3^rd Annual Congress on Rare Diseases and Orphan Drugs October 30-31, 2017
(10 Plenary Forums - 1 Event)
San Antonio, Texas, USA

Biography:

Jacques P Tremblay has received PhD in Neuroscience from the University of California at San Diego in 1974. Since that time, he has been at Laval University as a Post-doctoral Researcher, Professor and Director of the Department of Anatomy. He is currently a Full Professor in the Department of Molecular Medicine. He has published over 250 scientific articles on hereditary diseases. He has worked specifically on myoblast transplantation as a treatment for Duchenne muscular dystrophy. For the last 3 years, he also worked on gene correction with the CRISPR/Cas9 technology for Duchenne muscular dystrophy, Friedreich's ataxia and Alzheimer’s disease.

Abstract:

The new CRISPR/Cas9 technology permits to induce double strands breaks (DSBs) in the DNA at a specific sequence in the human genome selected by a guide RNA complementary to a 20 nucleotides sequence. These DSBs may be repaired by different process that either permits to knockout a gene or to repair a mutated gene responsible for a hereditary disease. This technique is used in our laboratory to develop therapies for 3 different diseases: duchenne muscular dystrophy (DMD), Friedreich ataxia (FRDA) and Alzheimer disease (AD). DMD is due to the deletion of one or several exons in the DMD gene that leads to a frame shift, a premature stop codon and the absence of the dystrophin protein. By inducing DSBs in the exons that precede and follow the patient deletion, we have been able to delete an additional segment of the gene leading to the formation of a hybrid exon that not only restores the normal reading frame but also restores the normal structure of the internally truncated dystrophin protein. This should thus permit to transform a DMD patient in a mild Becker muscular dystrophy patient. FRDA is due to an increased number of the trinucleotide GAA in intron 1 of the frataxin gene. This leads to a reduced transcription and a reduced production of the frataxin protein. We have used the CRISPR/Cas9 technology to induce DSB before and after the repeat to remove it. This treatment has led to a doubling of the frataxin mRNA and protein and this should be therapeutic in the patients. Hereditary AD is to point mutations in the amyloid precursor protein (APP) gene. Using the CRISPR/Cas9 system, have induced a DSB in that gene and replaced the mutated nucleotides. This could also lead to a potential therapy.

Biography:

Maria Shkrob has 7 years of experience in the bioinformatics industry, working on the solutions for text and data mining. At Elsevier, she works as a Consultant for Elsevier Professional Services applying the rich R&D Solutions portfolio to address customers’ needs.

Abstract:

Statement of the Problem: One of the pressing challenges in drug repurposing for rare diseases is a limited amount of scientific information needed to discover new targets and suggest new treatments. In this field, it is particularly critical not only to aggregate all available evidence about the rare disease but also to be able to fill the gaps with the knowledge from other research areas to generate new ideas and propose new therapeutic approaches.

Methodology & Theoretical Orientation: Elsevier is collaborating with a rare disease charity, Findacure, to provide information about congenital hyperinsulinism to the patients, researchers and doctors, to help finding new treatments, support applications for drug repurposing programs, increase awareness, streamline information exchange and education. Using an integrative approach of automated and manual curation of literature, we provided an overview of the mechanisms, targets, drugs, key opinion leaders and institutions studying the disease. An automated pipeline to generate such summaries was designed to expand the use of the approach and provide scalability.

Findings: Suggested approach was applied to several rare diseases to automatically generate ranked lists of drug repurposing candidates, targets and key opinion leaders.

Conclusion & Significance: We developed a framework to retrieve and aggregate information required to support drug repurposing decisions, facilitate clinical trials and bring together stakeholders. Suggested approach was applied to congenital hyperinsulinism and was replicated two more rare diseases.

Biography:

Amrik Sahota is a Professor in the Department of Genetics, Rutgers University, Piscataway, NJ. He is also a Clinical Professor in the Department of Pathology and Laboratory Medicine and in the Division of Urology, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. He is a fellow of the American College of Medical Genetics and Genomics, National Academy of Clinical Chemistry, Royal Society of Biology (UK), and the Royal College of Pathologists (UK). He is board-certified in Clinical Molecular Genetics by the American Board of Medical Genetics and Genomics and in Molecular Diagnostics by the American Board of Clinical Chemistry. His research interests are in genetic disorders of urolithiasis, mouse models for human disease, and molecular diagnostics.

Abstract:

Background: Cystinuria is characterized by excessive excretion of cystine in the urine and cystine stones in the kidneys and, to a lesser extent, in the bladder. Cystine analogs such as cystine dimethylester (CDME) inhibit cystine crystal growth through binding to specific crystal surfaces, thus providing a novel therapeutic approach for cystinuria. We synthesized a series of L cystine diamides as cystine crystal growth inhibitors that would have greater stability and bioavailability compared with CDME. The most effective inhibitor to date is L cystine bis(Nʹ-methylpiperazide), denoted LH708. Here, we evaluate the effectiveness of LH708 in inhibiting cystine stone formation in Slc3a1 knockout male mice, which serve as a model for cystinuria.

Methods: Mice age three months were screened for bladder stones by computed tomography (CT). Only mice that did not have stones were used for this study. Mice were treated with LH708 (150 µmol/kg) or water alone by stomach tube daily for 60 and CT scans were done on days 30 and 60. Bladder stone volume was determined using image analysis software.

Results: Nineteen mice were treated with LH708 and five of them showed stones at day 30. The same mice were stone-positive at day 60, and there was a significant increase in stone volume between the two scans (28.15 versus 64.70 mm3, p=0.0005). Twenty-four mice were treated with water alone and 15 of them showed stones at day 30. Five of these mice died between the two scans, but an additional three were stone-positive at day 60. There was a significant increase in stone volume at the second scan (20.74 versus 52.67 mm3, p=0.0001). Overall, 26% of mice formed stones in the LH708 group versus 75% in the water group.

Conclusion: These data strongly support the evaluation of LH708 as a potential therapy for cystinuria.

Biography:

Janel Long-Boyle is a Translational Scientist with research interests that include pediatric cancer therapeutics, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial design. The majority of her research resides within the complex setting of hematopoietic cell transplantation (HCT) and focused around chemotherapeutic and immunosuppressive agents used in the preparative regimens of pediatric HCT and gene therapy. More recently, her work aims to facilitate the adoption of population pharmacokinetic models into routine clinical practice to improve patient care. Professionally, she has an established clinical pharmacy practice within the UCSF Pediatric Bone Marrow Transplant Service. She also directs an advanced clinical pharmacology consultation service utilized by members of the UCSF Pediatric Bone Marrow Transplant, Immunology and Oncology Services as well as many external clinical centers worldwide.

Abstract:

Statement of the Problem: Quantitative science is a multidisciplinary approach to studying therapeutics, which emphasizes the integration of the relationships between diseases, drug characteristics, and individual variability across studies/drug development. Historically, the adoption of complex pharmacokinetic models into mainstream clinical practice has been hampered by complicated software and the tendency to develop complex models impractical for clinicians to utilize quickly. However, with recent advancements in technology model-based dosing algorithms can be easily implemented into clinical protocols and used to individualize therapy. For pediatric therapeutics this signifies an important paradigm shift from a pre-defined dose (e.g. mg/kg or mg/m2) to a more tailored, individualized approach to therapy.

Methodology & Theoretical Orientation: The overarching goal of model-based dosing is to effectively treat diseases without acute toxicity and to prevent long-term side effects of drug therapy. In pediatrics the pharmacokinetics of drugs in infants can differ widely between children and adults. Within the first year of life, age-related changes can lead to altered drug disposition. Additionally, the relationship between drug concentration and outcomes may be highly variable across different age groups or disease states. Intervention with hematopoietic cell transplantation (HCT) early in life is often critical to effectively treat several childhood diseases including immunodeficiencies and genetic metabolic disorders. Newborn screening allows for diagnosis and thus interventions such as HCT or gene therapy to be offered early when outcomes are superior. Examples of how model-based dosing can be applied to infants, including the commonly used agents used in the setting of pediatric HCT, will be described.

Conclusion & Significance: Moving away from traditional dosing intensity strategies to model-based dosing allows for tailored drug exposure. Further development of model-based dosing in the setting of HCT has the potential to minimize toxicity while maximizing efficacy, resulting in superior outcomes for children with rare diseases.

Biography:

Shipra Agrawal is an Investigator in the Center for Clinical and Translational Research at The Research Institute at Nationwide Children's Hospital and a Research Assistant Professor in the Department of Pediatrics at The Ohio State University College of Medicine. She is trained in Molecular, Cellular and RNA Biology and mechanistic aspects of human diseases and her research interests have both basic and translational components with a committed focus on kidney disease. Her basic research direction is the identification and modulation of molecular signaling pathways involved in glomerular and podocyte biology and injury, which can potentially translate into novel therapeutic targets for nephrotic syndrome and other glomerular diseases. Her additional translational research focus is on the identification of biomarkers to predict and define steroid resistance in nephrotic syndrome. Her contributions have been published in high impact journals: NEJM, JBC, KI, JASN, HMG, AJHG, JVirol, Virology and NRN.

Abstract:

Statement of the Problem: Nephrotic syndrome (NS) is a kidney disease characterized by proteinuria, edema and increased risk for complications such as infection, acute kidney injury, thrombosis and dyslipidemia. Glucocorticoids (GC) induce remission of NS in most children, though ~20% present with or develop GC resistance. The predictive biomarkers and molecular basis for differences in GC efficacy between steroid-sensitive (SSNS) and steroid resistant (SRNS) children remain largely unknown. This study seeks to determine the predictive biomarkers and mechanisms responsible for differential responses to GC in children with SSNS and SRNS.

Methodology & Theoretical Orientation: Paired plasma samples and total mRNA from leukocytes were collected at presentation (P) and 6-8 weeks later after the first course of GC therapy (F) from children with SSNS (n=30) and SRNS (n=15). Transcriptome profile was generated by deep RNA seq and differentially expressed genes identified by volcano plotting followed by extreme learning machine algorithm. The plasma samples were enriched for low-abundant serum proteins and analyzed by LCMS for generation of proteomics profile. Broad spectrum HNMR data were acquired, binned, and concentration fit for metabolomics analyses. Cytokine profile was generated using a 27-cytokine panel on immulite system.

Findings: Each sample produced ~100 million sequence reads of ~50 bases/read by RNAseq. Transcriptome profile could identify 15,418 genes after filtering, 28 of which were differentially expressed at presentation and 84 upon treatment between SSNS and SRNS. Curation of 215 identified proteins in the samples resulted in 13 predictor and 67 steroid resistance defining markers following Wilcoxon and Mann-Whitney testing. Metabolites most perturbed by treatment included lipoproteins, adipate, tyrosine, valine, alanine, glutamine, glucose, pyruvate and creatine. These could be differentiated in SSNS but not SRNS. Also, elevated malonate levels increased the odds of GC response. Cytokine profile was also altered in the two patient population specifically for IL-8, RANTES and PDGF.

Conclusion & Significance: Different omics approaches could identify candidate biomarkers that can differentiate between the SSNS and SRNS groups at baseline and after treatment. 

Biography:

Tony Zbeidy is a globe trotter French-Lebanese national and a US Graduate Medical Doctor who initially studied in Lebanon and obtained a BS in Biology. He travelled to US, obtained an MD and moved to UK training and working in Romford, Harold Wood and Basildon Hospitals. In 2001, he moved to France and joined Sanofi (Aventis at that time) as Medical Information Officer; in 2003, joined Orphan-Europe as Medical Advisor and 3 years later, established Orphan-Europe FZ LLC subsidiary in Dubai Healthcare City in 2006 as GM MENA, representing 1/3rd of Orphan-Europe total turnover in 2015 and growing. He has a distinguished achievement, having established alone the Middle East Metabolic Group (MEMG) and is organizing its annual meeting since 2004. In 2011, major pharma companies acting in the field of rare disorders such as Genzyme, Biomarin, Nutricia, Merck-Serono, SOBI, Nestle, Synageva, etc, joined in and in 2015, it represented 250 selected metabolic and genetic specialists from the MENA region.

Abstract:

The Middle East and North Africa region, commonly known as MENA, is nowadays the space for geopolitical conflicts and wars. Despite this fact, the MENA region proved most resistant to the recent economic crisis, especially in the rare disorders domain, continuously presenting a relatively steady market growth. Such situation makes of MENA a high potential space for investments in Orphan Drug development. But what makes MENA of particular interest for the development of Orphan Drugs? And what did many governments in the MENA region, which indirectly boosted this potential higher than ever? MENA is a unique region presenting a high consanguinity rate. Knowing that most rare disorders are recessive and that the incidence of recessive disorders correlates with the level of consanguinity, MENA became a mine for patient recruitment and Orphan Drugs clinical development. Moreover, the global awareness around rare disorders drove the governments in the region to put in place national screening programs over the past ten years. Solid from 16 years’ experience in the Rare Disorders Business in MENA and witness of the regional metamorphosis over time, our presentation will illustrate the business rationale dividing MENA target territories into six clusters, reporting regional consanguinity rates and detailing the principal screening programs put in place in the region. Thus, this presentation is intended an open window for rare disorder drug developers to Market Access the MENA region from its different angles being clinical, business, or both.

Biography:

Aya Narita is a Child Neurologist and has her expertise in diagnosis and treatment for neuronopathic lysosomal storage diseases and other neurodegenerative disease. She has a special interest in development of pharmacological chaperone therapy, and has been a Principal Investigator for Investigator-initiated clinical trials.

Abstract:

Gaucher disease (GD) is a lysosomal storage disease caused by mutations in GBA1 that encodes glucocere-brosidase (GCase). The resultant defective GCase leads to accumulation of the substrates, glucosylceramide and glucosylsphingosine. GD has three clinical variants: type 1 is primarily a non-neuronopathic disease whereas type 2 and type 3 are a continuum of neuronopathic ranging from acute (type 2) to subacute (type 3) progressive central nervous system (CNS) degenerative diseases. Visceral (hepatosplenomegaly), hematological (anemia and thrombocytopenia) and bone disease occur in all forms of GD. Enzyme-replacement therapy and substrate-reduction therapy are approved for patients with GD. While these therapies address most of non-neurological manifestations, none are effective against the CNS disease because of its inability to cross the blood-brain barrier. To settle this problem, pharmacological chaperone therapy (PCT) is being investigated. PCT is based on oral administration of small-molecule stabilizer of mutant proteins. Pharmacological chaperones (PCs) selectively bind to the misfolded enzyme in the ER, facilitating the correct folding of the protein and inducing functional recovery. In 2009, ambroxol, a commercially available expectorant, was identified as a PC candidate, and we started to evaluate the safety, tolerability and neurological efficacy of ambroxol in patients with neuronopathic GD. High-dose oral ambroxol had good tolerability, significantly increased lymphocyte GCase activity and decreased glucosylsphingosine levels in the cerebrospinal fluid. Drug resistant myoclonus and seizures also markedly improved. These results suggested that PCT with ambroxol is promising therapy for neuronopathic GD. 

Biography:

Dung-Fang Lee is dedicated to understand cancer pathological mechanisms by using patient-specific iPSCs and/or engineered ESCs. He has established the first human Li-Fraumeni syndrome (LFS) disease model by using LFS patient-specific iPSCs to delineate the pathological mechanisms caused by mutant p53 in osteosarcoma and continues to apply TALENs and CRISPR/Cas9 genome editing tools to create variant p53 mutations in pluripotent stem cells (PSCs; e.g., iPSCs and ESCs) in order to explore the role of mutant p53 in osteosarcomagenesis. He also works on modeling other familial cancer syndromes with osteosarcoma predisposition by both iPSCs and PSCs. Currently, he applies whole genome sequencing, screening approaches and systems-level analyses to explore early genomic alterations and to understand dynamic alterations of the genomic landscape of LFS-associated osteosarcomas.

Abstract:

Li-Fraumeni syndrome (LFS) is a genetically inherited autosomal dominant cancer syndrome characterized by multiple tumors within an individual, early tumor onset and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS patients present with a variety of tumor types, including osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Germline mutations in the p53 tumor suppressor gene are responsible for LFS. Mutations in p53 are found in 50-70% of human tumors. Although there has been extensive research on cancer cell lines and even mouse models of LFS to study the role of p53, these model systems do not fully recapitulate the range of human tumors or their properties. Here, we established human LFS disease model by using LFS patient induced pluripotent stem cells (iPSCs), to delineate the pathological mechanisms caused by mutant p53 in osteosarcoma. The osteoblasts, differentiated from LFS iPSC-derived mesenchymal stem cells (MSCs), recapitulate osteosarcoma features including defective osteoblastic differentiation and tumorigenic ability, suggesting that my established LFS disease model is a “disease in a dish” platform for elucidating p53 mutant-mediated disease pathogenesis. The gene expression patterns of LFS osteoblasts are similar to those of tumor samples obtained from osteosarcoma patients and these tumorigenic features strongly correlate with shorter tumor recurrence times and poorer patient survival rates. Our functional studies implicate the essential H19 gene in normal osteogenesis and inhibition of tumorigenesis. In order to decipher the underlying mechanisms by which H19 mediates osteogenesis and tumor suppression, we characterized and analyzed the human imprinted gene network (IGN) and revealed the unidentified role of p53 in regulating the IGN culminating in osteogenic differentiation defects and tumorigenesis. In summary, these findings imply the feasibility of studying inherited human cancer syndromes with iPSCs.

Biography:

David Dongliang Ge is the CEO and President of Apostle Inc., in Sunnyvale, CA, focusing on novel bioinformatics-enabled nanotechnologies for cancer early detection. Previously, he was the President of BioSciKin Co. and Simcere Diagnostics Co., China focusing on the licensing and sales of diagnostic technologies. Between 2011 and 2016, he was the Director of Bioinformatics at Gilead Sciences, where he founded and provided leadership to the bioinformatics group and provided the strategic input to related infrastructure and process. He and his group led the phylogenomic analytical support for the critical regulatory approval of Sovaldi, a world-leading anti-HCV drug. In 2014 and 2015, he was invited to be a Member of the US National Human Genome Research Institute Special Emphasis Panel. Prior to Gilead, he was appointed as Assistant Professor of Biostatistics and Bioinformatics and Assistant Professor in Medicine at Duke University School of Medicine. He has received his PhD in Biostatistics and Genetic Epidemiology from Peking Union Medical College and Chinese Academy of Medical Sciences in 2004. He has authored or co-authored over 70 peer-reviewed articles.

Abstract:

The biotechnology industry has quickly entered an era when fast evolving genome technologies, historical precision medicine initiatives and disruptive bioinformatics techniques synergistically start to provide pivotal and strategic support for new drug and diagnostics development. Unprecedented amount of data is being generated to help discover and develop new generations of medications. Using real-world examples, this talk covers several of the most important bioinformatic considerations in this strategy, which include: How do we efficiently manage the massive amount of data at different levels of precision to ensure a seamless data flow? How do we annotate and present these data to make it more comprehensible and deliverable? How do we design and execute the new clinical trials more efficiently and improve the success rate? Where are we and where are we going in this new precision medicine era?

Biography:

Arnab Ghosh is currently a Post-graduate student in Internal Medicine, Armed Forces Medical College, India. His areas of interests are cardiology, endocrinology, hematology and neurology.

Abstract:

Hoffman’s syndrome is a rare and atypical presentation of hypothyroidism, is characterized by pseudo-hypertrophy and stiffness of muscles, myxoedematous features. Long standing hypothyroidism can cause pituitary hyperplasia which is difficult to distinguish with pituitary adenoma even with contrast MRI. We describe a case of a 48 years old male with long standing uncontrolled primary hypothyroidism presenting as Hoffman’s syndrome with reactive pituitary hyperplasia that mimicked a pituitary macroadenoma. We report a case of 48 years-old man, an old case of hypothyroidism (onset 2005) with poor drug compliance presented with progressive proximal muscular weakness with muscle cramps and myalgia, swelling of all four limbs, dark pigmentation of several body parts involving face, increased hair fall, change in voice, increased body size and memory loss. Clinical examination revealed macroglossia, infiltrated facies, hoarse voice, increased soft tissue mass all over body specially face, limbs and trunk, dark pigmentation of face, legs, oral mucosa and nails, Pseudo-herculean appearance, hypertrophy of muscles with an athletic look. Neurological examination revealed pseudo-hypertrophy with proximal paresis of lower limb muscles and generalized hyporeflexia. Laboratorial investigation revealed increased CPK, mild elevation of serum level of creatinine, dyslipidemia, high TSH, low T3 and T4 with raised levels of anti thyroid-peroxidase antobodies. NCS was normal. DXA scan revealed increased fat composition. MRI brain revealed pituitary mass. After 20 days of thyroid hormone therapy, the patient had improvement of the muscular cramps. After 03 months of active therapy a repeat MRI was done which showed regression of size of the mass. In a case of primary hypothyroidism with a solid mass lesion of the pituitary gland, pituitary hyperplasia secondary to hypothyroidism rather than pituitary adenoma should be excluded to avoid unnecessary surgical intervention which has its own complications. 

Biography:

Abhish Mohan has his interest in hematolymphoid malignancies and has passion to improve the diagnostic capabilities of resource limited countries which will benefit a large number of people. His other areas of interest include Military Medicine with special emphasis in high altitude medicine.

Abstract:

Angioimmunoblastic T-cell lymphoma (AITL) is one of the rare sub-types of peripheral T-cell lymphoma, comprising 2-5% of all non-Hodgkin lymphomas. AITL is associated with many systemic features like fever, rash or arthritis. These systemic features may precede the appearance of other features of lymphoma. The disease may present with autoimmune phenomena, such as the presence of circulating immune complexes, cold agglutinins, hemolytic anemia and rheumatoid factor and anti-smooth muscle antibodies. In approximately half of the patients, polyclonal hypergammaglobulinemia is present. Vasculitis is not common but comprises antineutrophil cytoplasm antibodies (ANCA) negative vasculitis. A 65 year old male presented with complaints of a short febrile illness associated with weight loss, dry cough, generalized weakness, pruritus and paresthesias of bilateral lower limb. He was admitted to medical ward and after 12 hours patient developed dyspnea and blackish discoloration of digits. Clinical examination revealed scattered polyphonic wheeze over bilateral chest. A working diagnosis of secondary vasculitis was made and was started on methylprednisolone pulse in view of impending digital gangrene. He responded to the treatment with no further progression of digital ischemia. Autoimmune workup revealed pANCA strongly positive by ELISA; however ANA, DCT/ICT was negative. Chest and abdomen showed hepatosplenomegaly with hilar and pretracheal lymphadenopathy. Serum protein electrophoresis revealed monoclonal gammopathy, IgG lamda restricted. A lymph node biopsy of left axilla was done and HPE was suggestive of angioimmunoblastic T-cell lymphoma. He was started on chemotherapy CHOP and has shown response. AITL is one of the uncommon but aggressive neoplasms which have a varied clinical presentation including constitutional symptoms, lymphadenopathy, organomegaly, autoimmune phenomena especially hemolytic anemia and thrombocytopenia and polyclonal hypergammaglobulinemia. This case emphasizes the atypical presentation of a rather rare disease and the need for high index of suspicion, which will help in initiating chemotherapy well in time and to prolong median survival.

Biography:

Arnab Ghosh is currently a Post-graduate student in Internal Medicine, Armed Forces Medical College, India. His areas of interests are cardiology, endocrinology, hematology and neurology.

Abstract:

POEMS syndrome, also known as Osteosclerotic Myeloma, Takatsuki syndrome or Crow-Fukase syndrome, is a very rare paraneoplastic presentation associated with plasma cell dyscrasias. The acronym stands for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes. We report a case of 65 years old post-menopausal lady presenting with insidious onset, gradually progressive sensory loss and paresthesia of lower limbs with significant weight loss, hypertrichosis and hyperpigmentation of skin on sun exposed areas. Examination revealed non length dependent pure sensory large fiber neuropathy with diminished reflexes and hypotonia of lower limbs hyperpigmentation of skin, hypertrichosis and hepatomegaly. Investigations showed polycythemia, demyelinating peripheral neuropathy on NCS, monoclonal gammopathy IgG lambda on SPEP and IF, low serum cortisol, raised FSH, LH and prolactin, recent onset diabetes, obstructive lung disease, hepatomegaly and sclerotic bone lesions. Skin biopsy showed increased melanin without increase in melanocytes and normal cardiac function. She was diagnosed as a case of POEMS syndrome based on Mayo clinic criteria and started on Aspirin, Lenaledomide and Prednisolone. Post-treatment, her symptoms improved remarkably. Paresthesia is a very common presentation of many diseases. It can be a part of paraneoplastic syndrome. One should not miss the diagnosis of any occult malignancy like in this case. Monoclonal gammopathies should always be ruled out in elderly. Patients with POEMS syndrome have hyperviscosity due to polycythemia and thrombocytosis which may be accompanied by volume overload state secondary to VEGF mediated capillary leak. Care should be taken for the prevention of thrombosis and congestive cardiac failure. Though rare, POEMS syndrome should be properly identified and reported as the treatment and prognosis of this entity is entirely based upon case reports available till date. More information based upon case reports will help formulate guidelines on therapy for POEMS.