Qalsody (tofersen)
Research Synopsis
- Qalsody (tofersen) is the first FDA-approved treatment targeting amyotrophic lateral sclerosis (ALS) in patients with specific mutations in the SOD1 gene, demonstrating a significant milestone for gene therapy in ALS.
- The FDA approval was granted on April 25, 2023, emphasizing the drug’s unique mechanism as an antisense oligonucleotide designed to reduce protein levels associated with the genetic mutation.
- A recent multicenter cohort study showed that tofersen significantly reduced neurofilament light chain (NfL) levels, a biomarker of neurodegeneration, while being generally well tolerated in patients with ALS.
- A literature review highlighted that while tofersen has shown promise in some patients, its efficacy is not uniform across all cases, illustrating the complexities of ALS treatment.
- The VALOR study that assessed tofersen didn’t meet its primary endpoint, yet it offered encouraging evidence regarding lowering plasma NfL levels, suggesting potential in early intervention strategies for ALS patients.
- Studies have identified cytokines and immune responses linked to tofersen treatment, indicating potential autoimmune reactions that need further research for comprehensive patient safety understanding.
- Ongoing investigations into the mechanism of action of antisense oligonucleotides, including tofersen, reveal advancements in targeting RNA to hinder the progression of ALS and other progressive neurological disorders.
- Recent findings indicate that while tofersen represents a major advancement in ALS treatment, continued exploration into gene therapies and alternative approaches is necessary for optimal patient outcomes.
- The emerging research landscape suggests that personalized medicine, based on genetic profiles, may lead to future therapies better tailored for patients suffering from ALS.
- Overall, the approval and ongoing research surrounding tofersen signal a hopeful shift in the treatment paradigm for ALS, yet the challenge remains in ensuring effective outcomes for all patients affected by this debilitating condition.
Qalsody (tofersen)
Tofersen: First Approval.
London, UK
2 hours ago
1 Received
- Tofersen (Qalsody) is an antisense oligonucleotide developed by Biogen aimed at treating amyotrophic lateral sclerosis (ALS).
- It received FDA approval on April 25, 2023, specifically for ALS patients with a mutation in the SOD1 gene.
- The article outlines key milestones in the development process that led to this historic approval for ALS treatment.
$100 - $150
Hourly Rate
Tofersen (Qalsody) for ALS.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
From Failure to Meet the Clinical Endpoint to U.S. Food and Drug Administration Approval: 15th Antisense Oligonucleotide Therapy Approved Qalsody (Tofersen) for Treatment of Mutated Amyotrophic Lateral Sclerosis.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
ASO drug Qalsody (tofersen) targets amyotrophic lateral sclerosis.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases.
London, UK
2 hours ago
1 Received
- - 5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are distinct neurological disorders causing lower motor neuron degeneration, with nusinersen and tofersen as their respective treatments.
- - A case series reported cytological findings in cerebrospinal fluid (CSF) of two patients, showing similar macrophage inclusions (referred to as "asophages") after starting ASO treatments.
- - Although both nusinersen and tofersen have been well tolerated, the implications of these macrophage inclusions during long-term ASO therapy remain unclear and deserve further investigation.
$100 - $150
Hourly Rate
2023 FDA TIDES (Peptides and Oligonucleotides) Harvest.
London, UK
2 hours ago
1 Received
- In 2023, the FDA approved nine TIDES, including four oligonucleotides targeting disorders like ALS, geographic atrophy, primary hyperoxaluria type 1, and hereditary transthyretin-mediated amyloidosis, all with enhanced stability and effectiveness.
- The approved peptides exhibit a variety of structures (linear, cyclic, and lipopeptides) and applications, including the first orphan drug designation for a peptide-based chemokine antagonist.
- Notably, a peptide-based treatment was approved for core symptoms of Rett syndrome, with the analysis of TIDES focusing on their chemical structure, medical targets, and potential side effects.
$100 - $150
Hourly Rate
Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis.
London, UK
2 hours ago
1 Received
- Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disease that primarily affects muscle control due to the death of motor neurons, and current treatments mainly offer symptomatic relief.
- Tofersen, recently approved by the FDA as Qalsody, is the first gene therapy for ALS that targets a specific genetic cause of the disease linked to mutant SOD1 proteins.
- A thorough literature review shows that with new drugs like tofersen, there's promising progress in monitoring and potentially slowing ALS's progression.
$100 - $150
Hourly Rate
Effects of tofersen treatment in patients with -ALS in a "real-world" setting - a 12-month multicenter cohort study from the German early access program.
London, UK
2 hours ago
1 Received
- - In April 2023, tofersen, an antisense oligonucleotide, was FDA-approved for treating ALS after it significantly reduced levels of neurofilament light chain (NfL), a marker of neurodegeneration.
- - A follow-up study involving 24 ALS patients in Germany showed that while ALS functional scores declined, there was a notable reduction in both serum NfL and phosphorylated neurofilament heavy chain (pNfH) levels in the cerebrospinal fluid (CSF).
- - The therapy was considered safe, with no ongoing symptoms, despite some patients showing signs of immune response in the CSF, pointing to potential autoimmune reactions.
$100 - $150
Hourly Rate
Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1 ALS mouse model.
London, UK
2 hours ago
1 Received
- Antisense oligonucleotides (ASOs) were the first to successfully target and reduce mutant SOD1 expression in amyotrophic lateral sclerosis (ALS) therapy.
- Short interfering RNAs (siRNAs) also offer a gene-silencing mechanism but faced delivery challenges to the central nervous system (CNS).
- The study introduces a new siRNA-ACO conjugate that enhances delivery to CNS tissues, showing promising results in slowing ALS progression and improving motor function in SOD1 mice.
$100 - $150
Hourly Rate
Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.
London, UK
2 hours ago
1 Received
- Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disease that progressively damages motor neurons in the central nervous system, leading to muscle weakness and eventual paralysis.
- The FDA has approved seven medications for ALS treatment, including Qalsody, Relyvrio, and Radicava, each with unique mechanisms to alleviate symptoms and slow disease progression.
- Despite available treatments, finding a cure for ALS is still very challenging, highlighting the need for ongoing research to better understand the disease and develop effective therapies.
$100 - $150
Hourly Rate
Myelitis as a side effect of tofersen therapy in SOD1-associated ALS.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Inhibition of survivin by 2'--methyl phosphorothioate-modified steric-blocking antisense oligonucleotides.
London, UK
2 hours ago
1 Received
- Chemically modified antisense oligonucleotides (ASOs) have been proven effective in treating various diseases, with ten approved ASO drugs currently on the market, mainly for conditions other than cancer.
- Researchers have developed steric-blocking ASOs that specifically target a known oncogene, initially screening seven candidates in HepG2 cells and identifying ASO-2 and ASO-7 as the most effective in reducing mRNA levels.
- Further testing demonstrated that ASO-7 not only inhibited mRNA expression in a dose-dependent manner but also significantly reduced survivin protein levels, suggesting its potential as a therapeutic BIRC5 inhibitor.
$100 - $150
Hourly Rate
[SOD1 gene therapy delays ALS disease progression].
London, UK
2 hours ago
1 Received
- The patient has familial amyotrophic lateral sclerosis (ALS) linked to a harmful mutation in the SOD1 gene and joined a gene therapy trial in 2020.
- Before treatment, the patient showed significant neurological damage, with an ALSFRS-R score of 41 and elevated CSF neurofilament levels indicating ongoing neuronal injury.
- After four years of receiving tofersen, an antisense oligonucleotide treatment, the patient's condition stabilized, maintaining mobility and a social lifestyle, marking the first successful intervention of its kind in Sweden.
$100 - $150
Hourly Rate
[Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis].
London, UK
2 hours ago
1 Received
- - Amyotrophic lateral sclerosis (ALS) is a serious, incurable neurological disease, with current treatment options limited to palliative care and a few medications that have low efficacy.
- - There are ongoing efforts to develop ALS therapies focusing on gene therapy, stem cells, immunomodulators, and substances targeting gut microbiota, as well as exploring neuroprotective and antioxidant compounds.
- - Future advancements may include prevention strategies through the identification of biomarkers to detect ALS in its early stages before symptoms appear.
$100 - $150
Hourly Rate
Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade.
London, UK
2 hours ago
1 Received
- * The most notable success is nusinersen for SMA, which improves symptoms and slows progression, while tofersen is aimed at ALS but hasn't shown benefits for all patients.
- * This review summarizes current ASO research in MNDs, highlighting both successful and unsuccessful outcomes, discussing the strengths and weaknesses of existing studies, and suggesting future research directions for better treatments.
$100 - $150
Hourly Rate
Current neuroprotective therapies and future prospects for motor neuron disease.
London, UK
2 hours ago
1 Received
- * Advancements in understanding the biology of MND have led to the development of targeted therapies and improved strategies for evaluating new treatments through biomarkers and better clinical trial designs.
- * Although current treatments have only shown to slow disease progression, early intervention using genetic indicators might allow for personalized medicine approaches that could significantly improve outcomes for some patients in the future.
$100 - $150
Hourly Rate
Profiling tofersen as a treatment of superoxide dismutase 1 amyotrophic lateral sclerosis.
London, UK
2 hours ago
1 Received
- Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder that often leads to death within 3-5 years due to respiratory issues, with SOD1 mutations affecting about 2% of patients.
- Tofersen is a new antisense oligonucleotide drug specifically designed to treat patients with SOD1-ALS, and the review discusses its pharmacological properties and clinical trial results.
- Although the VALOR study did not achieve its primary goal, it showed promising results in lowering plasma neurofilament light chain (NfL) levels, indicating potential biomarkers for early treatment in ALS, which will be further explored in the upcoming ATLAS study.
$100 - $150
Hourly Rate
RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.
London, UK
2 hours ago
1 Received
- Amyotrophic lateral sclerosis (ALS) is a deadly neurodegenerative disease, with a significant percentage of familial and sporadic cases linked to mutations in the SOD1 gene, which is toxic to motor neurons.
- The FDA recently approved tofersen, an antisense oligonucleotide (ASO) that targets SOD1, but there is room for improvement in its effectiveness.
- Researchers developed a new type of siRNA (di-siRNA) that shows better results in silencing SOD1 expression, extending survival in ALS mice, and having the potential to treat other similar neurological disorders.
$100 - $150
Hourly Rate
Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.
London, UK
2 hours ago
1 Received
- * PB-TUDCA, one of these treatments, has shown promise in addressing various biological issues related to ALS in clinical trials, particularly in the Phase 2 CENTAUR trial, which indicated improvements in patient outcomes.
- * However, the more recent Phase 3 PHOENIX trial presented contrasting results, showing no significant benefits, leading to the decision to withdraw marketing authorizations for PB-TUDCA from FDA and Health Canada.
$100 - $150
Hourly Rate
Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.
London, UK
2 hours ago
1 Received
- - Antisense oligonucleotides (ASOs) are single-stranded nucleic acids that specifically target RNA and have been approved by the FDA for various diseases, utilizing three main mechanisms of action: mRNA degradation, exon skipping, and mRNA function inhibition.
- - ASOs are structurally modified for stability and resistance to degradation, and examples include drugs like inotersen for hereditary transthyretin amyloidosis and nusinersen for spinal muscular atrophy.
- - The design of ASOs is largely based on mRNA sequence knowledge, making the development process quicker compared to traditional protein-targeted drugs, which enhances their potential for therapeutic applications.
$100 - $150
Hourly Rate