rarediseasehighlight

Rare Disease Highlight: Sanfilippo Syndrome

Named after Dr. Sylvester Sanfilippo in 1963, Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a lysosomal storage disease affecting the central nervous system of young children. This disease is caused by an autosomal recessive mutation in one of four enzymes required to break down large chains of sugar molecules called glycosaminoglycans (GAGs). These molecules are located in the cells of the nervous system and help build connective tissues in the body1. As a result of the genetic mutation, GAGs remain stored in the cells of the nervous system, causing progressive developmental damage. Sanfilippo syndrome often goes undetected for years and most children with the disease are born with no visible signs of the disease2. Symptoms such as developmental disabilities, movement disorders, significant hyperactivity, and seizures begin to appear after age 1, and learning abilities begin to slow between ages 2 and 63. Sanfilippo syndrome is rare, with an incidence of 1 in 70,000 births worldwide4. Because there is no cure or currently approved treatment, disease management or palliative care are implemented to treat symptoms, and life expectancy is typically around 15 years5.

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References used
  1. MPS III. MPS Society. https://mpssociety.org/learn/diseases/mps-iii/. Accessed July 18, 2019.
  2. Fedele AO. Sanfilippo syndrome: causes, consequences, and treatments. Appl Clin Genet. 2015;8:269-281. doi:10.2147/TACG.S57672
  3. Reference GH. Mucopolysaccharidosis type III. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii. Accessed July 18, 2019. .
  4. Zelei T, Csetneki K, Vokó Z, Siffel C. Epidemiology of Sanfilippo syndrome: results of a systematic literature review. Orphanet J Rare Dis. 2018;13. doi:10.1186/s13023-018-0796-4
  5. Sanfilippo Children’s Foundation – What is Sanfilippo? https://www.sanfilippo.org.au/page/26/what-is-sanfilippo. Accessed July 18, 2019.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Rare Disease Highlight: Microvillus Inclusion Disease

Microvillus inclusion disease (MVID) is a congenital intestinal disorder characterized by chronic, severe, and watery diarrhea due to insufficient absorption of nutrients during digestion. Two forms of MVID have been identified: early-onset MVID, which develops within hours or days of birth, and late-onset MVID, which occurs in the first months of life1. Affected infants experience malnutrition, dehydration, developmental delays, and severe metabolic acidosis. The cause of MVID is unknown, however, the disease can be attributed to mutations in the MYO5B gene which result in abnormal microvilli, which reduce the intestine’s ability to absorb necessary nutrients and fluids. While the exact prevalence of MVID is unknown, the disease is extremely rare with less than 200 cases reported in Europe since it was first described in 1978 by GP Davidson3.  No medical treatment has been successful in overcoming MVID-associated intestinal failure. Affected infants remain dependent on total parenteral nutrition or intravenous replacement of fluid and electrolytes life-long4. Due to the severity of the disease, the prognosis for MVID is poor as a result of severe dehydration, metabolic imbalance, and sepsis5.

References used
  1. Microvillus inclusion disease. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/microvillus-inclusion-disease. Accessed July 12, 2019.
  2. RESERVED IU–AR. Orphanet: Microvillus inclusion disease. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=2290&lng=EN. Accessed July 12, 2019.
  3. Towards understanding microvillus inclusion disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733813/. Accessed July 12, 2019.
  4. Bunn SK, Beath SV, McKeirnan PJ, et al. Treatment of Microvillus Inclusion Disease by Intestinal Transplantation. Journal of Pediatric Gastroenterology and Nutrition. 2000;31(2):176.
  5. Ruemmele FM, Schmitz J, Goulet O. Microvillous inclusion disease (microvillous atrophy). Orphanet J Rare Dis. 2006;1:22. doi:10.1186/1750-1172-1-22

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Rare Disease Highlight: Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most commonly observed form of idiopathic interstitial pneumonia, an aging-associated, progressive, chronic, and irreversible lung disease with very limited therapeutic options 1,2. IPF is characterized by progressive scarring of the lungs causing respiratory failure and death. The exact cause of IPF is unclear, although there are some environmental and genetic risk factors to the disease including middle-to-older age, smoking, and chronic inflammation 1,3. Symptoms of IPF include shortness of breath after exertion combined with dry cough. As the disease progresses, discoloration of the skin and signs of right ventricular failure may occur together with respiratory failure, eventually leading to death 4Currently there are no approved therapies for the treatment of IPF, however supportive therapies are available to manage symptoms. IPF is rare, with an estimated incidence rate of 2.8-9.3 per 100,000 per year in North America and a low survival of only 20% for five years 5.

References used
  1. Pardo, A. & Selman, M. Lung fibroblasts, aging, and idiopathic pulmonary fibrosis. Ann. Am. Thorac. Soc. 13, S417–S421 (2016).
  2. Zieliński, M., Sitek, P. & Ziora, D. Idiopathic pulmonary fibrosis coexisting with lung cancer — a review. Adv. Respir. Med. (2015). doi:10.5603/ARM.a2018.0052
  3. Kaunisto, J., Salomaa, E., Hodgson, U., Kaarteenaho, R. & Myllärniemi, M. Idiopathic pulmonary fibrosis – a systematic review on methodology for the collection of epidemiological data. 1–11 (2013). doi:10.1186/1471-2466-13-53
  4. Sgalla, G. I., Biffi, A. L. & Richeldi, L. U. C. A. Idiopathic pulmonary fibrosis : Diagnosis , epidemiology and. 427–437 (2016). doi:10.1111/resp.12683
  5. Barratt, S. L., Creamer, A., Hayton, C. & Chaudhuri, N. Idiopathic Pulmonary Fibrosis ( IPF ): An Overview. 1–21 (2018). doi:10.3390/jcm7080201

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Rare Disease Highlight: Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a blood cancer in which blast cells (immature myeloid precursor cells) multiply uncontrollably within the bone marrow and blood.1 The accumulation of blast cells disrupts normal blood cell production in the bone marrow as well as blood distribution to the tissues. This disruption leads to symptoms such as chronic fatigue, anemia, a compromised immune system, and high risk of hemorrhage.4,5 In addition, the current treatments for AML can cause many additional side effects due to drug toxicity.6-8 As these combined effects are severe, AML patients have low overall survival despite treatment and can still relapse after recovery is observed.2,3 According to the Surveillance, Epidemiology, and End Results (SEER) program, there were 19,520 new cases of AML in the US in 2018, with a reported 5-year survival rate of 27.4%.9  Risk factors associated with AML include age, history of blood disease, and/or genetic disorders.2,3 Thus, an unmet need exists for AML therapies which are non-invasive, non-toxic, and do not result in relapse.

References used
  1. Spivak JL. Acute Myelogenous Leukemia (AML). Merck Manual 2017; http://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/acute-myelogenous-leukemia-aml. Accessed November 20, 2017, 2017.
  2. Pui C-H, Carroll WL, Meshinchi S, Arceci RJ. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update. J Clin Oncol. 2011;29(5):551-565.
  3. PDQ PTEB. Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®). 2017.
  4. Cheng MJ, Hourigan CS, Smith TJ. Adult Acute Myeloid Leukemia Long-term Survivors. Journal of leukemia (Los Angeles, Calif). 2014;2(2):26855.
  5. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-474.
  6. Lipshultz SE, Sallan SE. Cardiovascular abnormalities in long-term survivors of childhood malignancy. J Clin Oncol. 1993;11(7):1199-1203.
  7. Volkova M, Russell R. Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment. Curr Cardiol Rev. 2011;7(4):214-220.
  8. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710-717.
  9. SEER. Cancer Stat Facts: Leukemia – Acute Myeloid Leukemia (AML). 2018; https://seer.cancer.gov/statfacts/html/amyl.html.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Rare Disease Highlight: Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a genetic disease which affects the part of the nervous system controlling voluntary muscle movement.1 SMA is the most common cause of mortality in infants associated with a genetic mutation. It affects approximately 1 in 6,000 to 10,000 people.2 Patients with SMA develop progressive muscle weakness caused by the loss of specialized nerve cells called motor neurons in the spinal cord and the brain stem. The symptoms of SMA cover a broad spectrum of severity based on the age at disease onset and motor ability.3 The most common form of SMA (accounting for 95% of all cases) is associated with mutations in the survival motor neuron 1 (SMN1) gene which lead to SMN1 protein deficiency and eventual loss of motor neurons.4 Currently there is no cure for this serious and life-threatening disease. While there are treatments to help manage the condition, the development of new SMA therapies are necessary to address longstanding unmet needs.5

References used
  1. Faravelli, I., Nizzardo, M., Comi, G., & Corti, S. (2015). Spinal muscular atrophy—recent therapeutic advances for an old challenge. Nature Reviews Neurology, 11(6), 351-359. doi: 10.1038/nrneurol.2015.77
  2. Pearn, J. (1978). Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. Journal Of Medical Genetics, 15(6), 409-413. doi: 10.1136/jmg.15.6.409
  3. Russman, B. (2007). Spinal Muscular Atrophy: Clinical Classification and Disease Heterogeneity. Journal Of Child Neurology, 22(8), 946-951. doi: 10.1177/0883073807305673
  4. Kolb, S. (2011). Spinal Muscular Atrophy. Archives Of Neurology, 68(8), 979. doi: 10.1001/archneurol.2011.74
  5. Spinal Muscular Atrophy Treatment – SMA News Today. (2019). Retrieved from https://smanewstoday.com/spinal-muscular-atrophy-treatment

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

Rare Disease Highlight: Hepatocellular Carcinoma (Liver Cancer)

Hepatocellular Carcinoma is a form of liver cancer associated with various stages of malignant growth in the liver. It is the sixth most common cancer worldwide, but is rare in the United States, only affecting around 60,000 patients.1,2 Hepatocellular carcinoma is considered a deadly cancer, with a survival rate of only 12.2% for five years, and the third major leading cause of cancer-related deaths worldwide.3,4 While most liver cancers are preventable, the incidence of hepatocellular has been increasing in the United States. This is possibly due to the frequency of common risk factors such as chronic liver disease, viral liver infections such as hepatitis, and liver cirrhosis.3,5 Hepatocellular carcinoma can be treated with standard of care therapies. Unfortunately, many patients with the disease have a high risk of developing resistance creating an unmet need for new treatment options of this serious and life-threatening disease.6

References used
  1. SEER Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. NCI; 2018. https://seer.cancer.gov/statfacts/html/livibd.html. Accessed 03/15/2018.
  2. Zhu RX, Seto WK, Lai CL, Yuen MF. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region. Gut Liver. 2016;10(3):332-339.
  3. Momin BR, Pinheiro PS, Carreira H, Li C, Weir HK. Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017;123 Suppl 24:5059-5078.
  4. Zhu YJ, Zheng B, Wang HY, Chen L. New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacol Sin. 2017;38(5):614-622.
  5. Kamarajah SK. Fibrosis score impacts survival following resection for hepatocellular carcinoma (HCC): A Surveillance, End Results and Epidemiology (SEER) database analysis. Asian Journal of Surgery. 2018;1(1)
  6. Pan S, Li Z, He Z, Qiu J, Zhou S. Molecular Mechanisms for Tumor Resistance to Chemotherapy. Clinical and Experimental Pharmacology and Physiology. 2016;2016(43):723-73

BioPharma Global is a not for profit-operating regulatory affairs firm specializing in FDA and EMA expedited designations for companies working to treat rare diseases. If you are a rare disease drug developer seeking Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, or other FDA/EMA designations, or if you are seeking pre-IND meeting assistance (type A, B, or C), the BioPharma Global regulatory team can help. Contact us today to arrange a 30-minute introductory call.