amyotrophic lateral sclerosis

Original title: “Amyotrophic Lateral Sclerosis.”

insertion or deletion variants in taf15 exon 15 are genetic factors impacting the prognosis of amyotrophic lateral sclerosis in a japanese cohort

Original title: “Insertion or deletion variants in TAF15 exon 15 are genetic factors impacting the prognosis of amyotrophic lateral sclerosis in a Japanese cohort.”

The key issues for industry and FDA as the Orphan Drug Act hits its 40th anniversary. The key issues for industry and FDA as the Orphan Drug Act hits its 40th anniversary. ... As patients and the public health community mark the 40th anniversary of the Orphan Drug Act of 1983, biopharma companies and FDA officials are acknowledging continued challenges in testing, approving, and producing new treatments for critical conditions affecting small patient populations. And recent legislation has established an initiative to accelerate the development of more effective treatments for amyotrophic lateral sclerosis (ALS) through an FDA Rare Neurodegenerative Disease grants program].5 The awards aim to cover R&D costs of new therapies for ALS and a range of rare neurogenerative diseases in adults and children, as spelled out in an FDA action plan issued in June 2022. Efforts to advance rare disease treatments, however, may be stymied by the ongoing legal battle that has raised challenges to FDA policies governing the scope of orphan drug exclusivity policy. Despite that court ruling, FDA has insisted that it will continue to tie orphan drug exclusivity only to approved uses or indications.6 The agency has pressed Congress to enact legislation to clarify this stance, but so far has failed to gain action on Capitol Hill. The program has led to market approval of more than 600 therapies to treat serious diseases affecting less than 200,000 patients in the US, investment spurred by grants and tax credits to help fund very small clinical trials, exemptions from hefty user fees, plus seven years added of marketing exclusivity for approved orphans and more incentives for developing rare disease treatments for children.1 · FDA notes that orphan therapies accounted for more than half of novel new drugs approved in 2022, and that the agency already has approved two notable rare disease treatments this year.

Original title: “Kudos and Hurdles in Tackling Rare Diseases | Applied Clinical Trials Online”

recognition and treatment of concurrent amyotrophic lateral sclerosis and multiple sclerosis

Original title: “Recognition and Treatment of Concurrent Amyotrophic Lateral Sclerosis and Multiple Sclerosis.”

insights into x linked dystonia parkinsonism and spinocerebellar ataxia type 36 through the lens of amyotrophic lateral sclerosis frontotemporal dementia

Original title: “Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.”

Ulefnersen, an RNA-targeted therapy being developed by Ionis Pharmaceuticals and Otsuka Pharmaceutical, improved measurements of functional impairment and survival in patients with a rare, genetic ALS subtype in a Phase 3 trial. The partners plan to approach the FDA with the results to determine potential pathways for approval.

Original title: “Ionis-Otsuka offer 'groundbreaking' improvement in function and survival for genetic type of ALS”

Ulefnersen met its primary end point in the phase 3 FUSION trial, providing the first placebo-controlled evidence for a genetically targeted therapy in FUS-ALS. “We are profoundly grateful to the patients, carers, families, investigators and study teams whose commitment made this study possible,” Kunal Gandhi, MD, MPH, Vice President, Head of Global Clinical Development, at Otsuka, told NeurologyLive®. “These findings represent a major advancement for people living with FUS-ALS, a rare and often rapidly progressive genetic form of ALS. There are currently no approved therapies specifically targeting the underlying genetic cause of FUS-ALS, underscoring the significant unmet need for effective treatment options. As the first FUS-ALS clinical trial to meet its primary endpoint, FUSION provides compelling evidence that a targeted genetic approach may help alter the course of disease.” Otsuka Pharmaceutical and Ionis Pharmaceuticals announced positive topline results from the phase 3 FUSION trial (NCT04768972) evaluating ulefnersen, an investigational antisense oligonucleotide (ASO), in patients with a rare genetic subtype of amyotrophic lateral sclerosis (ALS) driven by mutations in the fused in sarcoma (FUS) gene, known as FUS-ALS.1 · According to the companies, the trial met its primary end point, showing a statistically significant improvement on a composite measure of functional decline and survival, marking the first placebo-controlled clinical evidence for an agent designed to target the underlying genetic cause of the disease. “Today’s Phase 3 FUSION topline results mark a major milestone for people living with FUS-ALS, re-shaping what is possible for a community that has long faced this devastating disease with limited treatment options,” John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka, said in a statement.1 “As the first FUS-ALS clinical trial to meet its primary endpoint, FUSION provides compelling evidence that a targeted genetic approach may help alter the course of disease.” FUS-ALS accounts for an estimated 0.6% of ALS cases overall but a disproportionate share of pediatric and juvenile-onset disease, with FUS variants implicated in an estimated 43% to 52% of cases in that population.2 The disease typically presents with rapid progression, and early-onset cases can progress to respiratory failure and death in 1 to 2 years of symptom onset. No therapy targeting the underlying FUS mutation has previously been approved.

Original title: “Ulefnersen Meets Primary End Point in Phase 3 FUSION Trial for FUS-ALS | NeurologyLive - Clinical Neurology News and Neurology Expert Insights”

Single-patient antisense oligonucleotide for rare CHCHD10 mutation shows functional gains over 12 months Single-patient antisense oligonucleotide for rare CHCHD10 mutation shows functional gains over 12 months ... When a personalized RNA therapy was administered to a patient with amyotrophic lateral sclerosis (ALS) caused by a genetic mutation, the patient’s physical function improved. A joint research team from the Department of Molecular Medicine at Mayo Clinic in Rochester, USA, and the Department of Genetics at Orlando Health, USA, developed and administered an individualized antisense oligonucleotide (ASO) therapy to treat a single clinical trial participant, and reported that the patient showed significant symptom improvement one year later. The results were published on the 14th in the international journal Med. ALS is also known as Lou Gehrig’s disease. The research team stated, “We have shown that it is possible to develop a personalized ASO therapy for CHCHD10-related ALS,” adding that this provides “evidence suggesting the potential for therapeutic benefit in the clinic.” ... Copyright ⓒ DongA Science. All rights reserved. ... An ALS patient, unable to move the muscles required for speech, has successfully translated their thoughts into words on a digital device using a tech · New Treatment Strategy Discovered for Lou Gehrig's Disease, Which Paralyzes Muscles The case suggests personalized RNA therapies may be feasible even for rare hereditary forms of ALS.

Original title: “Mayo Clinic develops personalized RNA therapy that improves ALS motor scores - DongA Science”

weak association of pathogenic erbb4 variants with amyotrophic lateral sclerosis

Original title: “Weak association of pathogenic ERBB4 variants with amyotrophic lateral sclerosis.”

caregivers in amyotrophic lateral sclerosis als preliminary results between paid care and family care

Original title: “Caregivers in amyotrophic lateral sclerosis (ALS): preliminary results between paid care and family care.”

The TREM2 stabilizer failed to show efficacy in a Phase 2 trial of patients with early-stage ALS. This development follows two late-stage trial failures reported by Novartis last week, plus the news that the pharma has paused multiple CAR T cell trials following patient deaths.

Original title: “Novartis halts TREM2 targeting ALS program in 4th trial stumble in a month”

atherosclerotic cardiovascular diseases increase als risk by 82 while optimal cardiovascular health halves it a 0 5 million prospective cohort study

Original title: “Atherosclerotic Cardiovascular Diseases Increase ALS Risk by 82% While Optimal Cardiovascular Health Halves It: A 0.5-Million Prospective Cohort Study.”

living with amyotrophic lateral sclerosis exploring what matters to patients and caregivers through their experiences

Original title: “Living with Amyotrophic Lateral Sclerosis: Exploring what matters to patients and caregivers through their experiences.”

emergencies in amyotrophic lateral sclerosis

Original title: “Emergencies in Amyotrophic Lateral Sclerosis.”

familial neuropathological and cellular analysis identify arpp21 as a major amyotrophic lateral sclerosis associated gene in french cohorts

Original title: “Familial, neuropathological and cellular analysis identify ARPP21 as a major amyotrophic lateral sclerosis associated gene in French cohorts.”

jp1 peptide modulates oxidative stress and autophagy via keap1 nrf2 are in als model mice

Original title: “JP1 peptide modulates oxidative stress and autophagy via Keap1-Nrf2-ARE in ALS model mice.”

bridging the gap neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis

Original title: “Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.”

incidence and clinical characteristics of amyotrophic lateral sclerosis during the post covid 19 period a population based study from isfahan iran

Original title: “Incidence and clinical characteristics of amyotrophic lateral sclerosis during the post-COVID-19 Period: a population-based study from Isfahan, Iran.”

The Biotech Consortium to Accelerate ... therapies for serious neurological and rare diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, Angelman syndrome, and Duchenne muscular dystrophy. BCAI's mission is to keep American clinical trials in the U.S., ... The Biotech Consortium to Accelerate Innovation (BCAI) unites more than a dozen innovative biotechnology companies developing transformative therapies for serious neurological and rare diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, Angelman syndrome, and Duchenne muscular dystrophy. BCAI's mission is to keep American clinical trials in the U.S., so American patients have the earliest possible access to U.S.-developed medical innovation. CAMBRIDGE, Mass.--(BUSINESS WIRE)--A new survey reveals that U.S. biotechnology companies focused on developing treatments for rare and serious diseases overwhelmingly prefer to conduct first-in-human (FIH) clinical trials in the United States. However, historical obstacles posed by the U.S. Through strategic cost-saving initiatives, robust business partnerships, educational and networking opportunities, and proactive advocacy, MassBio empowers its members to launch the next generation of medical advancements to deliver the cures and therapies that enhance patient lives. ... 1U.S. Food and Drug Administration. Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers: Guidance for Industry. Instead, they are asking the FDA to implement the 10x safety margin as outlined in the Agency’s own 2005 guidance, Estimating the Maximum Safe Starting Dose in Initial Clinical Trials1. Restore predictable review timelines that reduce costly holds and rework. Strengthen sponsor-reviewer communication so trial design is driven by science, not procedural ambiguity. Ensure better alignment of review criteria with disease severity and life expectancy.

Original title: “New Survey Finds U.S. Biotechs Advancing Treatments for Rare and Serious Diseases Want to Run Clinical Trials in U.S. but Regulatory Hurdles are Sending Them Abroad”