data indicates support/connection through FCS-specific networks show a positive-trend in improving overall health and social relationships, and reducing anxiety levels and depression in patients with FCS and their caregivers.