News Article | September 7, 2016
In 1996, Kathy Giusti was diagnosed with multiple myeloma, a rare and often fatal cancer. Her first bone-marrow biopsy took place on a Friday night. Outside the room, a group of scientists waited with an ice chest to take her bone-marrow sample. She told her doctor that she was surprised to see them working late. “He said my tissue was precious,” she recalls. For precision medicine to live up to its potential, millions of people must share their genomic data, their health records, and their experiences. To researchers, all of it is precious. The richer the databases, the better patient care will become. This need gives ordinary people more power in medical research — not only to improve research quality by participating in greater numbers, but by speaking up and influencing what questions are asked in the first place. Despite lingering concerns over privacy (see page S70), it is patients and their loved ones who have been pushing for changes to the medical system that will enable personalized medicine, says Guisti, who founded the Multiple Myeloma Research Foundation with her sister in 1998. For individual patients, empowerment takes a lot of time, work, education and economic resources. If programmes such as the United States' planned million-volunteer Precision Medicine Initiative Cohort Program are to succeed (see page S69), they must build people's trust and bring in not only highly motivated, seriously ill people, but healthy volunteers too. Early patient-centred research projects are already showing that this can pay off for researchers, for drug companies and, more importantly, for patients. It can be difficult for even well-educated, financially secure people living close to major US medical centres to access the best medical care. In 1998, Marty Tenenbaum was diagnosed with melanoma that had metastasized to his liver, “which in those days had zero survivors”, he says. After a lot of searching, he was lucky enough not just to get onto a trial for an experimental therapy and surgery, but to be one of the few who responded. The trial failed, but Tenenbaum is still in remission. This experience, and the genome-sequencing boom, led Tenenbaum — a computer scientist and former professor at Stanford University — to found a personalized-medicine consultancy called CollabRX in 2008. The company used bioinformatics to suggest therapies to its wealthy customers at a cost of US$35,000–50,000. “My vision was to use information technology to close the loop between cancer research and clinical care,” he says. When CollabRX was acquired by Tegal in 2012, Tenenbaum wanted to start a non-profit organization that could serve more people. So he set up Cancer Commons, whose goal is to make the expertise of the best clinicians available to more cancer patients — especially those who cannot afford to travel to the best medical centres or pay for a personal consultation. Tenenbaum sees buried treasure in the scientific discussions that take place behind closed doors on tumour boards — the groups of doctors, geneticists and researchers who discuss individual cases and decide on the best course of therapy. There are millions of possible combinations of drugs, many more than could ever be tested in clinical trials. Instead, the best oncologists and tumour boards are in effect experimenting on their patients, says Tenenbaum, trying new drug cocktails and seeing what happens. Yet little is learned: the deliberations and failed hypotheses of the tumour boards are not included in individual patients' records, and none of the data are shared outside the hospital. “There's all this experimentation and no learning,” he says. “Every patient presents a vastly complicated data set that we're barely able to interpret,” says C. Anthony Blau, an oncologist at the University of Washington in Seattle who specializes in finding therapies for people with difficult-to-treat breast cancer. The ability to search a large pool of data on what has been tried with others would help oncologists to find the right treatment faster. Tenenbaum is promoting this data-sharing vision through an online portal called Ask Cancer Commons. Patients or their care-givers can upload whatever medical records or genetic tests they have and give a description of their case. A group drawn from more than 100 volunteer oncologists and geneticists, including Blau, then reviews the case and gives feedback, serving as a virtual tumour board. In the short term, Tenenbaum hopes that this will provide a lifeline for people who cannot access top-quality cancer care locally. But as more people take part, the database will grow. Patient data and the reports of the virtual tumour board are fed into a database that doctors can use to help future patients. Cancer Commons follows up to find out what the doctors did with their feedback, and how well it worked. Hospitals are also contributing to the growth of the database. In a pilot test in 2015, 50 cases from three tumour boards were summarized by volunteers and verified by doctors. Eventually, Cancer Commons will have enough of these hand-annotated data to construct algorithms that are capable of picking out important information from complex patient records and tumour-board deliberations without the need for volunteers at all. The project, known as the Insight Network, is currently fundraising and is expected to shift into full gear in the next few years. As such projects grow, the need for people to take charge of their own care will diminish. “Avid patients will lead the way,” says Blau. “The knowledge gained through them will be applicable to the population as a whole.” One of the largest online data-sharing health projects, PatientsLikeMe, began in 2004 with a focus on neurological disorders. Since then, it has expanded to include 2,500 diseases. PatientsLikeMe now has about 500,000 users, most of them seriously ill. Through the website, these people can track their symptoms, join discussions and complete research surveys. Jamie Heywood, a mechanical engineer and co-founder of the site PatientsLikeMe, calls it “a prospective epidemiology platform”. So far, PatientsLikeMe has published more than 75 studies, mostly in collaboration with academic or corporate researchers. It has partnerships with the US Food and Drug Administration and drug company AstraZeneca among others, and it is financed by sharing patients' data with drug companies and researchers. Heywood's younger brother, Stephen, was diagnosed with amyotrophic lateral sclerosis (ALS) in 1998 at the age of 29, spurring Jamie to start the ALS Therapy Development Institute. It took the unusual approach of publishing results in real time as it screened drugs in mice and conducted a stem-cell trial with three participants, including Stephen. People with a serious disease can feel very alone, says Heywood. They want to be treated like partners, not subjects, and this is what PatientsLikeMe tries to do. Sharing data and experiences that may help others, and knowing that they are going to help researchers and drug companies, can make people feel heard and empowered ( et al. Patient http://doi.org/bpqw; 2016). “My brother died eight years ago and he's still helping people,” says Heywood. To build trust and encourage people to share data, the site is designed to be as accessible as possible. Instead of medical terms, patients use phrases such as 'brain freeze' to describe how they feel; the vernacular is then automatically matched with the standard medical code. The company also gets to know its users and adapts how it interacts with them accordingly. Some need to make a decision quickly after a diagnosis, for instance, whereas others with degenerative diseases have more time. Unlike conventional top-down studies, in which data are collected on rigid timetables, PatientsLikeMe offers its users the flexibility to add data whenever they want, but this makes it less statistically rigorous than traditional research. “Real-world observational studies will never be able to match double-blind prospective studies in their ability to examine causality,” says Heywood, and understanding biases in data contributed by users is a big challenge for epidemiologists and others at the company. But when patients are in charge, he says, they supply data that researchers do not normally have access to. As an example of how patient-centred research can yield insights that benefit both patients and drug companies, Heywood points to a collaboration on insomnia between PatientsLikeMe, Northwestern University in Evanston, Illinois, and US drug company Merck & Co. After developing a new sleep drug, surovexant, Merck approached PatientsLikeMe and asked it to look at the sleep patterns of members. Based on an initial survey of 75,000 users, Heywood says that his organization came up with about 50 hypotheses. The team then narrowed both the set of questions and the study group. The resulting survey of just over 5,000 users in 2013 showed that only 13% had been diagnosed with insomnia, but that 73% of those who were undiagnosed also reported symptoms ( et al. Sleep Med. 16, 1332–1341; 2015). The data suggest that many people with serious illnesses have trouble sleeping — something that can exacerbate their condition, and doctors should be aware of the need to manage it. As the five-year study continues, participants will receive information about their individual sleep patterns. Another of the site's self-tracking tools has been particularly useful for Allison Silensky, who has been using PatientsLikeMe since 2008. Silensky, who has a form of bipolar disorder, is a member of the company's user advisory board. The site's mood tracker has helped Silensky to notice and remember trends in her mood that she might otherwise have neglected to mention to her doctor. If she feels great at the doctor's office, she says, “I don't realize that the three weeks prior were horrible because I'm living in the moment.” At first her doctors warned her against getting involved with something on the Internet, she says, but they soon came to see the benefit. After a few years, Silensky saw a trend that she had not noticed before: all her hospitalizations were in spring. Now her doctor adjusts her medication in January, and her therapist checks on her more frequently in spring. She has not been hospitalized since. People with serious and rare diseases, and their families, may be highly motivated to participate in data-sharing projects. But personalized medicine also needs healthy volunteers if researchers are to understand how diseases emerge. “This is a national movement, and we need everyone to participate,” says Bray Patrick-Lake, director of patient engagement at the Duke Translational Medicine Institute in Durham, North Carolina. Research and anecdote alike suggest that the possibility of helping others motivates people to share their data. Unpublished findings from a survey funded by the US National Institutes of Health suggest that proponents of precision medicine will have to convince people that they are contributing to the public good by sharing their data. Sandra Soo-Jin Lee, a biomedical ethicist, is looking at how diverse communities feel about projects that link electronic health records with biobanks for research. Her group at the Stanford Center for Biomedical Ethics in California is still analysing the results, which are based on surveys of 20 focus groups, including Hispanic, Asian and African American people, but already she has found “a tension” in people's attitudes. There is excitement that the data might lead to fresh targeted therapies or discoveries that are possible only with large pools of data. But some worry that the information will be used by the government for non-medical purposes, and others, says Lee, simply feel “a loss of control”. And many are nervous about who will profit. “There's concern about who's actually going to use the data,” she says — particularly that a third party will use the information to develop an expensive therapy. Donating data and tissue for the public good is one thing, but often the benefits are not distributed equally. The HeLa line of immortal cancer cells, for instance, derived without consent from the ovarian tumour of African American woman Henrietta Lacks, has long been a workhorse for cancer researchers. But the benefits of this research have not been distributed equally: cancer mortality rates for African Americans are still higher than those of any other ethnic group in the United States. “In a fundamentally unequal health system, it's harder to argue that everyone should share,” says Barbara Koenig, a medical anthropologist at the University of California, San Francisco. She studies the limits of informed consent in large public data-sharing projects. Without automatic enrolment for enterprises that serve the public good, most people will be motivated to opt into data sharing only when tragedy strikes in the form of a diagnosis for themselves or a loved one, says Koenig. “If people know they will benefit, they will share.” Heywood thinks that the people behind large government projects are misguided if they believe that “because they're trying to do the world good, the world will follow them”. Building trust with people takes time, he says. Continuing to carry out “onerous, top-down recruitment for clinical studies” is not working, says Sharon Terry, chief executive of the Genetic Alliance, a non-profit health advocacy organization. One of its projects, PEER, is an online resource that not only allows patients to make their information available to researchers, but also gives them control over how much of their health information is shared, and with whom, on a case-by-case basis. “Our experiment is to use the tools of social media to engage people,” says Terry. She thinks that the health-care industry does not do outreach as well as community organizations. So the Genetic Alliance is trying to learn from people in education and social services. Today, precision-medicine portals, whether patient-driven or not, are fragmented, and that can make it hard to reach people, admits Giusti. But once people believe they are “on the path to a cure”, they want to participate, she says. The progress made by the Multiple Myeloma Research Foundation towards treating that particular cancer is due in part to the patients who willingly donated their tissue to a biobank in the hope of accelerating research. That project, called CoMMpass, was launched in 2011, and since then has validated several drug targets and treatment strategies. It has shown, for instance, that people treated with a combination of three drugs live longer without the disease progressing than those who are given only two. But these projects are expensive: CoMMpass cost more than $40 million. “We struggle to see how this can be sustained,” says Terry. Large national, and ideally international, projects are the only way to make precision medicine work, says Kathryn North, leader of the Australian Genomics Health Alliance — and most people in the field accept that, she adds. Projects such as the US Precision Medicine Initiative are a great start, but they are only a start. There are economic, political and bureaucratic barriers to overcome, and probably only patients can make it happen. “The biggest advocates for this are the patient groups, because they can see how it transforms health care,” says North. The question facing patient advocates who want to see personalized medicine, says Terry, is this: “Can we impact the culture of large academic institutions, behemoth drug companies, and staid federal agencies?” Even if they want to change, there must be incentives driving them to do so. “I keep banking on public pressure, interest and rallying,” she says. If precision medicine one day comes to benefit broad swathes of the population, it may well be thanks to a few patients who took it on themselves to push for that kind of future.
News Article | December 8, 2016
DUBLIN--(BUSINESS WIRE)--A decade after their work sparked a revolution in patient empowerment and patient-centered medicine, PatientsLikeMe co-founders Jamie and Ben Heywood were awarded the 2016 Humanitarian Award by the International Alliance of ALS/MND Associations. Inaugurated in 2000, the Humanitarian Award recognizes and encourages contributions to the fight against Amyotrophic Lateral Sclerosis/Motor Neurone Disease (ALS/MND) and is awarded to those whose work is of international significance for people affected by ALS/MND. In presenting the award, the Alliance’s citation acknowledged the founding of both the patient network PatientsLikeMe and the ALS Therapy Development Institute (ALS TDI), the world’s first non-profit biotechnology company. “When their brother was diagnosed with ALS at the age of 29, James Allen Heywood and Benjamin Heywood were devastated at his prognosis and at the lack of effective treatments for the disease. They saw firsthand how isolating ALS/MND can be. They took up these challenges as a family and, with family and friends, founded two organizations: ALS TDI, tasked with finding effective treatments for the condition, and PatientsLikeMe, to tackle social isolation and to collect data on what other drugs, interventions or supplements might make a difference to those with ALS/MND.” Jamie Heywood thanked the association on behalf of his family and PatientsLikeMe members and staff and said the company is ready to lead the next decade of advancements in research and medicine, with and for patients. “We changed the rules by helping patients digitize and share their experience so they could make more informed decisions about how to live with and treat their condition. Now we’re embarking on the next stage of the journey by piloting biomarker discovery in ALS and other conditions. We hope many more patients will join us as we work together to find new answers.” More information about how to be part of PatientsLikeMe's upcoming research in ALS/MND is available at www.patientslikeme.com/advanceals. About PatientsLikeMe PatientsLikeMe is a patient network that improves lives and a real-time research platform that advances medicine. Through the network, patients connect with others who have the same disease or condition and track and share their own experiences. In the process, they generate data about the real-world nature of disease that help researchers, pharmaceutical companies, regulators, providers, and nonprofits develop more effective products, services, and care. With more than 400,000 members, PatientsLikeMe is a trusted source for real-world disease information and a clinically robust resource that has published more than 85 research studies. Visit us at www.patientslikeme.com or follow us via our blog, Twitter or Facebook.
News Article | February 15, 2017
DALLAS, Feb. 15, 2017 (GLOBE NEWSWIRE) -- ClubCorp – The World Leader in Private Clubs® (NYSE:MYCC) – today announced that through its Charity Classic events the company raised $3,053,312 in 2016, breaking its previous all-time fundraising record set in 2015. The Charity Classic, ClubCorp’s major philanthropic effort benefiting over 100 national and local charitable organizations, Augie’s Quest/ALS Therapy Development Institute and ClubCorp’s E.P.C.F., has now raised more than $20.3 million since its inception in 2007. A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/0f032b6e-a58d-4706-8b69-606e4b37114a Across the U.S. throughout much of 2016, nearly 15,000 people participated in more than 160 ClubCorp clubs open-to-the-public Charity Classic events. The events, consisting of golf and tennis tournaments, concerts, galas, auctions, 5K runs and unique dining experiences, all benefited the following deserving non-profits: “The Charity Classic has reached this $20 million milestone because of the hard work and dedication of our clubs, their members and employee partners and those in their communities who come together each year to support these very important causes,” said Eric Affeldt, ClubCorp CEO. “I am so proud of what the Charity Classic has become and would like to thank every participant for their support.” Augie Nieto, founder of Augie’s Quest and person with ALS says, “The partnership between Augie’s Quest and ClubCorp continues to exceed expectations. Each club’s team works tirelessly on the events and we are so grateful for the continued support.” The official date for the upcoming 11th annual ClubCorp Charity Classic event is Sept. 29, 2017, with events throughout the country to be held from February through November. For more information on the ClubCorp Charity Classic, visit www.clubcorpcharityclassic.com. About ClubCorp (NYSE:MYCC) Since its founding in 1957, Dallas-based ClubCorp has operated with the central purpose of Building Relationships and Enriching Lives®. ClubCorp is a leading owner-operator of private golf and country clubs and private business clubs in North America. ClubCorp owns or operates a portfolio of over 200 golf and country clubs, business clubs, sports clubs, and alumni clubs in 26 states, the District of Columbia and two foreign countries that serve over 430,000 members, with approximately 20,000 peak-season employees. ClubCorp Holdings, Inc. is a publicly traded company on the New York Stock Exchange (NYSE:MYCC). ClubCorp properties include: Firestone Country Club (Akron, Ohio); Mission Hills Country Club (Rancho Mirage, California); The Woodlands Country Club (The Woodlands, Texas); Capital Club Beijing; and Metropolitan Club Chicago. You can find ClubCorp on Facebook at facebook.com/clubcorp and on Twitter at @ClubCorp.
News Article | February 22, 2017
Orangetheory® Fitness, with 21 locations in the Tampa Bay area, announced it has partnered with Augie’s Quest, a foundation dedicated to finding a cure for amyotrophic lateral sclerosis (ALS) disease, with the goal of raising $1 million in two weeks. The company’s first national fundraiser, named the #IBurnForALS campaign, will take place from Feb. 20 to March 5. During the two-week period, more than 570 Orangetheory Fitness studios around the country will encourage members to donate money to support Orangetheory’s quest to reach $1 million. All money raised will be donated to Augie’s Quest in support of ALS research. The #IBurnForALS fundraising campaign will consist of Orangetheory Fitness coaches challenging participants in each class during the two week period to donate at least $1 per splat point achieved. Splat points are attained for every minute a participant spends in the ‚orange zone,’ which is their target-training zone of 84 percent to 91 percent of their heart rate. The orange zone stimulates metabolism and increases energy. In addition, on Saturday, February 25, Orangetheory will host Augie-thon, a specialty donation session at every studio. Augie-thon is a unique 90-minute Orangetheory class that members and non-members can attend for a donation of $20. The first 45 participants at each studio will receive a special black or orange sweatband. Tampa Bay however has added to this special initiative. Coaches will do workouts, rowing and burpees corresponding to dollars donated, and members can create their own class playlist with a $500 donation, or host their own VIP class with a $1000 donation. “ALS is a disease that with the proper research and funding, we can prevent. The Tampa Bay stores have employees and members that have been affected and we are committed to this National Partnership, as we want to exceed fundraising goals, to help Burn for ALS.” Says Don Allen, CEO of Tampa Fitness Partners. Augie’s Quest was co-founded by Augie Nieto and his wife, Lynne. Nieto is known for his role in shaping today’s fitness world as the co-founder and CEO of Life Fitness, Lifecycle and Octane Fitness. He was diagnosed with ALS in 2005 and has been dedicated to finding treatments and cures for the disease ever since through events, partnerships and fundraising activities around the globe. Augie’s Quest directly funds the ALS Therapy Development Institute (ALS TDI), the world’s foremost drug discovery center focused solely on finding a cure for ALS. The Institute’s innovative science and cutting edge approach has resulted in the identification of AT-1501, a promising treatment for ALS. ALS TDI also pioneered the ALS Precision Medicine Program, the world’s premier program and partnership with ALS patients to discover additional potential treatments. ALS, also known as Lou Gehrig’s disease, is a disorder that affects the function of nerves and muscles. More than 6,000 people in the U.S. are diagnosed with ALS each year. The life expectancy of a person with ALS averages two to five years from the time of diagnosis, however there is evidence that people with ALS are living longer, at least partially due to clinical management interventions, riluzole and other compounds and drugs under investigation. For more information about the #IBurnForALS campaign, please visit your nearest Tampa Bay Orangetheory Fitness studio. To learn more about Augie’s Quest, please visit AugiesQuest.org. Members and non-members alike can make donations at AugiesQuest.ALS.net/OTF. About Orangetheory Fitness: Orangetheory® Fitness (http://www.orangetheoryfitness.com) is a scientifically designed, one-of-a-kind, group personal training workout broken into intervals of cardiovascular and strength training. Backed by the science of excess post-exercise oxygen consumption (EPOC), Orangetheory’s heart-rate-monitored workouts are designed to get participants within the target-training zone of 84 percent to 91 percent of their heart rate, which stimulates metabolism and increases energy. Led by highly skilled coaches, each Orangetheory Fitness workout incorporates endurance, strength and power elements through a variety of equipment including treadmills, rowing machines, TRX® suspension training and free weights. The end result is more energy, visible toning and the ‚Orange Effect’ – where participants keep burning calories for up to 36 hours post-workout (the Orangetheory Fitness ‚afterburn’) for an average of 500+ total calories burned per every 60-minute workout. The company was ranked #60 in Inc. magazine’s Fastest Growing Private Companies List and #225 in Entrepreneur’s 2016 Franchise 500® list of the top franchises in the world.
Hatzipetros T.,ALS Therapy Development Institute |
Bogdanik L.P.,The Jackson Laboratory |
Tassinari V.R.,ALS Therapy Development Institute |
Kidd J.D.,ALS Therapy Development Institute |
And 7 more authors.
Brain Research | Year: 2014
ALS therapy development has been hindered by the lack of rodent animal models. The discovery of TDP-43, a transcription factor that accumulates in the cytoplasm of motor neurons (MNs) in most cases of ALS, prompted attempts to develop TDP-43-based models of the disease. The current study sought to examine, in extensive detail, the emerging disease phenotype of a transgenic mouse model that overexpresses a mutant human TDP-43 (hTDP-43) gene under mouse prion promoter control. Careful attention was given to ALS-like characteristics to determine the appropriateness of this model for testing therapies for ALS. In light of previous reports that gastrointestinal (GI) dysfunction is responsible for early death in these mice, gut immunohistochemistry (IHC) and longitudinal gut motility assays were used to identify the onset and the progression of these defects. IHC studies revealed that site-specific overexpression of the hTDP-43 transgene in colonic myenteric plexes resulted in progressive neurodegeneration in this region. This change was associated with progressively reduced GI motility, culminating in frank stasis that was primarily responsible for decreasing longevity in these mice. The disease phenotype was gender- and genetic background-dependent, with congenic C57BL/6J male mice exhibiting the most aggressive form of the disease. Spinal cord IHC revealed ubiquitin-positive inclusions, but not TDP-43 aggregates, in the cytoplasm of MNs. Neither gender exhibited compelling ALS-like neuromuscular deficits, irrespective of age. While this model may be useful for studying GI tract neurodegeneration, in its present state it does not display a phenotype suitable for testing ALS therapeutics. This article is part of a Special Issue entitled RNA Metabolism 2013. © 2013 Elsevier B.V.
Lincecum J.M.,ALS Therapy Development Institute |
Vieira F.G.,ALS Therapy Development Institute |
Wang M.Z.,ALS Therapy Development Institute |
Thompson K.,ALS Therapy Development Institute |
And 10 more authors.
Nature Genetics | Year: 2010
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Using unbiased transcript profiling in an ALS mouse model, we identified a role for the co-stimulatory pathway, a key regulator of immune responses. Furthermore, we observed that this pathway is upregulated in the blood of 56% of human patients with ALS. A therapy using a monoclonal antibody to CD40L was developed that slows weight loss, delays paralysis and extends survival in an ALS mouse model. This work demonstrates that unbiased transcript profiling can identify cellular pathways responsive to therapeutic intervention in a preclinical model of human disease. © 2010 Nature America, Inc. All rights reserved.
Als Therapy Development Institute | Date: 2012-11-29
Methods and therapeutic compositions are disclosed for treating neurodegenerative disorders and, in particular Amyotrophic Lateral Sclerosis, using sphingosine1-phosphate receptor modulators, such as fingolimod or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
Als Therapy Development Institute | Date: 2012-02-23
Methods and therapeutic agents are disclosed for treating neurodegenerative disorders by depletion of CD8 positive T cells by using antibodies, FAb fragments of antibodies or similar agents that sequester, neutralize or deplete the CD8+ cytotoxic T cells.
PubMed | ALS Therapy Development Institute
Type: Journal Article | Journal: PloS one | Year: 2015
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. The mechanisms leading to motor neuron degeneration in ALS are unclear. However, there is evidence for involvement of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in ALS, notably in mutant SOD1 mediated models of ALS. Stress induced phosphorylation of the eIF2 alpha subunit by eukaryotic translation initiation factor 2-alpha kinase 3 Perk activates the UPR. Guanabenz is a centrally acting alpha2 adrenergic receptor agonist shown to interact with a regulatory subunit of the protein phosphatase, Pp1/Gadd34, and selectively disrupt the dephosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eif2alpha). Here we demonstrate that guanabenz is protective in fibroblasts expressing G93A mutant SOD1 when they are exposed to tunicamycin mediated ER stress. However, in contrast to other reports, guanabenz treatment accelerated ALS-like disease progression in a strain of mutant SOD1 transgenic ALS mice. This study highlights challenges of pharmacological interventions of cellular stress responses in whole animal models of ALS.
PubMed | ALS Therapy Development Institute
Type: | Journal: Journal of visualized experiments : JoVE | Year: 2015
The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.