Rare Disease Highlight: Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a rare degenerative disease affecting neuromuscular abilities (Asher et al., 2020; Baker, 2017; Crisafulli et al., 2020). DMD is linked to the X-chromosome, meaning it primarily affects males, while females act as carriers of the disease (Baiardini et al., 2011; Crisafulli et al., 2020; Sussman, 2002). DMD affects approximately 1 in every 3,500 newborn boys in the US (NORD, 2016). The cause of DMD is a mutation in the dystrophin gene (NORD, 2016). This gene is responsible for the production of the dystrophin protein, a structural protein needed for stabilization and maintenance of the myofibers in the membrane of muscle cells, which is vital for muscle growth (Dalakas, 2017). The absence of dystrophin results in muscle degeneration, inflammation, and fibrosis, leading to the loss of skeletal muscle mass, which is replaced by fibrous and fatty tissue (Rugowska et al., 2021; Sussman, 2002).

Symptoms of DMD become apparent in early childhood when there are delays in reaching developmental milestones (Asher et al., 2020; NORD, 2016). Children present muscle weakness, spinal deformities, a waddling manner of walking, abnormal standing posture, loss of ambulation, and clumsiness (Baiardini et al., 2011; Birnkrant et al., 2018; Dalakas, 2017; Sussman, 2002). Additionally, DMD patients have difficulty walking, running, climbing stairs, jumping, and getting up from the floor (known as Gower’s sign) (Birnkrant et al., 2018; Crisafulli et al., 2020; Rugowska et al., 2021; Sussman, 2002). In addition to physical symptoms, patients with DMD can also exhibit cognitive and behavioral complications, such as intellectual disabilities, attention deficit hyperactivity disorder (ADHD), and disorders within the autism spectrum (Bylo et al., 2020; Crisafulli et al., 2020). Patients with DMD decline over time, eventually becoming completely physically dependent (Asher et al., 2020). During the teenage years, spinal deformities become evident, typically in the form of scoliosis or progressive curvature of the spine, and life-threatening cardiorespiratory conditions appear. The life expectancy of DMD patients is significantly reduced with mean age of deaths between the early 20s and the early 30s mainly due to cardiac and respiratory failures (Asher et al., 2020; Baker, 2017; Ryder et al., 2017; Sussman, 2002).

DMD is a fatal disease with no curative treatment. Patients are treated with palliative therapies to delay the severe problems associated with the disease, including a combination of physical rehabilitation, speech and language therapy, pain management, and surgery (NORD, 2016; Sussman, 2002). Commonly, DMD patients are treated with corticosteroids, which can improve muscle strength and delay disease progression. However, corticosteroids can have serious side effects and impact patients’ quality of life (Bylo et al., 2020; Sussman, 2002). More recently, the use of gene therapies to treat DMD at its root have been developed. These therapies are important advances in the treatment of DMD, but they are limited to a small number of patients depending on their specific genetic mutation (Baker, 2017; Birnkrant et al., 2018; Dalakas, 2017; NORD, 2016; Sussman, 2002). The development of novel therapies and treatments for DMD, and their subsequent approval by FDA, is essential to address this unmet medical need and improve the lives of all people affected by this disease.

References used:

  • Asher, D. R., Thapa, K., Dharia, S. D., Khan, N., Potter, R. A., Rodino-Klapac, L. R., & Mendell, J. R. (2020). Clinical development on the frontier: gene therapy for duchenne muscular dystrophy. Expert Opinion on Biological Therapy, 20(3), 263-274. doi:10.1080/14712598.2020.1725469
  • Baiardini, I., Minetti, C., Bonifacino, S., Porcu, A., Klersy, C., Petralia, P., . . . Braido, F. (2011). Quality of life in Duchenne muscular dystrophy: the subjective impact on children and parents. J Child Neurol, 26(6), 707-713. doi:10.1177/0883073810389043
  • Baker, D. E. (2017). Eteplirsen. Hosp Pharm, 52(4), 302-305. doi:10.1310/hpj5204-302
  • Birnkrant, D. J., Bushby, K., Bann, C. M., Apkon, S. D., Blackwell, A., Brumbaugh, D., . . . Weber, D. R. (2018). Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol, 17(3), 251-267. doi:10.1016/s1474-4422(18)30024-3
  • Bylo, M., Farewell, R., Coppenrath, V. A., & Yogaratnam, D. (2020). A Review of Deflazacort for Patients With Duchenne Muscular Dystrophy. Ann Pharmacother, 54(8), 788-794. doi:10.1177/1060028019900500
  • Crisafulli, S., Sultana, J., Fontana, A., Salvo, F., Messina, S., & Trifirò, G. (2020). Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet Journal of Rare Diseases, 15(1), 141. doi:10.1186/s13023-020-01430-8
  • Dalakas, M. C. (2017). Gene therapy for Duchenne muscular dystrophy: balancing good science, marginal efficacy, high emotions and excessive cost. Ther Adv Neurol Disord, 10(8), 293-296. doi:10.1177/1756285617717155
  • NORD. (2016). Duchenne Muscular Dystrophy. Retrieved March 3, 2022 from https://rarediseases.org/rare-diseases/duchenne-muscular-dystrophy/
  • Rugowska, A., Starosta, A., & Konieczny, P. (2021). Epigenetic modifications in muscle regeneration and progression of Duchenne muscular dystrophy. Clin Epigenetics, 13(1), 13. doi:10.1186/s13148-021-01001-z
  • Ryder, S., Leadley, R. M., Armstrong, N., Westwood, M., de Kock, S., Butt, T., . . . Kleijnen, J. (2017). The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet Journal of Rare Diseases, 12(1), 79. doi:10.1186/s13023-017-0631-3
  • Sussman, M. (2002). Duchenne muscular dystrophy. J Am Acad Orthop Surg, 10(2), 138-151. doi:10.5435/00124635-200203000-00009

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a unmet medical needs. 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.

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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.