question: Why is ALS impossible to cure?
comment: It’s not impossible — but there’s yet to be a truly successful treatment found. The disease is complex, and spreads as it progresses. The myelin sheath of nerves degrades, and as that happens, body systems start to have problems and then stop working. Think of myelin like the insulation on wiring, if the wiring in your house started to be degraded by the air around it — the damage would be widespread and difficult to fix without widespread and costly repairs. Body repairs like that would be difficult, _if_ it was easy to repair nerve damage. It would be difficult due to limited access to the nerves, alone. The fact that nerve damage is very difficult to repair — mostly impossible — is part of the problem. The fact that ALS is both a systemic disease and progressive complicate it, too.
passages: Most cases of ALS, however, are correctly diagnosed, with the error rate of diagnosis in large ALS clinics being less than 10%. One study examined 190 people who met the MND/ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these people (16%) had their diagnosis completely changed during the clinical observation development period. In the same study, three people had a false negative diagnosis of MG, which can mimic ALS and other neurological disorders, leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not.
  
  Section::::Management.
   In 2008, scientists from the Jenifer Estess Stem Cell Lab, Harvard, and Columbia achieved the "Time" "Scientific Breakthrough of the Year" by reprogramming motor neurons from a small sample of skin from an ALS patient — a method known as iPS, or induced pluripotent stem cell technology.
  
  Section::::Research.:Improving Cell Metabolism.
  
  A cell's inability to metabolize proteins is a hallmark of ALS, Alzheimer's, Parkinson's and Huntington's diseases. The Project ALS team led by researchers at Harvard and the University of Massachusetts are studying pathways responsible for poor protein management in ALS.
  
  Section::::Research.:Ocular Motor Neuron Resistance study.
   The first animal model for ALS was the "SOD1" transgenic mouse, which was developed in 1994. It expresses about 20–24 copies of the mutant human "SOD1" gene and reproduces most of the clinical and pathological findings seen in ALS. Although there are now over 20 different "SOD1" mouse models, the "SOD1" model remains both the most widely used "SOD1" mouse model and the most widely used ALS mouse model overall. Much of the present understanding of ALS pathophysiology came from studying mouse models that overexpress mutant "SOD1", especially "SOD1" mice. However, many drug targets that were shown to be effective in the "SOD1" transgenic mouse failed in clinical trials in humans; other "SOD1" models have had similar problems. Most of these drugs were identified as potentially effective based on a single study in a rodent "SOD1" model and then failed in clinical trials in patients who primarily had sporadic ALS. It is thought that these clinical trials failed because "SOD1" mutations account for only 2% of all ALS cases and because the pathology of "SOD1" ALS is thought to be distinct from all other types of ALS; it lacks the abnormal aggregations of TDP-43 protein and/or FUS protein seen in nearly all other cases of ALS.
   A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), Lyme disease, and syphilis. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy, and spinal and bulbar muscular atrophy can also mimic certain aspects of the disease and should be considered.
   Section::::Research.
  
  Section::::Research.:Model organisms.
  
  Many different organisms are used as models for studying ALS, including "Saccharomyces cerevisiae" (a species of yeast), "Caenorhabditis elegans" (a roundworm), "Drosophila melanogaster" (the common fruit fly), "Danio rerio" (the zebrafish), "Mus musculus" (the house mouse), and "Rattus norvegicus" (the common rat). None of these models perfectly represents ALS in humans, partly because most animal models are based on gene overexpression, meaning that multiple copies of the mutant human gene are inserted into the transgenic model, and partly because the human nervous system is very different from that of other animals.
   Non-invasive ventilation (NIV) is the main treatment for respiratory failure in ALS. In people with normal bulbar function, it prolongs survival by about seven months and improves quality of life. One study found that NIV is ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression and functional decline continue. It may decrease the quality of life of people with ALS and/or their caregivers. Invasive ventilation is more commonly used in Japan than North America or Europe.
   Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die between two and four years after the diagnosis. Around half of people with ALS die within 30 months of their symptoms beginning, and about 20% of people with ALS live between five and 10 years after symptoms begin. Guitarist Jason Becker has lived since 1989 with the disorder, while cosmologist Stephen Hawking lived for 55 more years following his diagnosis, but they are considered unusual cases.
   Techniques to deliver drugs and medications in a better manner are also being investigated and those include altering and developing drugs with specific characteristics, such as size and charge, to allow for their passage through the blood-brain barrier. Furthermore, specific antisense oligonucleotides are being developed that may slow down the progression of ALS and reduce toxicity. Antisense oligonucleotides target specific sequences associated with the C9ORF72 gene that has been identified as a cause for ALS. Another delivery technique being investigated is through adeno-associated viruses that have the ability to deliver drugs and other proteins and genetic components to the central nervous system and aid in protecting neurons from damage caused by ALS.
   In 2006, it was discovered that the protein TDP-43 is a major component of the inclusion bodies seen in both ALS and frontotemporal dementia (FTD), which provided evidence that ALS and FTD are part of a common disease spectrum. This led to the discovery in 2008 that mutations in "TARDBP", the gene that codes for TDP-43, are a cause of familial ALS. In 2011, noncoding repeat expansions in "C9orf72" were found to be a major cause of ALS and FTD. Edaravone was approved to treat ALS in Japan and South Korea in 2015 and in the United States in 2017. , it has not been approved to treat ALS in Europe.
   BULLET::::- 2) Patients with PMA do not suffer from the cognitive change identified in certain groups of patients with MND.
  
  BULLET::::- 3) Because PMA patients do not have UMN signs, they usually do not meet the "World Federation of Neurology El Escorial Research Criteria" for “Definite” or “Probable” ALS and so are ineligible to participate in the majority of clinical research trials such as drugs trials or brain scans.
   The current results are published in the November 25 issue of Neurology. The researchers were led by Eric J. Sorenson, MD, from the Mayo Clinic in Rochester, Minnesota ""While this is very disappointing, at least it was definitive and gives, I think, a pretty definitive answer, at least for this strategy for this drug,"" Dr. Sorenson said. However, he added, ""there is still a great deal of evidence that the IGF-1 pathway can be beneficial to people who have ALS, but just not the way we administered it.""
   No cure for ALS is known. The goal of treatment is to improve symptoms. A medication called riluzole may extend life by about two to three months. Non-invasive ventilation may result in both improved quality and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help. The disease can affect people of any age, but usually starts around the age of 60 and in inherited cases around the age of 50. The average survival from onset to death is two to four years, though this can vary. About 10% survive longer than 10 years. Most die from respiratory failure. In Europe, the disease affects about two to three people per 100,000 per year. Rates in much of the world are unclear. In the United States, it is more common in white people than black people.
   There is no cure for Alström syndrome. Treatments target the individual symptoms and can include diet, corrective lenses, hearing aids, medications for diabetes and heart issues and dialysis and transplantation in the case of kidney or liver failure. Prognosis varies depending on the specific combination of symptoms, but individuals with Alström syndrome rarely live beyond 50.
   ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, people with ALS symptoms should always obtain a specialist neurological opinion in order to rule out alternative diagnoses. Myasthenic syndrome, also known as Lambert–Eaton syndrome, can mimic ALS, and its initial presentation can be similar to that of myasthenia gravis (MG), a treatable autoimmune disease sometimes mistaken for ALS. Benign fasciculation syndrome is another condition that mimics some of the early symptoms of ALS, but is accompanied by normal EMG readings and no major disablement.
   Repetitive transcranial magnetic stimulation had been studied in amyotrophic lateral sclerosis in small and poorly designed clinical trials; as of 2013, there was insufficient evidence to know whether rTMS is safe or effective for ALS.
   On July 25, 2016, the ALS Association announced that, thanks in part to donations from the Ice Bucket Challenge, the University of Massachusetts Medical School has identified a third gene that is a cause for the disease. Project MinE, a global gene sequencing effort to identify genetic drivers of ALS, received $1 million from the challenge, allowing them to broaden the scope of their research to include new sources in new parts of the world. Having identified the link between the gene, NEK1, and ALS will allow for a new targeted gene for therapy development, as well as focused drug development.
   Pain is a symptom experienced by most people with ALS and can take the form of neuropathic pain (pain caused by nerve damage), spasticity, muscle cramps, and nociceptive pain caused by reduced mobility and muscle weakness; examples of nociceptive pain in ALS include contractures (permanent shortening of a muscle or joint), neck pain, back pain, shoulder pain, and pressure ulcers.
  
  Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.
  
  Section::::Signs and symptoms.:Initial symptoms.
   Primary lateral sclerosis (PLS) accounts for about 5% of all cases of ALS and affects upper motor neurons in the arms and legs. However, more than 75% of people with apparent PLS develop lower motor neuron signs within four years of symptom onset, meaning that a definite diagnosis of PLS cannot be made until then. PLS has a better prognosis than classic ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss.
   In 2018, ALS TDI was the original beneficiary of the ALS Pepper Challenge, where participants eat a chili pepper. Various public figures, including Kelly Clarkson, Jimmy Kimmel, Shaquille O'Neal, Nancy O'Dell, Wolf Blitzer, the Miami Heat and Andy Cohen have participated in the challenge.
  
  Section::::Research.
   ALS affects nearly all voluntary muscles in the body except for the muscles controlling eye movement. Project ALS is driving a six-laboratory study of ocular motor neuron resistance. The goal is to confer resistance upon more vulnerable motor neurons in ALS.
  
  Section::::Research.:Lipids.
  
  Project ALS researchers at Columbia University have identified distinctive lipid signatures that may lead to early diagnosis and information about disease progression.
  
  Section::::Celebrity involvement.
  
  The following people and groups have been involved with Project ALS:
  
  BULLET::::- Julianna Margulies
  
  BULLET::::- Anne Meara
  
  BULLET::::- Caroline Rhea
  
  BULLET::::- Debora Spar
  
  BULLET::::- Thomas Jessel
  
  BULLET::::- Northport High School
  
  BULLET::::- Donna Hanover
   In early 2018, a patient group called the "Terminally Persistent" coalition criticized the ALS Association for not spending the $115 million earned from the Ice Bucket Challenge more readily on research. Additionally, the group complained that the organization was not funding Phase III clinical trials for Brainstorm Cell Therapeutics, a pharmaceutical company researching treatments for ALS. In a blog post, the Association said that they don't and never have funded Phase III trials, though, according to their website, they did in 2015 with Cytokinetics.
   The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies (abnormal aggregations of protein) in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is TDP-43 protein; however, in those with "SOD1" or "FUS" mutations, the main component is SOD1 protein or FUS protein, respectively. The gross pathology of ALS, which are features of the disease that can be seen with the naked eye, include skeletal muscle atrophy, motor cortex atrophy, sclerosis of the corticospinal and corticobulbar tracts, thinning of the hypoglossal nerves (which control the tongue), and thinning of the anterior roots of the spinal cord. Besides for the death of motor neurons, two other characteristics common to most ALS variants are focal initial pathology, meaning that symptoms start in a single spinal cord region, and progressive continuous spread, meaning that symptoms spread to additional regions over time. Prion-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others.
   Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
   Essey Prize for ALS Research, The ALS Association, 2014
  
  UCSD Chancellor's Award for Excellence in Postdoctoral Scholar Mentoring, 2014
  
  Thomas Reuters' 2015 listing of "The World's Most Influential Scientific Minds" 2015
  
  Breakthrough Prize in Life Sciences, 2018 
  
  NOMIS Distinguished Scientist Awardee,2018
  
  Section::::External links.
  
  BULLET::::- ASCB 2013 – Saturday, December 14th President's Introduction 
  
  BULLET::::- UCSD and Ludwig Cancer Research Ice Bucket Challenge
  
  BULLET::::- Clive Svendsen and Don W. Cleveland "Ask The Experts" 
  
  BULLET::::- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale
  
  BULLET::::- 2014 "Commitment to a Cure" Essey Award Winners Newsreel
   BULLET::::- Valproic scid: Valproic acid in mice studies restored histone acetylation levels, increased levels of pro-survival factors, and mice showed improved motor performance. However, while the drug delayed the onset of ALS, it did not increase lifespan or prevent denervation. Human trials of valproic acid in ALS patients did not improve survival or slow progression.
  
  BULLET::::- Trichostatin A: Trichostatin A trials in mouse ALS models restored histone acetylation in spinal neurons, decreased axon demyelination, and increased survival of mice.
  
  Section::::Neurodegenerative diseases of motor neurons.:Spinal Muscular Atrophy (SMA).
  
presuppositions: ALS is impossible to cure. ALS is impossible to cure.
corrections: ALS is not impossible to cure pending for a truly successful treatment to be found. ALS is not impossible to cure but there hasn't been a development of a successful treatment yet.
raw_presuppositions: ALS is impossible to cure. ALS is impossible to cure.
raw_corrections: ALS is not impossible to cure pending for a truly successful treatment to be found. ALS is not impossible to cure but there hasn't been a development of a successful treatment yet.