What is Pompe Disease? What does it look like? http://www.fightpompe.com/about/21/about-juan
Symptoms • Early onset • Cardiac and respiratory infections/failure • Other difficulties: Floppiness, inability to gain weight • Death (within 1 year) • Late onset • Skeletal and joint muscles • Difficulty breathing
Genetic Basis of Pompe Disease • Pompe disease is caused by a variety of mutations that occur on the GAA gene (alpha-glucosidase) located on chromosome 17. The wildtype function of alpha-glucosidaseis to cleave alpha glycosidic linkages between glucose and glycogen. This provides the cell with usable glucose. • Mutations in the gene cause the protein to malfunction, causing decreased or completely eliminated activity. Without functioning alpha glucosidase, glycogen builds up in the cells. Overtime, this buildup prevents proper movement and function of muscles.
Optimal Treatment • Myozyme was the first drug developed and is injected intravenously into pompe patients. However, this can often be a frustrating process as the treatment is not a cure and the patients must visit the hospital many times per year. For children, this can heavily interfere with their schoolwork and their self-confidence.
Myozyme • “Myozyme(alglucosidasealfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency). Myozymehas been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.” • Problems • Infusion reactions occurred in 20 of 39 (51%) of patients treated with MYOZYME in clinical studies • Most patients who develop antibodies do so within the first 3 months of exposure
Reasons for further research… Not 100% effective Cost
Main Idea: Reverse Pompe disease before birth through genetic manipulation • Modeled after induced pluripotent stem cells (iPSC) Research Goal
Also similar to sickle cell anemia studies • Mice models would be used in early stages of research, with human embryonic cells used in the future if research looks promising for potential medical applications
Outline of Potential Research • Steps for Research • Proteins are introduced into infected cells. • These proteins cleave gene at specific loci. • Wild-type gene is inserted at cleaved loci. • Cells with the corrected mutation are re-introduced into the organism.
Three Main Policy Goals: 1) Lifting Restriction of Research 2) Funding Research 3) Educating the Public and Encouraging Genetic Testing
Lifting Restriction of Research: • This goal relates specifically to our research question. We would focus on altering the current restrictions on embryonic research. • Many scientists currently write about the ethical concerns of using embryonic stem cells. The general consensus is usually that human embryos are not conscious and in this way it is no more unethical to work on these embryos than on mice.
Funding Research: • The government should not only lift its restrictions, but also help fund the research or at least promote the research in a positive light so other organizations will fund it. • In addition, the government does not need to fund embryonic research per-say, but research to improve enzyme replacement therapy for example. • Even though this requires money, medicine will never progress if we do not invest money into medical/scientific research. We just need to be smart about investing in the area that looks most promising.
Educating the Public and Encouraging Genetic Testing: • The public (especially couples who are considering having children) need to educated about Pompe Disease by their physicians. • Part of the education process is to let them know about genetic testing for Pompe Disease and encourage couples who may have high risk of being carriers to get themselves tested. • This will let couples know if they are actual carriers of the mutant allele, which will allow them to make a more informed decision, whether it is getting their child tested, or preparing themselves for facing the disease in the future (if they happen to have it).