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group_3_presentation_1_-_al_amyloidosis [2017/10/06 23:22] rajendaa |
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| ====== Social Implications ====== | ====== Social Implications ====== | ||
| - | AL Amyloidosis or Amyloidosis in general is a disease not known by the majority of society. Among those who do there are often a lot of misconceptions and wrongful information. A lot is being done by corporations/foundations in order to spread correct information about the disease to the general public in order to create awareness. The Amyloidosis Foundation is one such foundation looking to create awareness, collect donation for patients and invest in research that will go a long in helping those affected by the disease. | + | AL Amyloidosis or Amyloidosis in general is a disease not very known by the majority of society. Among those who do know of the disease, there are often a lot of misconceptions or incorrect understanding of the scientific information. However, a lot is being done by corporations and foundations in order to spread correct information about the disease to the general public in order to create awareness. |
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| + | The Amyloidosis Foundation is one such foundation. According to their website, they were created by the merging of the Amyloidosis Research Foundation and the Amyloidosis Support Network in 2007 ("Us - Amyloidosis Foundation", n.d.). Some of the goals of the foundation is that they are looking to create awareness, collect donation for patients, and invest in research that will go a long way in helping those affected by the disease. As can be seen on the website, they also have many inspirational stories of former patients who have gone through having the AL Amyloidosis disease ("Us - Amyloidosis Foundation", n.d.). This is a fantastic resource for patients that have recently discovered they have AL Amyloidosis as they may feel they are all alone. However, on the contrary, this is not the case and in fact through reading the stories on the website, they can see there are many other people in the same situation as them. Thus, the foundation's stories of other patients acts as a sort of moral encouragement for new patients. Finally, the foundation also provides updates on the latest news regarding AL Amyloidosis research, among other things. This too acts as a great resource for patients as not all of them will have the technical knowledge to read the actual scientific research articles. Instead, they can read an adapted and summarized version presented on the foundation's news website. This still allows them to feel in the know about the current state of research into discovering a cure for this devastating disease. Overall, the foundation acts as a bridge to connect patients with resources to help them better overcome their disease and to live a happier, fuller life. | ||
| ====== Further Research / Applications ====== | ====== Further Research / Applications ====== | ||
| - | There is still a lot of research that needs to be done on AL Amyloidosis in order successfully diagnose and treat everyone who happens to obtain the disease with a high rate of success. The research being conducted spans a variety of platforms such as alternate treatments, enhancements to current treatments, earlier diagnosis methods and prevention methods. Of all such platforms the focus is on discovering tools in which to diagnose patients earlier even before the appearance of symptoms in order to apply treatment earlier which helps increase success and survivor-ship. | + | There is still a lot of research that needs to be done on AL Amyloidosis in order to successfully diagnose and treat everyone who gets diagnosed. The research being conducted spans a variety of platforms such as alternate treatments, enhancements to current treatments, earlier diagnosis methods and prevention methods. The focus is on discovering tools through which diagnosis can be made earlier, even before the appearance of symptoms, in order to provide treatment earlier and to help increase success and survivor-ship. |
| ==== Epigallocatechin-3-Gallate (EGCG): ==== | ==== Epigallocatechin-3-Gallate (EGCG): ==== | ||
| - | Epigallocatechin-3-Gallate (EGCG) is being looked at as a potential treatment for AL Amyloidosis. EGCC is the most abundant catechin in tea. EGCC is studied greatly today for its potential effects on human health and diseases. It is used in many dietary supplements. It is found in high concentrations in the dried leaves of green tea, white tea and black tea (Andrich et al., 2016). Trace amounts are found in foods such as apple skins, plums, onions and pecans (Andrich et al., 2016). EGCC is currently the subject of pre-clinical studies involving autoimmune diseases, inflammation and rheumatoid arthritis (Andrich et al., 2016). Recently, EGCC is being looked at as a secondary treatment for AL Amyloidosis. Research so far has suggested that EGCG specifically inhibits the second aggregation phase causing the formation of more stable non-amyloid light chain aggregates (Andrich et al., 2016). Scientists are most intrigued by the fact that EGCG intervention does not depend on the individual sequences of the light chains and thus can potentially be universally used as a treatment (Andrich et al., 2016). Further research is required in order to determine if EGCG would work at larger quantities and if it sustain inhibition for a prolonged period of time. | + | Epigallocatechin-3-Gallate (EGCG) is being looked at as a potential treatment for AL Amyloidosis. EGCC is the most abundant catechin in tea. EGCC is studied greatly today for its potential effects on human health and diseases. It is used in many dietary supplements. It is found in high concentrations in the dried leaves of green tea, white tea and black tea (Andrich et al., 2016). Trace amounts are found in foods such as apple skins, plums, onions and pecans (Andrich et al., 2016). EGCC is currently the subject of pre-clinical studies involving autoimmune diseases, inflammation and rheumatoid arthritis (Andrich et al., 2016). Recently, EGCC is being looked at as a secondary treatment for AL Amyloidosis. Research so far has suggested that EGCG specifically inhibits the second aggregation phase causing the formation of more stable non-amyloid light chain aggregates (Andrich et al., 2016). Scientists are most intrigued by the fact that EGCG intervention does not depend on the individual sequences of the light chains and thus can potentially be universally used as a treatment (Andrich et al., 2016). Further research is required in order to determine if EGCG would work at larger quantities and if it sustains inhibition for a prolonged period of time. |
| <box width classes blue centre|http://toptestosteronesupplements.com/epigallocatechin-gallate-egcg-ingredient-breakdown/>{{ epigallocatechin-gallate-egcg-2_top-testosterone-supplement.jpg?nolink&200 }}</box|Figure 8: Molecular structure of EGCG. EGCG found commonly in a variety of dried tea leaves. Looked at as a potential treatment for AL Amyloidosis.> | <box width classes blue centre|http://toptestosteronesupplements.com/epigallocatechin-gallate-egcg-ingredient-breakdown/>{{ epigallocatechin-gallate-egcg-2_top-testosterone-supplement.jpg?nolink&200 }}</box|Figure 8: Molecular structure of EGCG. EGCG found commonly in a variety of dried tea leaves. Looked at as a potential treatment for AL Amyloidosis.> | ||
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| ==== Monoclonal Antibodies - NEOD001: ==== | ==== Monoclonal Antibodies - NEOD001: ==== | ||
| - | The most cutting edge approach to AL Amyloidosis is the use of monoclonal antibodies which would clear the amyloid from the affected organs. Recent studies looking at NEOD001 have been very promising. NEOD001 is a monoclonal antibody that specifically targets the aggregated amyloid that accumulates in AL patients which would be eliminated (Gertz et al., 2016). In one study 69 patients were administrated NEOD001 post chemotherapy (Gertz et al., 2016). Response rate was 53% in cardiac patients and 64% among renal patients with little to no adverse side-effects (Gertz et al., 2016). NEOD001 also demonstrated improved neuro-pathy (Gertz et al., 2016). There are high hopes for this treatment and is currently in phase 2 of pre-clinical trials with phases 3 study planned. | + | The most cutting-edge approach to AL Amyloidosis is the use of monoclonal antibodies which would clear the amyloid from the affected organs. Recent studies looking at NEOD001 have been very promising. NEOD001 is a monoclonal antibody that specifically targets and eliminates the aggregated amyloid that accumulates in AL patients(Gertz et al., 2016). In one study, 69 patients were administrated NEOD001 post-chemotherapy (Gertz et al., 2016). Response rate was 53% in cardiac patients and 64% among renal patients with little to no adverse side-effects (Gertz et al., 2016). NEOD001 also demonstrated improved neuropathy (Gertz et al., 2016). There are high hopes for this treatment and it is currently in phase two of pre-clinical trials with phases 3 study planned. |
| ==== Genetically Engineered Cells: ==== | ==== Genetically Engineered Cells: ==== | ||
| - | Pre-Clinical testing is un-going on a potential treatment for AL Amyloidosis where a patient’s own immune system is genetically engineered to recognize and kill abnormal blood cells when reintroduced into the body (Rosenzweig, M., 2017). The goal of the research currently is to evaluate blood cells of patients with AL Amyloidosis and to find a specific protein that could be targeted (Rosenzweig, M., 2017). This protein must be unique to infected blood cells of AL Amyloidosis patients. Once this key step is completed in laboratory testing of genetically engineered cells be able to occur. | + | Pre-Clinical testing is on-going on a potential treatment for AL Amyloidosis where a patient’s own immune system is genetically engineered to recognize and kill abnormal blood cells when reintroduced into the body (Rosenzweig, M., 2017). The current goal of the research is to evaluate blood cells of patients with AL Amyloidosis and to find a specific protein that could be targeted (Rosenzweig, M., 2017). This protein must be unique to the infected blood cells of AL Amyloidosis patients. Once this key step is completed, in-laboratory testing of genetically engineered cells will occur. |
| ==== Study of Gene Expression Changes/Mutations: ==== | ==== Study of Gene Expression Changes/Mutations: ==== | ||
| - | To date, mutations/proteins involved in AL Amyloidosis are poorly understood and the lack of knowledge is holding back scientists from studying a broader range of treatments as well as being able to diagnose patients much earlier in life. A large portion of scientific research on AL Amyloidosis is spent on understanding and locating varies proteins, mutations and gene expressions that play a role in the diseases rise (Zhou et al., 2012). Identifying and understanding such aspects not only helps with further treatment development but also helps diagnosis patients early in the disease stage or ideally before symptoms even take place. A large-scale characterization of the mutations and gene expression changes that occur when developing AL Amyloidosis is currently occurring (Zhou et al., 2012). | + | To date, mutations/proteins involved in AL Amyloidosis are poorly understood and the lack of knowledge is holding back scientists from studying a broader range of treatments as well as being able to diagnose patients much earlier in life. A large portion of scientific research on AL Amyloidosis is spent on understanding and locating varies proteins, mutations and gene expressions that play a role in the development of this disease (Zhou et al., 2012). Identifying and understanding such aspects not only helps with further treatment development but also helps diagnosis patients early in the disease stage or ideally before symptoms even occur. A large-scale characterization of the mutations and gene expression changes that occur when developing AL Amyloidosis is currently occurring (Zhou et al., 2012). |
| ==== Clear Amyloid Protein Deposits (Immunotherapy / Physical): ==== | ==== Clear Amyloid Protein Deposits (Immunotherapy / Physical): ==== | ||
| - | Clearing Amyloid protein deposits directly was seen as impossible but recent research has now proves this misconception incorrect. It has been discovered that some immune cells known as Scavenger Cells have the capabilities of engulfing and breaking apart Amyloid deposits (Rosenzweig et al., 2017). However, the production and effectiveness of such cells are not at the levels required to clear large deposits of amyloids (Rosenzweig et al., 2017). New immunotherapy treatments are trying to accelerate the productiona nd functionality of such immune cells in order to be able to clear larger deposits as well as clear them quicker (Rosenzweig et al., 2017). 3 of such immuno-therapies are currently in stage 3 of clinical trails. There is a lot of hope in this form of treatment due to it being both efficient and safe (Rosenzweig et al., 2017). | + | Clearing Amyloid protein deposits directly was previously seen as impossible but recent research has now proved this misconception incorrect. It has been discovered that immune cells known as Scavenger Cells, have the capabilities of engulfing and breaking apart Amyloid deposits (Rosenzweig et al., 2017). However, the production and effectiveness of such cells are not at the levels required to clear large deposits of amyloids (Rosenzweig et al., 2017). New immunotherapy treatments are trying to accelerate the production and functionality of such immune cells in order to be able to clear larger deposits as well as clear them quickly (Rosenzweig et al., 2017). Three of such immuno-therapies are currently in stage 3 of clinical trials. There is a lot of hope in this form of treatment due to it being both efficient, effective and safe (Rosenzweig et al., 2017). |
| - | Basic research has also begun on constructing machinery that can physically be inserted into the body, target amyloid deposits, break the amyloid deposits into smaller piece and finally remove all traces of the amyloid deposits (Rosenzweig et al., 2017). Constructing such machinery while ensuring the patients safety is not an easy task. Research into such machinery has only recently begun and is a ways away from being a realistic treatment method for AL Amyloidosis. | + | Basic research has also begun on constructing machinery that can physically be inserted into the body, target amyloid deposits, break the amyloid deposits into smaller piece and finally remove all traces of the amyloid deposits (Rosenzweig et al., 2017). Constructing such machinery while ensuring the patient's safety is not an easy task. Research into such machinery has only recently begun and is far away from being a realistic treatment method for AL Amyloidosis. |
| ==== Proteasome Inhibitors: ==== | ==== Proteasome Inhibitors: ==== | ||
| - | There are currently 2 drugs in clinical trails that specifically target proteasomes required in the formation of the amyloid aggregates (Sanchorawala et al., 2017). Inhibition of such prevents such proteasomes from doing their role of degrading specific proteins (Sanchorawala et al., 2017). The proteins they normally degrade are proteins that stop the aggregation and formation of amyloid fibrils. Thus the 2 drugs would keep the preventive proteins in tact and amyloid fibrils would be prevented from every forming (Sanchorawala et al., 2017). The two drugs carfilzomib and ixazomib are very close to market release. | + | There are currently 2 drugs in clinical trials that specifically target proteasomes required in the formation of the amyloid aggregates (Sanchorawala et al., 2017). Inhibition of such prevents such proteasomes from doing their role of degrading specific proteins (Sanchorawala et al., 2017). The proteins they normally degrade are proteins that stop the aggregation and formation of amyloid fibrils. Thus the 2 drugs would keep the preventive proteins intact and amyloid fibrils would be prevented from every forming (Sanchorawala et al., 2017). The two drugs carfilzomib and ixazomib are very close to market release. |
| ==== Other: ==== | ==== Other: ==== | ||
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| 2. **Targeting of SAP Protein:** Potential new drug treatments are targeting the SAP protein which is a very specific protein structure found exclusively on Amyloid deposits and no other human cells/structures. Targeting such a protein will prevent any harm being done on normal healthy cells (Wechaleka et al., 2016). | 2. **Targeting of SAP Protein:** Potential new drug treatments are targeting the SAP protein which is a very specific protein structure found exclusively on Amyloid deposits and no other human cells/structures. Targeting such a protein will prevent any harm being done on normal healthy cells (Wechaleka et al., 2016). | ||
| - | 3. **Vaccines:** The formation of a new vaccine is being studies that when administrated would protect vital organs such as the heart from Amyloid Formation. The basic idea is that such antibodies would coat and organs and prevent amyloid fibrils from attaching and growing (Sanchorawala et al., 2017). | + | 3. **Vaccines:** The formation of a new vaccine is being studied that when administrated would protect vital organs such as the heart from Amyloid Formation. The basic idea is that such antibodies would coat and organs and prevent amyloid fibrils from attaching and growing (Sanchorawala et al., 2017). |
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| - Tennent, G. A., Lovat, L. B., & Pepys, M. B. (1995). Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. //Proceedings of the National Academy of Sciences of the United States of America//, 92(10), 4299–4303. Received from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41931/pdf/pnas01486-0235.pdf | - Tennent, G. A., Lovat, L. B., & Pepys, M. B. (1995). Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. //Proceedings of the National Academy of Sciences of the United States of America//, 92(10), 4299–4303. Received from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41931/pdf/pnas01486-0235.pdf | ||
| - Tidy, C. (2014). Amyloidosis. Patient. Retrieved from: https://patient.info/doctor/amyloidosis-pro | - Tidy, C. (2014). Amyloidosis. Patient. Retrieved from: https://patient.info/doctor/amyloidosis-pro | ||
| + | - Us - Amyloidosis Foundation. Amyloidosis Foundation. Retrieved 7 October 2017, from http://www.amyloidosis.org/us/#our-history | ||
| - Wallick, S. C., Kabat, E. A., & Morrison, S. L. (1988). Glycosylation of a VH residue of a monoclonal antibody against alpha (1-6) dextran increases its affinity for antigen. //The Journal of Experimental Medicine//, 168(3), 1099–1109. . https://doi.org/10.1084/jem.168.3.1099 | - Wallick, S. C., Kabat, E. A., & Morrison, S. L. (1988). Glycosylation of a VH residue of a monoclonal antibody against alpha (1-6) dextran increases its affinity for antigen. //The Journal of Experimental Medicine//, 168(3), 1099–1109. . https://doi.org/10.1084/jem.168.3.1099 | ||
| - Warsame, R., Kumar, S. K., Gertz, M. A., Lacy, M. Q., Buadi, F. K., Hayman, S. R., … Dispenzieri, A. (2015). Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death. //Blood Cancer Journa//l, 5, 310. https://doi.org/10.1038/bcj.2015.34 | - Warsame, R., Kumar, S. K., Gertz, M. A., Lacy, M. Q., Buadi, F. K., Hayman, S. R., … Dispenzieri, A. (2015). Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death. //Blood Cancer Journa//l, 5, 310. https://doi.org/10.1038/bcj.2015.34 | ||
