A Multicentre, Randomised, Double-blind, Placebo-controlled and Open Label Extension Study to Assess the Efficacy, Safety, and Pharmacokinetic Profile of of ATL1102 in Non-ambulatory Participants With Duchenne Muscular Dystrophy

This Phase IIb study is a two part, multicenter study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of ATL1102 in non-ambulant boys with Duchenne Muscular Dystrophy aged 10 to <18 years old. The study includes a randomised, double-blind, placebo-controlled treatment period (Part A), followed by an open labelled treatment period (Part B).

开始日期2023-05-18

申办/合作机构

Percheron Therapeutics Ltd.

EUCTR2022-003065-38-BG / Unknown status临床2期

A multicentre, randomised, double-blind, placebo-controlled and open label extension study to assess the efficacy, safety, and pharmacokinetic profile of two dose levels of ATL1102 administered by subcutaneous injection in non-ambulatory participants with Duchenne Muscular Dystrophy

开始日期2023-04-13

申办/合作机构-

ACTRN12618000970246 / Completed临床2期

A Phase 2 open label, study to determine the safety, efficacy and pharmacokinetic profile of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne Muscular Dystrophy.

开始日期2018-08-28

申办/合作机构-

100 项与 ATL-1102 相关的临床结果

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100 项与 ATL-1102 相关的转化医学

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100 项与 ATL-1102 相关的专利（医药）

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项与 ATL-1102 相关的文献（医药）

2015-01-06·Neurology

CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS

作者: Lippincott Williams Wilkins

In the article “CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS” by V. Limmroth …

2014-11-11·Neurology1区 · 医学

CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS

1区 · 医学

Article

作者: Barkhof, Frederik ; Limmroth, Volker ; Desem, Nuket ; Diamond, Mark P. ; Tachas, George

OBJECTIVE:

This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).

METHODS:

In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.

RESULTS:

A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo (p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.

CONCLUSIONS:

In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders.

CLASSIFICATION:

This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.

PloS one3区 · 综合性期刊

Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis

3区 · 综合性期刊

ReviewOA

作者: Summers, Jessica ; Ferizovic, Nermina ; Jiang, Joel ; Buesch, Katharina ; de Zárate, Igor Beitia Ortiz ; Landfeldt, Erik ; Werner, Christian

Background:

Duchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM).

Results:

Our search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes.

Conclusion:

This study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population.

项与 ATL-1102 相关的新闻（医药）

2022-08-22

·GlobeNewswire-Health Care

Long COVID-19 study identifies novel blood markers as potential diagnostic and therapeutic targets

World first study utilizing Somalogic SomaScan® assay# to assess up to 7,000 plasma proteins in Long COVID-19 patients has elucidated novel blood markers as potential diagnostic and therapeutic targetsProvisional patent applications have been filed in the United States (US) to seek protection for these new inventionsA potential therapeutic marker known to be modulated by ATL1102 in DMD patients has been identified as suggestive of its therapeutic potential as a treatment for Long COVID-19Collaboration with global leader in the clinical research of neurological aspects of Long COVID-19 Dr Koralnik to continue with application for grant fundingCompany plans to review its new patent applications with targeted pharmaceutical and diagnostic companies for potential commercial discussions New York, NY, Aug. 22, 2022 (GLOBE NEWSWIRE) -- Antisense Therapeutics Limited [ASX: ANP | US OTC: ATHJY | FSE: AWY] (the Company) is pleased to advise of outcomes from its collaboration to study the neurological aspects of Long COVID-19 (Long Neuro COVID-19) with US based researchers led by global leader in the field, Dr Igor Koralnik, at the Northwestern Medicine Neuro-COVID clinic in Chicago, USA. The study has elucidated novel blood markers as potential diagnostic and therapeutic targets in the treatment of Long COVID-19 patients. Three (3) provisional patent applications have been filed in the US to seek protection for these new inventions.* Under the collaboration, blood samples that had been collected from Long COVID-19 patients who had not been hospitalized (focused on those with neurological symptoms including brain fog, where blood immune cell changes were observed1), were used to generate data on up to 7,000 proteins in the blood utilising a large-scale protein analysis known as proteomics. Industry leading proteomics group Somalogic in Boulder Colorado USA undertook the analysis, successfully testing the samples using their SomaScan® assay and then the data was statistically analyzed using their Dataviz program2. The analyzed data has identified a number of proteins that are significantly modulated in the blood of Long Neuro COVID-19 patients when compared to convalescent subjects who had recovered from Long COVID-19 infection with no persistent symptoms and to healthy subjects. This data has been included in recently filed patent applications as potential diagnostic and therapeutic targets for the treatment of Long COVID-19. Certain targets when combined (as few as 5) identified all 48 Neuro Covid-19 patients and the 42 of 44 subjects who were convalescent or healthy controls suggestive of these targets’ diagnostic potential. A number of targets (<15) have been identified as potentially amenable to treatment by currently available drugs or other therapeutic approaches on the market. The mechanisms of action of those drugs are known to modulate the discovered target proteins, therefore the marketers/developers of those drugs have been identified as initial prospects for partnering interest. A smaller number of diagnostic markers have been detected that could assist in the identification of Neuro Long Covid patients for better designed clinical trials and potentially for earlier treatment intervention. Accordingly, the Company also plans to review its newly generated intellectual property (IP) with targeted pharmaceutical and diagnostic companies for potential commercial discussions, noting that for these discussions to progress, the Company and potential partner companies would need to agree on licensing and/or joint development of this newly generated IP to advance as either diagnostic or therapeutic programs. Of the 94.7 million people in the US diagnosed as infected and surviving COVID-193, approximately 82 million (87%) people are non-hospitalized4, and 45% of non-hospitalized patients5 have developed some manifestation of Long COVID-19 syndrome which suggests more than 24 million people are afflicted by the condition to some extent. The main neurological symptom is brain fog (defined with the established memory tests conducted) and reported in 81% suggesting an impact on nearly 20 million people in the US. Identification of appropriate biomarkers of Long COVID-19 have proved elusive.6 The National Institute of Health (NIH) in the US is funding a national research effort focused on understanding and treating Long COVID-19 beyond US$1billion it has already committed.7 One of the aims of the proteomics analysis was to assess if Neuro Long COVID-19 patients may have been amendable to treatment with ANP’s immunomodulatory drug ATL1102 which has previously demonstrated biologic activity in MS patients11 and the ability to reduce T cells and modulate proteins involved in the blood of DMD patients (data presented at the 2021 World Muscle Society conference WMS-ATL1102-DMD-PROTEOMICS-Poster). Encouragingly, one of the potential therapeutic markers in Long COVID-19 patients identified from this proteomics analysis is also known as having the potential to be significantly modulated by ATL1102 in DMD patients and therefore is suggestive of its therapeutic potential in Long COVID-19. The Company is looking to further explore the clinical potential of ATL1102 in this setting via applying for grant funding opportunities (such as that as offered by NIH) in collaboration with Professor Koralnik. Dr Koralnik said, “The collaboration with Antisense Therapeutics has generated promising novel data in Long COVID-19 patients in identifying potential disease biomarkers and represents an important advance towards the goal of establishing effective disease diagnostics and interventional treatments. We look forward to continuing our scientific collaboration with Antisense Therapeutics and to advancing such endeavors through our active involvement and support in seeking grant applications including with bodies such as the NIH.” Dr George Tachas Director of Drug Discovery at Antisense Therapeutics said, “We are delighted to report on the initial outcomes from this novel and leading scientific collaboration with Professor Koralnik and his team. Our data has identified potential new avenues towards diagnoses and treatment of a disease that has negatively impacted the lives of over a hundred million people around the world. We look forward to continuing scientific advancements in the space in collaboration with Professor Koralnik and the further important IP that we anticipate emerging from this important scientific collaboration.” For further details please refer to the presentation following this announcement. This announcement has been authorised for release by the Board. For more information please contact: Antisense TherapeuticsInvestment EnquiriesUS/European IR &PRMark DiamondGennadi KoutchinLaine Yonker/Joe GreenManaging DirectorXEC PartnersEdison Investor Relations+61 (0)3 9827 8999gkoutchin@xecpartners.com.aulyonker@edisongroup.comwww.antisense.com.au1300 932 037+1 646-653-7035 # ANP is the first Company to utilize Somalogic’s proprietary SomaScan® assay for the analysis of plasma proteins in Long COVID-19 patients. The SomaScan® assay is ‘the first and only platform that can simultaneously measure 7,000 proteins across a wide range of concentrations’. https://somalogic.com/ * Patent application names: “Biomarkers and Uses thereof” “Methods for treating neurological post-acute sequelae of COVID-19 (NPASC)” “Methods for diagnosing and treating neurological post-acute sequelae of COVID-19 (NPASC)” About Antisense Therapeutics Limited [ASX:ANP | US OTC:ATHJY | FSE:AWY], is an Australian publicly listed biotechnology company, developing and commercializing antisense pharmaceuticals for large unmet markets in rare diseases. The products are in-licensed from Ionis Pharmaceuticals Inc. (NASDAQ: IONS), an established leader in antisense drug development. The Company is developing ATL1102, an antisense inhibitor of the CD49d receptor, for Duchenne muscular dystrophy (DMD) patients and reported highly promising Phase II trial results. ATL1102 has also successfully completed a Phase II efficacy and safety trial, significantly reducing the number of brain lesions in patients with relapsing-remitting multiple sclerosis (RRMS). About ATL1102 ATL1102 is an antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4). Antisense inhibition of VLA-4 expression has demonstrated activity in a number of animal models of inflammatory disease. ATL1102 has also shown to be very effective in reducing inflammatory brain lesions in patients with MS (Limmroth, V. et al Neurology, 2014; 83(20): 1780-1788) and recently delivered highly promising clinical results in patients with Duchenne muscular dystrophy (DMD) a rare and fatal muscle wasting disease where inflammation in the muscle leads to fibrosis and death of muscle tissue. About Long COVID-19 In the US of the first 80 million people diagnosed as infected and surviving COVID-193, approximately 30% of hospitalized patients9 and 45% of non-hospitalized patients5 have developed some manifestation of Long COVID-19 syndrome (i.e more than 24 million people). According to the US Centre for Disease Control and Prevention “Post-COVID conditions are associated with a spectrum of physical, social, and psychological consequences, as well as functional limitations that can present substantial challenges to patient wellness and quality of life”.10 Confirmed infections numbers which increases daily can be followed on these links below3. Long COVID-19 cases in Australia were recently estimated at 475,00011. A body of published evidence now demonstrates that the SARS-CoV-2 virus causes long COVID-19 with impacts that last by definition for 28 days post COVID-19 symptom onset1 and that can last for 12 weeks and well beyond9. Long COVID-19 can occur post severe COVID-19, and post mild to moderate COVID-19. In the US Long COVID-19 patients comprise 13% of subjects post severe COVID-19 who have previously being hospitalized and 87% of subjects post mild-moderate COVID-19 who have not been hospitalized. In the latter there is ~2:1 ratio of females to males, like in autoimmune disease multiple sclerosis and the main neurological symptoms reported were 81% brain fog (defined with the established memory tests conducted), 68% headache, 60% numbness/tingling 59% dysgeusia, 55% anosmia, and 55% myalgias, and additionally 85% experienced fatigue, which are not well understood.4 While COVID-19 incidence and severity is being reduced with vaccines numerous studies connect the SARS-CoV-2 virus infection to long term neurological conditions in both hospitalized and non-hospitalized patients after vaccination.12 References Visvabharathy L, and Koralnik, I.J et al “Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination.” https://www.medrxiv.org/content/10.1101/2021.08.08.21261763v3https://somalogic.com/stats-data-viz/ and https://somalogic.com/life-sciences/ 7,000 analytes, 450,000+ samples run, >400 publications, >500 patents.https://coronavirus.jhu.edu/map.html and https://www.worldometers.info/coronavirus/country/us/ as of 16 August 2022, 94.7 million people in the USA were diagnosed with COVID-19, 1.063 million deaths have been recorded, and 89.9 million people have recovered.Graham E.L and Koralnik I.J et al. “Persistent neurological symptoms and cognitive dysfunction in non-hospitalized COVID-19 “Long Haulers”. Ann. Clinical and Translational Neurol 2021, 8(5):1073-1085 https://onlinelibrary.wiley.com/doi/epdf/10.1002/can3.51350 Estiri H et al “Evolving phenotypes of non-hospitalized patients that indicated long COVID”. BMC Medicine (2021) 19: 249 https://doi.org/10.1186/s12916-021-02115-0https://www.msn.com/en-us/health/medical/brain-fog-and-other-long-covid-symptoms-can-last-more-than-a-year-according-to-study/vi-AA10gBishttps://www.cbsnews.com/news/long-covid-research-funding/. Limmroth V, Barkhof F, Desem N, Diamond M.P and Tachas G. “CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS”. Neurology, 2014; 83(20): 1780-1788) https://pubmed.ncbi.nlm.nih.gov/25239835/Chen Chen et al “Global prevalence of Post-Acute Sequelae of COVID-19 (PASC) or Long COVID: A meta-Analysis and Systematic Review. https://www.medrxiv.org/content/10.1101/2021.11.15.21266377v1https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-clinical-eval.htmlhttps://www.abc.net.au/news/2022-08-11/long-covid-and-chronic-fatigue-syndrome-pathology-overlap/101318522Ledford H “Do vaccines protect against Long COVID? What the data say”, Vaccines reduce the risk of developing COVID-19- but studies disagree on their protective effect against long COVID. 23November 2021 https://www.nature.com/articles/d41586-021-03495-2“Mass disability event” warning as huge numbers diagnosed with Long Covid” Matt Young https://www.news.com.au/technology/science/human-body/mass-disability-event-warning-as-huge-numbers-diagnosed-with-long-covid/news-story/d541286fc71ac1b2a262ac798238d4ec

疫苗

2022-06-22

·GlobeNewswire-Health Care

New Muscle Disease Indication for ATL1102 – Limb Girdle Muscular Dystrophy R2

LGMDR2, also referred to as dysferlinopathy, is a rare genetic muscle disease caused by mutations in the dysferlin gene (DYSF)Animal study conducted at MCRI in collaboration with Jain Foundation in the USStudy results showed significant decreases in target CD49d RNA and key immune cell RNA levels in the muscleData supports progression into a longer-term efficacy study planned for 3Q/4Q2022 Mark Diamond, Antisense Therapeutics Managing Director and CEO said: “It is exciting for the Company to be announcing a successful scientific exploration into a new muscle disease indication for ATL1102, LGMDR2. This was a strategically minded move on behalf of the Company to capitalise on the extensive data package generated to date on ATL1102 and to broaden ANP’s product pipeline. Similar to DMD, this is a rare muscle disease with a clear need for an effective treatment as emphasised by our expert consultants in the field. The results achieved in this first LGMDR2 animal study are showing the requisite effects on targeted immune cells. Having demonstrated target activity in a dysferlin animal model gives us confidence to advance the program in LGMDR2 and consider other muscle diseases with immune cell involvement as the data continues to point to the broader potential of ATL1102 as a treatment for such conditions.” New York, NY, June 22, 2022 (GLOBE NEWSWIRE) -- Antisense Therapeutics Limited [ASX:ANP | US OTC:ATHJY | FSE:AWY] today announced the results from a first study of antisense to CD49d in a limb girdle muscular dystrophy R2 (LGMDR2) mouse model. LGMDR2 is a rare genetic muscle disease that is caused by mutations in the dysferlin gene that leads to significant reduction or absence of dysferlin protein levels in muscle fibers. Dysferlin loss occurs in both males and females with the condition called dysferlinopathy or LGMDR2. LGMDR2 is characterized by muscle inflammation, fibrosis, adiposity (fat) and progressive weakness in the hip and shoulder area (i.e. the limb girdle) proximal muscles (those closest to the center of the body) with loss of ambulation and upper limb function in adulthood. LGMDR2 affects ~ 1 in 125,000 people.1,2,3 There are no disease modifying agents in advanced development and no treatments have proven to be beneficial to slow the progression of the disease. This first study of antisense to CD49d in the LGMDR2 mouse model (Bla/J mice with dysferlin loss) was undertaken in collaboration with experts in genetic muscle disease at the Murdoch Children’s Research Institute (MCRI) in Melbourne and the Jain Foundation in the USA. The Jain Foundation (https://www.jain-foundation.org/), a non-profit disease foundation established in the hopes of curing dysferlinopathy, is coordinating the worldwide efforts to find a treatment for dysferlinopathy and have substantial experience with LGMDR2. In the study, Bla/J mice were treated with an antisense oligonucleotide (ASO) to CD49d at three dose levels (5, 10 and 20mg/kg) once weekly for six weeks, with a corresponding negative control oligonucleotide at the same dose levels. The study also included untreated Bla/J mice and healthy mice as controls. The results showed that at the low 5mg/kg/week ASO dose, the RNA levels of CD49d, and CD8 T cells and F4/80 macrophage cells in the quadricep muscle were significantly decreased by 42%, 86% and 70% respectively, compared to the levels observed in the mice dosed at the 5mg/kg/week dose level of the control oligonucleotide (P<0.05 Fisher’s Least Significant difference test). A significant reduction in CD8 RNA vs the untreated control Bla/J was also observed (see Figure 1 below). Notably, in the quadricep muscle of the female untreated control mice, there was 2.5 times more F4/80 RNA than male mice (data on file). F4/80 is a marker of macrophages which are key immune cells involved in the disease and the increase in these cells is suggestive of a more active disease in the female mice. ASO treatment in female mice achieved significant reduction in F4/80 and CD8 cell mRNA in the quadricep muscle. In these same female mice, a trend towards reduction of 38% (P=0.0656) in CD49d RNA was observed compared to untreated Bla/J in another proximal muscle called the Psoas (see Figure 2 below). Given these observations the next study will be conducted in the female mice as agreed with the experts at the Jain Foundation. The results from this first investigation of the potential of an antisense to CD49d drug in the Bla/J dysferlin deficient mouse model have shown the use of a low dose of the drug reduces the target (CD49d) and key immune cell (F4/80 macrophage and CD8+ T cells) RNA in the muscle. The results support the Company’s plans to move forward with the second phase (chronic setting) of the program with a follow on study in the same mouse model to test the potential of the low dose to reduce adipose (fat) levels, muscle loss and damage. The second study is planned for 3Q/4QCY22 (pending the availability of suitably aged mice) and designed to run for four months, with results to follow shortly thereafter. The use of ATL1102 as a treatment for dysferlinopathy is covered in ANP’s patent application PCTAU2020/050445 directed at modifying muscle performance by reducing muscle adiposity. The recently filed provisional application 2021903024 also claims the use of ATL1102 to reduce thrombospondin-1 reported to be beneficial in treating the disease. The data from Bla/J mice studies can be used to support the prosecution of these claims and the filing of a new patent application. Dr George Tachas Ph.D., Director, Drug Discovery and Patents at Antisense Therapeutics said “We are pleased to be continuing our key scientific collaboration with the MCRI while also benefiting from the expert advice provided by the Jain Foundation. The positive results from this first study in dysferlin deficient mice encourage us to move into the chronic phase of the program and we look forward with great anticipation to the results of this follow on study. There are several genetic muscle diseases with similar immune cell involvement like in LGMDR2 and DMD and so this data points to the potential use of low dose of ATL1102 as a treatment for such conditions.” Laura Rufibach, Co-President of the Jain Foundation, said “With a singularly focused mission to find a cure for dysferlinopathy, we at the Jain Foundation are pleased to be working with Antisense Therapeutics and the MCRI on their research program evaluating the antisense to CD49d drug as a possible treatment of dysferlinopathy. We are encouraged by the results of the first study and look forward to the data of the longer dosing study to assess the efficacy of the treatment in mice in order to determine the potential of ATL1102 to be an effective therapy in this devastating and debilitating disease.” Associate Professor Alastair Corbett, Neurologist at the Concord Repatriation General Hospital Neurology Clinic, said “LGMDR2 is a rare recessive muscular dystrophy with no effective treatment. The disease starts in late adolescence and patients show signs of muscle weakness at 15-30 years of age and it progresses slowly as people live into adult life. Patients exhibit weakness of the shoulder and hip muscles which adversely effects their upper and lower limb function. Sufferers of the disease struggle with mobility with a significant loss of quality of life and ultimately lose ambulation as they become wheelchair bound. Many muscle dystrophies with significant inflammation are in need of more effective therapies. I am very pleased to be involved with the hope that such endeavors may help a population in great need of an effective treatment.” This announcement has been authorised for release by the Board. For more information please contact: Antisense TherapeuticsInvestment EnquiriesUS/European IR & MediaMark DiamondGennadi KoutchinLaine Yonker/Joe Green Managing Director and CEO XEC Partners Edison Investor Relations+61 (0)3 9827 8999 gkoutchin@xecpartners.com.aulyonker@edisongroup.comwww.antisense.com.au1300 932 037+1 646-653-7035 About Limb Girdle Muscular Dystrophy R2 caused by the genetic loss of dysferlin. Limb-girdle muscular dystrophy (LGMD) is a group of rare muscular dystrophies primarily characterized by hip and shoulder (i.e. limb-girdle) proximal muscle weakness estimated to occur as a class in up to 6.9 in every 100,000 people5. Over 30 subtypes have been identified with different underlying genetic causes. Dysferlin loss occurs in the recessive genetic muscle disorder LGMDR2, formerly known as LGMD2B, and the related muscle disease Miyoshi myopathy dystrophy 1 (MMD1)6 . Collectively these disorders caused by the loss of dysferlin are called Dysferlinopathy 1. Dysferlinopathy (LGMDR2) prevalence is approximately ~ 1 per 125,000 people3 or 2500 people in the US, or 18% of all LGMDs4 with an estimated upper range for LGMDR2 of ~ 4000 people in the US. In LGMDR2, the initial weakness is seen in the proximal muscles and in the case of MMD1 there is initially distal muscle weakness. However, natural history data on dysferlinopathy have shown that LGMDR2 and MMD1 are the same disease6. Dysferlin is a transmembrane protein that has been shown to be involved in multiple cellular processes such as calcium regulation, membrane repair, and membrane trafficking. The absence of dysferlin in LGMDR2 is characterized by activated F4/80 macrophage and T cell inflammation and increase in fat replacing the muscle, where adipocytes replace dysferlin deficient muscle, as detected by MRI. This progressively reduces muscle strength, ability to walk, reduces upper limb function and quality of life.5 There are currently no treatments for dysferlinopathy. The steroid drug deflazacort treatment failed in a 6 month patient study and made the disease worse. Deflazacort (1mg) taken for a month, every second day for 5 months reduced muscle strength, which reversed after cessation of steroid treatment7. There is an unmet need for effective therapies so that people with LGMDR2 can maintain ambulation, muscle strength and quality of life. References https://www.jain-foundation.org/https://www.jain-foundation.org/research/dysferlin-background/therapeutic-opportunities/Liu W et al Genetics in Medicine 21 2512-2520 (2019) Estimates 0.75 per 100000 https://www.nature.com/articles/s41436-019-0544-8Moore et al J Neuropathol Exp. Neurol 2006 65(10): 995-1003 https://academic.oup.com/jnen/article/65/10/995/2646712https://rarediseases.org/rare-diseases/limb-girdle-muscular-dystrophies/https://pubmed.ncbi.nlm.nih.gov/33610434/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617000/ The study results in the psoas muscles above suggest target CD49d RNA knockdown when CD8+ and F4/80+ cells remain in the female psoas muscle. In the quadricep muscles the target CD49d knockdown is less visible as the CD8+ and F4/80+ cells that express CD49d are substantially reduced (by 86% and 70% respectively) so there are less cells remaining to observe a statistically significant reduction versus untreated control mice. Attachments Figure 1 Figure 2

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100 项与 ATL-1102 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
杜氏肌营养不良症	临床2期	澳大利亚	Percheron Therapeutics Ltd.	2023-05-18
杜氏肌营养不良症	临床2期	保加利亚	Percheron Therapeutics Ltd.	2023-05-18
杜氏肌营养不良症	临床2期	塞尔维亚	Percheron Therapeutics Ltd.	2023-05-18
杜氏肌营养不良症	临床2期	土耳其	Percheron Therapeutics Ltd.	2023-05-18
杜氏肌营养不良症	临床2期	英国	Percheron Therapeutics Ltd.	2023-05-18
多发性硬化症	临床2期	罗马尼亚	Percheron Therapeutics Ltd.	2006-01-02
干细胞动员	临床1期	澳大利亚	Percheron Therapeutics Ltd.	-
眩晕	临床1期	澳大利亚	Percheron Therapeutics Ltd.	-
哮喘	临床前	澳大利亚	Percheron Therapeutics Ltd.	-
肿瘤	临床前	美国	-	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


MDA2024	N/A	-	-	ATL1102 25mg s.c.	艱遞鹹觸築鹽餘廠願積(築鏇窪齋醖構糧鑰壓淵) = 積襯繭顧憲選鑰觸醖餘鑰憲憲衊醖衊遞簾簾簾 (壓窪鹹醖鑰遞積築窪積 ) 更多	-	2024-03-03