ALS

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Given the expansion of indications for genetic testing and our understanding of conditions for which the results change medical management, it is imperative to consider novel ways to deliver care beyond the traditional genetic counseling visit, which are both amenable to large-scale implementation and sustainable. The investigators propose an entirely new approach for the implementation of genomic medicine, supported by the leadership of Penn Medicine, investigating the use of non-geneticist clinician and patient nudges in the delivery of genomic medicine through a pragmatic randomized clinical trial, addressing NHGRI priorities. Our application is highly conceptually and technically innovative, building upon expertise and infrastructure already in place. Innovative qualities of our proposal include: 1) Cutting edge EHR infrastructure already built to support genomic medicine (e.g., partnering with multiple commercial genetic testing laboratories for direct test ordering and results reporting in the EHR); 2) Automated EHR-based direct ordering or referring by specialist clinicians (i.e., use of replicable modules that enable specialist clinicians to order genetic testing through Epic Smartsets, including all needed components, such as populated gene lists, smartphrases, genetic testing, informational websites and acknowledgement e-forms for patient signature); 3) EHR algorithms for accurate patient identification (i.e., electronic phenotype algorithms to identify eligible patients, none of which currently have phenotype algorithms present in PheKB; 4) Behavioral economics-informed implementation science methods: This trial will be the first to evaluate implementation strategies informed by behavioral economics, directed at clinicians and/or patients, for increasing the use of genetic testing; further it will be the first study in this area to test two forms of defaults as a potential local adaptation to facilitate implementation (ordering vs. referring); and 5) Dissemination: In addition to standard dissemination modalities,PheKB95, GitHub and Epic Community Library, the investigators propose to disseminate via AnVIL (NHGRI's Genomic Data Science Analysis, Visualization, and Informatics Lab-Space). Our results will represent an entirely new paradigm for the provision of genomic medicine for patients in whom the results of genetic testing change medical management.

The goal of this observational study is to learn how speech and breathing change over time in Spanish-speaking individuals with amyotrophic lateral sclerosis (ALS) compared to age- and gender-matched individuals without ALS. The main questions it aims to answer are: Can speech and breathing measures collected through a smartphone application serve as reliable digital biomarkers to track bulbar disease decline in Spanish-speaking people with ALS? How do these measures differ between individuals with ALS and those without ALS? Researchers will compare Spanish-speaking participants with ALS to age- and gender-matched healthy controls to see if specific speech and breathing features can identify or predict bulbar decline. Participants will: Use a Spanish-language smartphone application to record speech and breathing tasks over time. Complete assessments of speech, breathing, and functional abilities (e.g., ALS Functional Rating Scale). Provide data that will be compared to caregiver reports and clinical outcomes to validate new digital biomarkers.

This is a multi-site study of ALS participants and healthy controls who will undergo brain and cervical spine MRIs and NfL blood testing at up-to 4 time points over the course of a year. The primary goal is to identify objective biomarkers of disease progression that are biologically relevant, linearly progressive, and sensitive to change.

The goal of the Healey ALS MyMatch Common Screening Protocol (MCSP), an observational study, is to identify individuals with ALS who may be eligible to be matched to a currently enrolling ALS MyMatch trial. Participants will complete a MCSP Screening Visit and undergo clinical assessments, laboratory testing, and biomarker analyses to determine preliminary trial eligibility. The study also characterizes clinical, genetic, and biofluid biomarker profiles, assesses the prevalence of ALS-associated gene variants, and banks blood samples for future ALS and biomarker research. MCSP enables simultaneous screening for multiple trial-specific biomarkers and uses a targeted medical history form to optimize matching of participants to appropriate MyMatch trials.

The goal of this clinical trial is to learn whether a nasal spray medicine called foralumab is safe and easy to tolerate in adults with amyotrophic lateral sclerosis (ALS). ALS is a disease that slowly damages the nerve cells that control movement, causing muscles to grow weaker over time. Foralumab is being studied as a possible way to calm the inflammation and immune system activity that are thought to play a role in ALS. The main questions it aims to answer are: 1. Is nasal foralumab safe for people with ALS, and how well do they tolerate it over 12 and 24 weeks of treatment? 2. Does foralumab change certain markers in the blood and spinal fluid, and lower inflammation in the brain, compared with a placebo? Researchers will compare people who take foralumab to people who take a placebo (a matching nasal spray with no medicine in it) to see how the two groups differ in safety and in these markers. About 44 adults aged 18 to 75 with ALS will take part. For the first 12 weeks, participants will be randomly assigned so that about 3 in 4 use foralumab and about 1 in 4 use the placebo. Neither the participants nor the study staff will know who is using which during this time (this is called "double-blind"). After the first 12 weeks, everyone who continues will use foralumab for the next 12 weeks. Participants will: * Spray the study treatment into both nostrils 3 times a week, on alternate days, in cycles of 2 weeks on treatment followed by 1 week off * Learn to use the nasal spray device so they or a caregiver can give most doses at home * Take part for about 8.5 months in total, which includes screening, 24 weeks of treatment, and a safety check-in about 4 weeks after the last dose * Attend some visits at the study clinic and complete others remotely by phone or video * Have study tests that may include blood samples, breathing and muscle-strength checks, and - for those who agree and at certain study centers - spinal fluid samples and brain scans to measure inflammation

This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

People with brainstem stroke, advanced amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), or other disorders can become unable to move or speak despite being awake and alert. In this project, the investigators seek to further translate knowledge about interpreting brain signals related to movement, and to further develop an intracortical brain-computer interface (iBCI) that could restore rapid and intuitive use of communication apps on tablet computers by people with paralysis.

This is a data repository for multi-site multi-protocol clinic-based Natural History Study of ALS and Other Motor Neuron Disorders (MND). All people living with ALS or other MNDs who attend clinics at the Study hospitals (sites) are offered to participate in the Study. The Sites collect so-called Baseline information including demographics, disease history and diagnosis, family history, etc. At each visit, the Sites also collect multiple disease-specific outcome measures and events. The information is captured in NeuroBANK, a patient-centric clinical research platform. The Sites have an option to choose to collect data into 20+ additional forms capturing biomarkers and outcome measures. Captured data after its curation are anonymized (all personal identifiers and dates are being removed), and the anonymized dataset is shared with medical researchers via a non-exclusive revocable license. Funding Source - Biogen, Inc.; Mitsubishi Tanabe Pharma America; FDA OOPD.

INdependence Through Endovascular Neuroprosthetic Technology (INTENT): an Early Feasibility Study

Test the feasibility of using electrocorticography (ECoG) signals to control complex devices for motor and speech control in adults severely affected by neurological disorders.

Functional Outcomes and Control Using Synchron BCI - Canada (FOCUS-CAN)

This study is a placebo-controlled Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide (ASO) AMX0114 in adult participants with amyotrophic lateral sclerosis (ALS).

1. Establish the safety and tolerability of the 5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide (\[11C\]CPPC) PET radioligand in ALS patients and controls 2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype. 3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers 4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.

FIH, Phase 1/2, multi-centre, randomised, double-blind, placebo controlled study with an optional open-label dosing extension to assess the safety, tolerability, efficacy, and Pharmacodynamics (PD) of single or multiple (up to 48 weeks QD) subcutaneous (SC) doses of PLL001 compared to placebo in subjects diagnosed with ALS.

The goal of this study is to investigate whether high-density electrocorticography (ECoG) signals recorded from the surface of the brain can be used to decode neural representations of Mandarin Chinese speech features, including lexical tone, without requiring overt speech movements. The study focuses on the development and evaluation of decoding algorithms based on neural activity recorded during clinically indicated neurosurgical procedures. The main questions it aims to answer are: Can high-density ECoG signals be decoded to reconstruct neural representations of Mandarin Chinese speech features, particularly lexical tone? Can neural activity recorded during silent auditory speech imagery be decoded to reconstruct tone-specific speech representations without actual articulation? The study includes two groups of adult patients with neurological conditions who require cortical electrode placement as part of clinically indicated care: A intraoperative high-density ECoG temporary coverage group, enrolling approximately 50 patients with functional-area glioma or drug-resistant epilepsy who undergo awake neurosurgery with temporary high-density ECoG coverage for clinical functional mapping. A permanent high-density ECoG implantation group, enrolling approximately 10 patients with severe speech or language impairment caused by neurological conditions such as stroke, brain tumors, amyotrophic lateral sclerosis (ALS), or locked-in syndrome, who receive permanent high-density cortical electrode implantation for long-term monitoring. Participants will: Complete preoperative clinical assessments as part of standard medical care, including brain imaging, language function evaluation, and routine neurological assessments Undergo clinically indicated awake neurosurgical procedures during which high-density ECoG electrodes are placed on the cortical surface for clinical functional localization Perform language-related tasks, such as listening to speech, imagining speech, and limited spoken responses, while brain electrical activity is recorded for approximately 20-30 minutes during surgery, without altering standard surgical procedures For participants in the permanent implantation group, participate in long-term follow-up visits approximately every 2 weeks or monthly for up to 12 months after surgery, including evaluation of signal quality and research-related analysis and optimization of decoding algorithms All surgical procedures involving temporary or permanent electrode placement are performed for clinical indications and have been approved through institutional ethical and scientific review. Participation in this study does not alter standard clinical care for the temporary recording group and does not require additional clinical procedures beyond routine treatment. This research aims to support the long-term development of silent brain-to-speech communication technologies for individuals with severe speech or motor impairments and to improve understanding of how frontal, parietal, and temporal brain regions represent imagined speech in tonal languages such as Mandarin Chinese.

This is a study of Kamlanoflast in patients with ALS. Kamlanoflast is orally administered over 24 weeks. Its effects on inflammatory and functional parameters will be studied. Information on safety and tolerability will be collected.

This program provides family members of individuals with familial ALS the opportunity to contribute to research focused on learning more about why motor neuron degeneration begins and how or why it progresses. This study provides genetic counseling and testing to help participants understand and manage their risk and determine if they want to learn their genetic status. This study will follow unaffected ALS gene mutation carriers on an annual basis to gather essential information that will ultimately help researchers develop novel therapies for the prevention and treatment of ALS.

The goal of this interventional trial is to learn about lung volume recruitment (LVR) and expiratory muscle strength training (EMST) in a total of up to 39 patients diagnosed with ALS. The following aims will be addressed: 1. Determine the impact of combined LVR and EMST on cough strength and respiratory function in individuals with ALS. 2. Determine the impact of combined LVR and EMST on patient-reported dyspnea and bulbar impairment. 3. Describe the effect of combined LVR and EMST on patient- and caregiver reported burden and quality of life.

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that causes gradual muscle weakness and loss of muscle mass. It affects all muscles that control movement, speech, swallowing, and breathing. Unfortunately, ALS is currently incurable, and treatments are limited. Only two medications, riluzole and edaravone, have been approved and can slightly extend survival, typically between 20 and 48 months from diagnosis. Recent research has identified a useful biomarker known as neurofilament light chain (NfL), which increases in the blood as nerve cells become damaged. Measuring NfL levels can help track the progression of ALS. A promising non-invasive treatment called transcranial direct current stimulation (tDCS) has shown potential benefits for patients with ALS. tDCS involves safely applying mild electrical currents to specific areas of the brain and spinal cord. This approach aims to stimulate nerve cells, potentially improving their function and slowing disease progression. Initial studies have reported temporary improvements in muscle strength and survival when tDCS was used over a short period. Based on these encouraging results, our study proposes a new home-based tDCS treatment program specifically designed for ALS patients. Participants will use an easy-to-operate, safe, and portable device at home. The treatment involves placing electrodes on the scalp and the neck area to stimulate both the motor areas of the brain and the spinal cord. Therapy sessions will occur five days per week over 16 weeks. This home-based approach allows patients to comfortably receive therapy without daily trips to the hospital, making treatment more accessible and convenient. By providing this therapy at home, the investigators aim to improve the quality of life for ALS patients and explore new possibilities in treating and managing ALS and other neurodegenerative diseases.

The goal of this observational study is to identify molecular features in multiple clinical samples and/or the patient environment that are associated with ALS. Participants will collect biological samples and answer questionnaires regarding their health at each appointment with their ALS practitioner.

The New York Stem Cell Foundation (NYSCF) Research Institute is performing this research to accelerate diverse disease research using cells from the body (such as skin or blood cells) to make stem cells and other types of cells, conduct research on the samples, perform genetic testing, and store the samples for future use. Through this research, researchers hope to identify future treatments or even cures for the major diseases of our time.

The goal of this study is to learn from discordant twins affected by Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia the contribution of genetic background versus environmental exposure. The main questions it aims to answer is: * How far does the genetic background explain the onset of ALS/FTD in discordant twins? * Which environmental factors and events occurring in post-fetal life influence the onset or progression of this neurodegenerative condition? Participants with ALS and/or FTD with a monozygotic or dizygotic twin willing to contribute to this research will be followed up for two years by specialized Motor Neuron Disorders centers in Italy, donating biological specimen for -omic sciences analysis, and checking out if prodromal signs/symptoms of these two conditions will develop during time.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease in the human motor system characterized by the selective involvement of spinal cord anterior horn cells, brainstem motor nuclei, and the corticospinal tract. It predominantly presents as concurrent damage to upper and lower motor neurons. Induced pluripotent stem cells (iPSCs) are a type of induced pluripotent stem cell derived from autologous or allogeneic cell sources. They can differentiate into various functional cell types, including specific motor neuron cells. iPSCs are used for stem cell replacement therapy. iPSCs hold significant clinical potential for ALS treatment. The iPSC database with human leukocyte antigen characteristics may represent a promising technology. This technology has the potential to obtain high-quality cell products and reduce the risk of graft rejection. Moreover, human iPSCs have demonstrated a certain degree of efficacy in the transplantation of neural stem/progenitor cells derived from ALS rodent models. The potential mechanisms of iPSC therapy for ALS include: the differentiated motor neuron precursor cells can replace damaged motor neurons, and restore motor conduction function; by secreting neurotrophic factors, they protect neurons; through immune regulation, they inhibit inflammatory reactions, and slow the progression of ALS. Xellsmart Biomedical (Suzhou) Co., Ltd. is developing an injectable solution for ALS treatment using human iPSC-derived motor neuron precursor cells to address the pressing need for ALS therapy.

The goal of this observational study is to learn about the emotional perception in people with ALS disease compared to people with other neuromuscular disease and healthy controls. The main questions it aims to answer are: * How people with ALS judge happy and angry faces and what their "insight" into these judgements are like * How their autonomic responses differ from the other two test group Participants will asked to judge if a face presents a happy emotion or angry emotion. Researchers will compare the ALS group responses with neuromuscular diseases group and healthy control group responses to see if the ALS group judge more happy faces than angry.