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Sanfilippo B

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  1. flosz 19 september 2015 15:53
    Hoogste tijd imho voor een Sanfilippo B draad.

    Positive Topline Results Announced from Phase I/II Trial in Sanfilippo B Syndrome Patients Using uniQure’s Novel AAV5-Based Gene Therapy

    --Safety, Durable NaGlu Protein Expression and Positive Signs of Efficacy Demonstrated in All Four Patients--
    --First Clinical Validation of AAV5 Vector Effectively Delivering Target Gene into the CNS--
    --Company Intends to Advance Program into Pivotal Stage--
    --Conference Call to Discuss Data Scheduled for 8:30 am EDT Monday, September 21--

    Amsterdam, the Netherlands, September 19, 2015 —uniQure N.V. (Nasdaq: QURE), a leader in human gene therapy, today announced the topline results of one-year follow-up data from a Phase I/II clinical trial conducted by Institut Pasteur (Biotherapies for Neurodegenerative Diseases Unit, Institut Pasteur/INSERM) in partnership with the French Muscular Dystrophy Association and Vaincre les Maladies Lysosomales (collectively “the consortium”) in four Sanfilippo B syndrome (MPSIIIB) patients treated with a novel gene therapy, AMT-110. In all four patients, researchers verified the restoration of catalytical activity of the NaGlu protein in the cerebrospinal fluid (CSF) from 0% at baseline up to 14-17% of normal at 3 months with persistent effect at 12 months. These results validate the effective transmission of the NAGLU gene with the AAV5 vector. The trial demonstrated that incremental cognitive development was maintained in all four patients, aged 20 to 53 months at study onset. The therapy consists of uniQure’s proprietary AAV5 viral vector and a gene cassette including the N-acetylglucosaminidase, alpha (NAGLU) gene, manufactured with uniQure’s proprietary insect cell based-technology. The results of the trial were presented on September 19th at the European Society of Gene and Cell Therapy (ESGCT) and Finnish Society of Gene Therapy (FSGT) Collaborative Congress held in Helsinki, Finland, by Dr. Marc Tardieu, Professor at the Université and Hôpitaux Universitaires Paris Sud and primary investigator of the trial with co-investigators Professors Jean-Michel Heard and Michel Zérah.??“We are forging new ground in the treatment of Sanfilippo B with this study. For the first time we have shown persistent restoration of NaGlu protein expression over 12 months can be achieved with gene therapy in the CNS,” said Professor Tardieu. “Published case studies of attenuated Sanfilippo B patients support that NaGlu protein activity in the range of 5-10% of normal can be considered clinically meaningful and is associated with longer lifespans and higher quality of life for Sanfilippo B patients. We look forward to further confirming these encouraging trends on cognitive development over the next 6-12 months.”
    In the trial, four patients received a one-time administration of AAV5 gene therapy dosed over two hours directly into the brain. All patients were maintained under coverage of a continuous immune suppression regimen. No local inflammation or other safety concerns related to the therapy or the procedure have been identified. In addition to establishing the safety of the procedure and the AAV5 viral vector, the most important result was the presence of catalytically active NaGlu protein in the CSF measured at 1, 3, and 12 months after treatment. The fact that all treated Sanfilippo B subjects continued to gain skills throughout the study is extremely encouraging.
    “We are gratified that our pursuit of a gene therapy targeting CNS diseases has found this early and promising success. The data validates AAV5 from our insect cell-based manufacturing platform as a safe and effective vector choice for CNS administration. Based on these results, we are negotiating an agreement with the consortium to take over the sponsorship of the program and we intend to advance the program into the pivotal stage of development. We acknowledge the tremendous support we have received from the consortium that was paramount for generating this early proof in patients,” said Joern Aldag, CEO of uniQure. “Sanfilippo B syndrome represents a high unmet medical need and we are committed to developing a gene therapy that can improve and extend the lives of patients and making it available to them and their families worldwide as soon as possible.”

    About Sanfilippo B?Sanfilippo B is a rare inherited lysosomal storage disease that results in serious brain degeneration in children and is generally fatal. The disease stems from an enzyme deficiency caused by a malfunctioning NAGLU gene.  Due to the inability to properly break down long chains of sugar molecules called mucopolysaccharides or glycosaminoglycans (GAGs) that are a normal by-product of cell metabolism, the cells accumulate partially degraded oligosaccharides of heparin sulfate, which are molecules that regulate various developmental processes. The clinical manifestations of the disease are mainly neurological with early symptoms observed during the first 5 years of age, leading to a progressive deterioration of cognitive abilities.  Affected children begin developing cognitive symptoms at around 2 years of age, proceeding to a precipitous neurological decline with behavioral, sleep and social difficulties between the ages of 4 and 7. Further profound mental retardation ensues, with death occurring around age 17. No proven disease modifying treatments for Sanfilippo B are currently available.

    Conference Call and Webcast?uniQure will discuss the data in a webcast conference call at 8:30 am EDT on Monday, September 21, 2015. The conference call can be accessed by dialling one of the numbers listed below five minutes prior to the start of the call and providing the confirmation code: 3342119.
  2. flosz 19 september 2015 16:10
    Uit draad

    Int.Conference Sanfilippo Syndrome and Related Lysosomal Storage Diseases, Geneva, Switserland

    Conference Day 2 Afternoon - Friday 27th November
    13h30-15h00 Session 3 : Specific Clinical Aspects of MPS III and New Treatment Approaches

    1) Keynote Presentation - Intra-Cerebral Administration of AAV2/5 Vector containing Human NAGLU cDNA in Children with

    MPS IIIB : Results at 12 months of a Phase I/II trial

    Prof. Marc Tardieu, Paediatric Neurology Service, INSERM, Unit 1012, University Paris-South, France


    Abstract: zie bijlage.


    Oud, 2008:


    Linkje trial:
  3. flosz 19 september 2015 16:11

    June 23, 2015
    Zack Fink

    This week I have been giving some thought to the Sanfilippo B gene therapy program (AMT-110) that uniQure has rights to in-license from Institut Pasteur. With AMT-110 data expected within the next 6 months, I decided it would be prudent to give a brief overview of gene therapy for lysosomal storage diseases, especially with Plasmatech Pharmaceuticals (PTBI) completing their reverse merger with the private gene therapy company Abeona Therapeutics (ABEO) last week.

    Lysosomal Storage Disease Overview

    Lysosomal storage diseases (LSDs) are inherited metabolic storage diseases characterized by progressive accumulation of undigested materials in the lysosomes of affected cells – a consequence of a genetic defect resulting in missing/improperly functioning digestive enzyme(s). LSDs are an ideal class of disorders to target with gene therapy due to their monogenic nature and clearly defined biology. Further, modest enzymatic activity may be sufficient for clinical efficacy in storage disease with CNS involvement – see Bluebird’s Adrenoleukodystrophy data [1,2]. LSDs with central nervous system (CNS) involvement are the first group of LSDs to be treated with gene therapy most likely because of the poor existing standard of care – limited protein replacement therapy (ERT/SRT) and hematopoietic stem cell transplantation (HSCT). A comparison of the advantages and disadvantages of each therapeutic option for LSDs can be seen below, along with a table of LSDs treated with ERT such as Shire’s (SHPG) Elaprase (idursulfase) and Sanofi/Genzyme’s (SNY) Aldurazyme (lardonidase) [3]:

    Protein replacement therapies tend to be ineffective for the CNS disease in LSDs because of their inability to cross the blood-brain barrier. In order to promote transgene expression in the CNS, in-vivo gene therapy for LSDs with CNS involvement primarily rely on three routes of administration: intravenous delivery (IV), CSF injection, or direct injection into the brain. In addition, ex-vivo gene therapy in these indications rests on traditional HSCT with modified stem cells, resulting in modified progenitor cells migrating to the CNS. There is, however, clinical proof-of-concept data in LSD for CNS involvement in both in-vivo and ex-vivo gene therapy.

    Clinical Proof of Concept for LSD Gene therapy

    In 2013, Biffi et al. were the first to publish clear clinical proof-of-concept data for a gene therapy in an LSD with CNS involvement [4]. Investigators used a lentiviral vector for ex-vivo transduction of stem cells from three patients diagnosed with late infantile metachromatic leukodystrophy (LI-MLD).

    MLD is a caused by mutations in the ARSA gene resulting in buildup of sulfatide in CNS cells, leading to demyelination and neurodegeneration. Late infantile MLD patients present symptoms by their third birthday and usually die within a few years of symptom onset. There are no treatments that substantially delay the progression of MLD.

    In this trial, investigators used a “control group” that consisted of disease progression data from older siblings of the enrollees, who also were diagnosed with LI-MLD. Patients demonstrated above-normal expression of ARSA throughout the hematopoietic cell lineages at one year post-treatment. Importantly, at 18-24 month follow-up all three treated patients had their disease progression halted and/or slowed compared to “controls” and a natural history cohort of untreated LI-MLD patients.

    Despite the immense read-through for the potential of ex-vivo lentiviral gene therapies in other LSDs with CNS involvement, the use of this treatment modality may be limited – the transgene is only expressed in the CNS by cells with hematopoietic lineage, such as microglia. Gene therapy for LSDs rely on individual cells expressing adequate amounts of missing protein to prevent storage buildup. In order to maximize efficacy, transgene expression should be widespread to all cells in the CNS – not just those with hematopoietic lineage. This is why much of the excitement for LSD gene therapy (and CNS gene therapy as a whole) has risen from the use of AAV vectors which have the ability to lead to widespread transduction in the CNS.

    In 2014, Tardieu et al. were the first group to publish clear clinical proof-of-concept data for in-vivo gene therapy of a LSD with CNS involvement [5]. The investigators enrolled four patients diagnosed with Mucopolysaccharidosis Type IIIA (MPSIIIA, Sanfilippo A) and treated these patients with an AAVrh.10 vector carrying the SGSH and SUMF genes. As a reminder, Sanfilippo A is caused by a mutation in the SGSH gene resulting in the typical pathophysiology seen in LSDs with CNS involvement. The investigators delivered a total dose of 7.2E11 vector genomes (vg) per patient at 12 deposits in the brain (via 6 image-guided tracks). Based on neurological and clinical evaluations, three treated patients were considered clinically stable, with the fourth showing improvement, at 52 weeks post-treatment. This contrasts the disease’s natural history.

    Lysogene obtained an exclusive license to develop AAVrh.10-SGSH-SUMF in 2013, and renamed the asset SAF-301. Lysogene is currently conducting a 5-year follow-up study of the original four patients treated with SAF-301 [6].

    Looking into the Future

    With the recent improvement in AAV vector manufacturing and delivery, I’m optimistic that within the next several years future gene therapy trials designed to treat the CNS disease involvement in LSDs could show modest clinical efficacy. These future positive clinical trial data could position gene therapy as a treatment option (not a cure) to add to the treatment arsenal for LSDs.

    Further down the road, novel AAV vectors (via rational design and directed evolution) with improved transgene cassettes are going to be moving into the clinic. These novel AAV vector/transgene cassettes are the future of in-vivo CNS gene therapy – as well as in-vivo AAV gene therapy as a whole.
  4. flosz 19 september 2015 16:12
    UniQure’s (QURE) presentation of 1-year follow-up data from patients with Sanfilippo B (MPS IIIB) and treated with the gene therapy AMT-110 is only a week away, on September 19 (here). Expectations are modest in front of what could be equivocal results for this early product candidate.

    By way of background, AMT-110 consists of an AAV5 vector carrying a therapeutic NaGlu (a-N-acetylglucosaminidase) gene. Institut Pasteur began a phase I/II study in four patients in October of 2013, and this will be the first look at 1-year results. UniQure has an agreement to acquire the clinical results and commercial rights to the program following completion of this small study.

    For a deeper look at QURE, read our previous coverage.

    First, I want to re-emphasize what I stated in a blog post on gene therapies for lysosomal storage diseases last month: that clinical proof-of-concept data does exist for gene therapies in lysosomal storage diseases for both lentiviral vectors (late infantile metachromatic leukodystrophy) and adeno-associated virus (AAV) vectors (Sanfilippo A, MPSIIIA). But, the existing results are not highly indicative.

    Privately held Lysogene tested SAF-301 (AAVrh.10-SGSH-SUMF) in 4 patients diagnosed with Sanfilippo A (MPSIIIA) in an open-label phase I/II trial that began in 2011. With these types of heterogeneous progressive neurodegenerative conditions, long-term follow-up is required to truly understand the treatment effect, if any, thus existing results from the Lysogene program should be viewed as preliminary. At one year post-treatment, investigators determined that patients 1-3 were considered clinically stable, and patient 4 was considered to have improved. In addition, neuropsychological evaluations suggested a possible improvement in behavior, attention, and sleep. Exhaustive neuropsychological evaluations performed at inclusion and 52-weeks post gene transfer are shown below [1]:

    The neuropsychological evaluations used are objective and do not provide a robust efficacy signal with 52-week follow-up. As mentioned, I suspect longer-term follow-up is required to tease out any meaningful cognitive effect. Lysogene continues towards 5-year follow-up of the original four patients treated with SAF-301, but we do have parent testimony on one subject. Karen Aiach, co-founder and CEO of Lysogene, has a diagnosed daughter who received SAF-301 in the phase I/II clinical trial. Mrs. Aiach was interviewed in Forbes in July: “[Ornella] was dosed with treatment at the age of 6, which is pretty advanced in the disease. Since then she’s been much better for the last three years from a behavioral standpoint – not hyperactive, sleeps well. That’s changed her life, and the lives of her family around her” [2]. Nevertheless, an objective signal is somewhat weak, and 5-year follow-up will be critical to determine the robustness of this efficacy.

    Enzyme replacement therapy (ERT) such as Biomarin’s (BMRN) laronidase (MPS I) and Shire’s (SHPG) idursulfase (MPS II) have been the standard-of-care for somatic MPS. Unfortunately, due to CNS involvement in MPS IIIA/B, ERT has not been shown to be effective in these indications, and hematopoietic stem cell transplant (HSCT) has not been adequately assessed for MPSIII.

    In order to determine where investors should place the efficacy hurdle for CNS symptoms and disease course for MPSIIIA/B, we turned to cognitive outcomes for MPS I patients – a type of MPS with CNS-involvement – treated with ERT and HSCT. To date, intravenous ERT for MPS I has not been sufficient to prevent decline or improve cognition in patients with MPS I [4]. HSCT, meanwhile, has been shown to improve disease severity and cognition in patients with MPS I, but It was only after multi-year follow-up that efficacy could be adequately assessed [3,5]. The importance of multi-year follow-up in determining treatment efficacy is further supported by the significant natural history variability in patients diagnosed with MPSIIIA/B [3, 6-8].

    So what does this mean for the impending AMT-110 52-week follow-up data? It’s likely much too early for a robust efficacy signal on the cognitive assessments. Biomarkers are a much more appropriate outcome to asses, such as glycosaminoglycan (GAG) accumulation and NaGlu expression. These may offer validation that the AAV5 vector has successfully transfected cells in the CNS and are functionally active.

    We sat down with uniQure last week to discuss the endpoints being used in this trial. Recall that the Pasteur group that conducted the Lysogene SAF-301 trial are the same group conducting the AMT-110 Sanfilippo trial, and they will be using the same cognitive and neuropsychological endpoints that were assessed in the Lysogene trial: Psychoeducational Profile (PEP-3), Vineland adaptive behavior scale (Vineland-II), and Toddler Behavior Assessment Questionnaire (TBAQ). GAG accumulation will not be assessed in this trial because the Pasteur group was unable to develop an adequate assay to measure GAG. UniQure stated if they do in-license the program they will work on developing a validated assay for GAG measurement.

    Upside in Uniqure Stock?
    Put directly, I don’t expect a robust cognition efficacy signal at the 52-week follow-up. I would, however, be satisfied with these results suggesting CNS disease stabilization, as seen in the SAF-301 trial. Despite AMT-110 being dosed five times higher than SAF-301, the AAV5 vector appears to be inferior to the AAVrh.10- vector for CNS applications [9-12]. Despite this, there is reason to believe that AMT-110 could show a cognitive/neuropsychological efficacy signal considering that the AMT-110 trial enrolled much younger patients (2-4 years old) than those dosed in the SAF-301 trial (5-6 years old). In addition, AMT-110 was delivered via 8 burr holes, which includes delivery to the cerebellum. SAF-301 was delivered via 6 burr holes and excluded the cerebellum.

    In terms of AMT-100’s potential value, upside (or downside) is difficult to quantify. First, multi-year follow-up are absolutely necessary to determine who should be administered these gene therapies and when in their disease progression. This was highlighted with laronidase, where a robust efficacy signal was only apparent after six-years of follow-up [13]. In attempting to quantify potential sales, we turned to revenue numbers from Shire’s Elaprase (idurasulfase). We calculated a current worldwide market penetration of idurasulfase in MPS II of ~20%. For simplicity sake, we assume a similar, aggressivemarket penetration for AMT-110; but, we also assume only 40% of patients will be eligible for AAV5 gene therapy due to pre-existing neutralizing antibodies. With a one-time WAC of $800k, U.S./EU sales peak in the $200 million-range. Using these assumptions, we feel comfortable with current available data assigning a maximum fundamental upside of ~$4.00/share for Uniqure, with a 33% probability of success and a 20% discount rate. Of note, the 33% probability of success is our pre-data estimate and assumes that AMT-110 will show a similar modest cognitive/neuropsychological signal as SAF-301.

    Perhaps more importantly, these AMT-110 results may give investors a better idea of gene therapy’s applicability in lysosomal storage diseases, a fairly broad, unmet orphan need. Success now, or further down the road, opens the opportunity in a number of CNS-driven LSDs.

  5. flosz 19 september 2015 16:21
    Clinical trial launched to treat Sanfilippo B syndrome using gene therapy

    Nov 28, 2013

    A phase I/II gene therapy clinical trial for children suffering from Sanfilippo B syndrome, a rare genetic disease, enrolled a first patient in October of this year.

    The trial is being carried out and coordinated by the Institut Pasteur (the trial’s sponsor), Inserm, AFM-Téléthon and Vaincre les Maladies Lysosomales (VML). It is being conducted at Bicêtre Hospital (AP-HP) in Paris. If the treatment is successful it will pave the way towards the development of other gene therapy treatments using the same process.
    Sanfilippo syndrome is a rare genetic disease (also referred to as an orphan disease) that affects approximately 1 in 100,000 children. It is caused by a gene mutation that affects lysosomes – organelles that play essential roles in cell functions – including digestion and protein recycling mechanisms. The first symptoms of the disease – hyperactivity, speech disorders - arise at roughly 2 years of age and lead to neurodegeneration, progressive hearing loss, gradual loss of autonomy and premature death, in most cases before the age of 20. There is currently no cure or treatments available to address either the symptoms or the progression of the disease.

    This clinical trial is the result of 10 years of collaborative research* carried out by Professor Jean-Michel Heard and his team at the Institut Pasteur (Biotherapies for Neurodegenerative Diseases Unit, Institut Pasteur/Inserm U1115) in partnership with AFM-Téléthon and Vaincre les Maladies Lysosomales (VML). It is based on the development of a viral vector capable of delivering one of the four potentially mutated genes in Sanfilippo patients (corresponding to four essential lysosomal enzymes) to the patient’s brain cells. This trial focuses on the B form of the disease. Cells incorporate the missing gene, provided by the viral vector, into their DNA thus enabling them to produce the missing enzyme.

    The treatment consists of several intracerebral vector deposits in several areas of the brain. It was administered to the first patient in October 2013 by Professors Marc Tardieu, from the pediatric neurology department at Bicêtre Hospital (AP-HP), and Michel Zerah, from the pediatric neurosurgery center at Necker Hospital (AP-HP). Scientists and medical professionals consider that the patient’s very young age – two and a half years old –increases the chances of the therapy’s success. Three other children will be enrolled into the trial over the coming months thanks to the cooperation and support of Vaincre les Maladies Lysosomales (VML).

    The original construction of the viral vector, produced by the company uniQure, uses innovative technology which enables batches to be manufactured with a high level of purity. Because of this, the process is already compatible for large-scale use. uniQure was chosen as a partner because it is the first company to receive market approval in Europe for a gene therapy treatment, Glybera®.

    Due to the slow progression of Sanfilippo syndrome, benefits of the treatment on the natural progression of the disease will not be appreciated before several years. This trial, if successful, could also open the door to future applications of the viral vector in gene therapy treatments, particularly in the treatment of neurodegenerative diseases.

    Institut Pasteur, sponsor

    Louis Pasteur created the Institut Pasteur in 1887 as a private non-profit foundation that rapidly became world-renowned for its biomedical research. The main aim of the Institut Pasteur is understanding and preventing diseases throughout the world through excellent scientific and public health research, teaching and other activities. Together with its major contribution to a deeper understanding of fundamental aspects of life, the Institut Pasteur continues to devote a large part of its efforts to infectious diseases, inherited disorders, neurodegenerative diseases and certain cancers. Close to 2,600 people work on its main campus in Paris, which is at the heart of an international network of 32 research institutes on 5 continents. Over the years, 10 Institut Pasteur researchers have received the Nobel Prize.


    Founded in 1964, the French National Institute of Health and Medical Research (Inserm) is a public scientific and technological institute which operates under the joint authority of the French Ministry of Health and French Ministry of Research. The mission of its scientists is to study all diseases, from the most common to the most rare, through their work in biological, medical and public health research. Inserm supports more than 300 laboratories across France. In total, the teams include nearly 13,000 researchers, engineers, technicians and administrative staff, etc. Inserm is a member of the National Alliance for Life and Health Sciences, founded in April 2009 with CNRS, Inserm, the CEA, INRA, INRIA, the IRD, the Pasteur Institute, the Conference of University Presidents (CPU) and the Conference of Chairmen of

    The Regional and University Hospital Centres.

    AFM-Téléthon is an association for patients and parents of patients committed to fighting disease. Funds raised during the Telethon (€88.1 million in 2012) have enabled the association to become a major player in biomedical research on rare diseases in France and around the world. It currently supports clinical trials focusing on genetic disorders affecting the eyes, the blood, the brain, the immune system, the muscular system, etc. In addition, this association has the unique advantage of being able to develop, produce and test innovative therapeutic medicines via its laboratory, Généthon. Thanks to telethon donations, AFM-Téléthon has pledged nearly €7 million to clinical and pre-clinical work for this trial since 2003.

    Vaincre les Maladies Lysosomales (VML) is a state-approved charitable organization created by parents of sick children in 1990. It aims to find cures for patients suffering from lysosomal diseases. The organization has three main focus areas: supporting patients and their families, encouraging scientific and medical research and raising public awareness on the subject of rare diseases. Since 1992, VML has financed the fundamental and pre-clinical research for the gene therapy trial and since 2012 has helped finance the clinical trial.

    The Paris Public Hospital Network (AP-HP)

    AP-HP, which serves the Greater Paris area, is the number one teaching hospital in Europe. Its 92,000-strong staff is committed to giving round-the-clock, top quality healthcare to all patients. Each year 7 million people benefit from state-of-the-art treatments available in all fields of medicine.

  6. flosz 22 september 2015 11:45
    "Uit de losse pols"

    WC/CC Charles Richard 09:55.....
    @ 12:00
    .....mild painful sensory neuropathy in members of a large Canadian pedigree. Mutations here where found in one copy of the NAGLU gene/45% normal activity.....
    difficult to diagnose milder forms of SanfilippoB may actually form a large reservoir of undiscovered patients who could ultimately benefit from gene replacement therapy.
  7. flosz 22 september 2015 14:40
    uniQure’s First AMT-110 Gene Therapy Results Encouraging

    Over the weekend, the scientific and investing communities had a first look at 1-year follow-up results for AMT-110, uniQure’s (QURE) gene therapy candidate for the treatment of Sanfilippo B. Details are limited as uniQure negotiates the acquisition of this data from partner Institut Pasteur, but so far we’re encouraged by the results. A conference call Monday morning helped fill in some gaps, and our view is that uniQure has an intriguing drug candidate on its hands, certainly worth moving forward into larger studies.

    In afwachting van volledig art., plaatsing op twitter zal spoedig volgen imho.
  8. flosz 30 november 2015 16:07
    Sanfilippo B Program Update
    · Positive one-year follow-up results from four Sanfilippo B patients participating in a Phase 1/2 clinical trial were presented by Prof. Marc Tardieu representing Institut Pasteur, uniQure’s collaborator, at the ESGCT and FSGT Collaborative Congress on September 19, 2015. The trial demonstrated durable increases in NAGLU expression in the cerebrospinal fluid (CSF) of 14% to 17% at 12-months post treatment. It also showed that incremental cognitive development was maintained in all four patients with no evidence of progressive brain atrophy. The trial provided the first clinical validation of the Company’s proprietary AAV5 vector effectively delivering a target gene into the CNS leading to durable expression of NAGLU protein in the CNS.

    · Subsequently, Prof. Tardieu presented a post-hoc biochemical analysis of glycosaminoglycans (GAG) levels in the CSF using samples from the same four patients. The results were presented at the International Conference on Sanfilippo Syndrome and Related Lysosomal Storage Diseases in Geneva on November 27, 2015. A decrease of Heparan sulfate, a brain-predominant GAG and a substrate for the NaGlu enzyme, could not be detected in the CSF. This result resembles a previously published study by Ausseil and colleagues using uniQure’s AAV5 NAGLU gene therapy vector in a canine model of Sanfilippo B, where durable NAGLU expression in the dog brain resulted in significant reductions of brain tissue GAGs, although CSF GAGs were unchanged (previously unpublished). Given the encouraging positive clinical results previously reported, and the difficulty in interpreting CSF GAGs as a biomarker predictive of clinical benefit, uniQure is aggressively moving forward with its plans to complete the in-license of the data from the Company’s collaborator, prepare the future pathway with regulatory authorities and complete close follow-up of the patients through the end of the 30-month study, expected around year-end 2016.
  9. flosz 28 januari 2016 09:07
    Journée de la recherche translationnelle,Paris,April 6. Marc Tardieu, Gene therapy in Sanfilippo disease

    14th International Symposium on MPS and Related Diseases.Germany,14th – 17th July 2016. Speakers: Marc Tardieu.

    12th Annual WORLDSymposium lysosomal diseases
    February 29 – March 4, 2016 in San Diego!
  10. DrMedicalValue 3 maart 2016 11:55
    Groot discussiepunt wordt hier: is verlaging van 25% van Heparan Sulfaat (HS is het relevante glucosamine-glycan) in de liquor voldoende voor een klinisch effect? Bij QURE zie je geen verlaging van HS spiegels in de liquor en toch mogelijk een goed klinisch effect, zoals in studies bij honden ook is gezien..... Alexion zegt niet over klinische effecten of de relevantie van HS...
  11. flosz 4 april 2016 12:59
    Positive Results from Phase I/II Study of AMT-110 in Sanfilippo B -- On September 19, 2015, encouraging results from an academic-sponsored Phase I/II trial in Sanfilippo B using uniQure's novel AAV5-based gene therapy were presented at the European Society of Gene and Cell Therapy (ESGCT) in Helsinki, Finland. In all four patients, researchers verified the restoration of catalytical activity of the NaGlu protein in the cerebrospinal fluid (CSF) from 0% at baseline up to 14-17% of normal at three months and maintained further at 12 months. The trial also demonstrated that incremental cognitive development was maintained in all four patients with no progression of brain atrophy detected via MRI scans. These data validate the effective transmission of the NaGlu gene into the brain with uniQure's proprietary AAV5 viral vector. uniQure expects to present 30-month follow-up data from the four patients in early 2017.

    Sponsorship of Extension Protocol for Phase I/II Study of AMT-110 to Transition to uniQure -- In January 2016, uniQure and the academic consortium comprised of Institut Pasteur, the French Muscular Dystrophy Association, Vaincre les Maladies Lysosomales and Institut National de la Sante et de la Recherche Medicale (INSERM), executed a term sheet reflecting the license of certain data and intellectual property from the consortium-sponsored Phase I/II study of AMT-110 in Sanfilippo B. uniQure and the consortium are currently negotiating the terms of a definitive agreement. Additionally, uniQure has assumed the sponsorship of the Phase I/II extension study, enabling the Company to continue the follow-up of the four patients treated to date.
  12. flosz 6 april 2016 17:43

    flosz schreef op 28 januari 2016 09:07:

    Journée de la recherche translationnelle,Paris,April 6. Marc Tardieu, Gene therapy in Sanfilippo disease : Marc Tardieu from @HUParisSud present jaw-dropping intra-cerebral gene therapy at #JRT2016
  13. flosz 17 februari 2017 00:21
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