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PubMed UniQure

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flosz
0
Gene Ther. 2013 Oct 24. doi: 10.1038/gt.2013.58. [Epub ahead of print]
Therapeutic expression of hairpins targeting apolipoprotein B100 induces phenotypic and transcriptome changes in murine liver.
Abstract
Constitutive expression of short hairpin RNAs (shRNAs) may cause cellular toxicity in vivo and using microRNA (miRNA) scaffolds can circumvent this problem. Previously, we have shown that embedding small interfering RNA sequences targeting apolipoprotein B100 (ApoB) in shRNA (shApoB) or miRNA (miApoB) scaffolds resulted in differential processing and long-term efficacy in vivo. Here we show that adeno-associated virus (AAV)-shApoB- or AAV-miApoB-mediated ApoB knockdown induced differential liver morphology and transcriptome expression changes. Our analyses indicate that ApoB knockdown with both shApoB and miApoB resulted in alterations of genes involved in lipid metabolism. In addition, in AAV-shApoB-injected animals, genes involved in immune system activation or cell growth and death were affected, which was associated with increased hepatocyte proliferation. Subsequently, in AAV-miApoB-injected animals, changes of genes involved in oxidoreductase activity, oxidative phosphorylation and nucleic bases biosynthetic processes were observed. Our results demonstrate that long-term knockdown of ApoB in vivo by shApoB or miApoB induces several transcriptome changes in murine liver. The increased hepatocyte profileration by AAV-shRNA may have severe long-term effects indicating that AAV-mediated RNA interference therapy using artificial miRNA may be a safer approach for familial hypercholesterolemia therapy.Gene Therapy advance online publication, 24 October 2013; doi:10.1038/gt.2013.58.
PMID:24152580
www.ncbi.nlm.nih.gov/pubmed/24152580

J Gene Med. 2013 Jun-Jul;15(6-7):219-32. doi: 10.1002/jgm.2712.
Mir-142-3p target sequences reduce transgene-directed immunogenicity following intramuscular adeno-associated virus 1 vector-mediated gene delivery.
Abstract
BACKGROUND:
Muscle represents an important tissue target for adeno-associated virus (AAV) vector-mediated gene transfer in muscular, metabolic or blood-related genetic disorders. However, several studies have demonstrated the appearance of immune responses against the transgene product after intramuscular AAV vector delivery that resulted in a limited efficacy of the treatment. Use of microRNAs that are specifically expressed in antigen-presenting cells (APCs) is a promising approach for avoiding those immune responses. Cellular mir-142-3p, which is APC-specific, is able to repress the translation of its target cellular transcripts by binding to a specific target sequences.
METHODS:
In the present study, we explored the potential of mir-142-3p specific target sequences with respect to reducing or abolishing immune responses directed against ovalbumin (OVA), a highly immunogenic protein, expressed as transgene and delivered by AAV1 vector administered intramuscularly.
RESULTS:
The occurrence of immune responses against OVA transgene following intramuscular delivery by AAV have been described previously and resulted in the loss of OVA protein expression. In the present study, we demonstrate that OVA protein expression was maintained when mir-142-3pT sequences were incorporated into the expression cassette. The sustained expression of OVA protein over time correlated with a reduced increase in anti-OVA antibody levels. Furthermore, no cellular infiltrates were observed in the muscle tissue when AAV1 vectors containing four or eight repeats of mir-142-3p target sequences after the OVA sequence were used.
CONCLUSIONS:
The rising humoral and cellular immune responses against OVA protein after intramuscular delivery can be efficiently reduced by the use of mir-142-3p target sequences.
Copyright © 2013 John Wiley & Sons, Ltd.
KEYWORDS:
adeno-associated virus (AAV), gene therapy, immune responses, microRNA, mir-142-3p, transgene
PMID:23658149
www.ncbi.nlm.nih.gov/pubmed/23658149

Uit 2012:
Embedding siRNA sequences targeting Apolipoprotein B100 in shRNA and miRNA scaffolds results in differential processing and in vivo efficacy
www.ncbi.nlm.nih.gov/pmc/articles/PMC...

Murine CD4?CD25? cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo.
www.ncbi.nlm.nih.gov/pmc/articles/PMC...

Adeno-associated virus mediated delivery of Tregitope 167 ameliorates experimental colitis.
www.ncbi.nlm.nih.gov/pmc/articles/PMC...

Optimization and comparison of knockdown efficacy between polymerase II expressed shRNA and artificial miRNA targeting luciferase and Apolipoprotein B100.
www.ncbi.nlm.nih.gov/pmc/articles/PMC...
flosz
0
Glybera:

Regulatory evaluation of Glybera in Europe - two committees, one mission.
www.ncbi.nlm.nih.gov/pubmed/23954897
www.nature.com/nrd/journal/v12/n9/ful...
www.iex.nl/Forum/Topic/1290716/2/With...

History of gene therapy.
Abstract
Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.
www.ncbi.nlm.nih.gov/pubmed/23618815

Gene therapy on demand: site specific regulation of gene therapy.
Abstract
Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, ß-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients. Introduction of the therapeutic gene to the given cells should provide the level of expression which will restore the production of therapeutic protein to normal values or will provide therapeutic efficacy despite not fully physiological expression. However, in numerous diseases the expression of therapeutic genes has to be kept at certain level for some time, and then might be required to be switched off to be activated again when worsening of the symptoms may aggravate the risk of disease relapse. In such cases the promoters which are regulated by local conditions may be more required. In this article the special emphasis is to discuss the strategies of regulation of gene expression by endogenous stimuli. Particularly, the hypoxia- or miRNA-regulated vectors offer the possibilities of tight but, at the same time, condition-dependent and cell-specific expression. Such means have been already tested in certain pathophysiological conditions. This creates the chance for the translational approaches required for development of effective treatments of so far incurable diseases.
www.ncbi.nlm.nih.gov/pubmed/23566848

Lessons learned from the clinical development and market authorization of Glybera.
www.ncbi.nlm.nih.gov/pubmed/23808604
www.pharmachronicle.in/wp-content/upl...

Endgame: glybera finally recommended for approval as the first gene therapy drug in the European union.
www.ncbi.nlm.nih.gov/pmc/articles/PMC...
www.nature.com/mt/journal/v20/n10/pdf...
www.iex.nl/Forum/Topic/1286507/Last/M...

WATCH: The Story Behind Glybera Approval
www.genengnews.com/video-channel/insi...

Glybera and the future of gene therapy in the European Union.
www.ncbi.nlm.nih.gov/pubmed/22679644

Alipogene tiparvovec, an adeno-associated virus encoding the Ser(447)X variant of the human lipoprotein lipase gene for the treatment of patients with lipoprotein lipase deficiency.
Abstract
Amsterdam Molecular Therapeutics BV is developing alipogene tiparvovec (Glybera, AMT-011, AAV1-LPLS447X), a Ser(447)X variant of the human lipoprotein lipase (LPL) gene (LPLSer(447)X) in an adeno-associated virus vector, as a potential intramuscular gene therapy for the treatment of LPL deficiency. Familial LPL deficiency is a rare, autosomal-recessive disorder of lipoprotein metabolism that is characterized by severe hypertriglyceridemia with episodes of abdominal pain, acute pancreatitis and eruptive cutaneous xanthomatosis. The lack of functional LPL in patients with LPL deficiency causes an accumulation of triglyceride (TG)-rich lipoproteins in the plasma. The LPLSer(447)X variant is associated with decreased levels of plasma TGs and increased HDL cholesterol concentrations compared with wild-type LPL. Preclinical studies evaluating alipogene tiparvovec in a mouse model of LPL deficiency demonstrated a long-term, dose-dependent correction of the lipid abnormalities. The first clinical trials in patients with LPL deficiency appear promising, with a significant decrease in the levels of plasma TGs observed in the first 3 months following the administration of alipogene tiparvovec, and an increase in local LPL activity and protein levels observed after 6 months. In addition, a decrease in pancreatitis frequency was observed during a 3-year follow-up period. At the time of publication, a phase II/III trial in patients with LPL deficiency, being conducted to further support the submission of an MAA to the EMEA for alipogene tiparvovec, was ongoing. The compound is also under investigation for the treatment of type V hyperlipoproteinemia, Syndrome X and non-alcoholic steatohepatitis.
www.ncbi.nlm.nih.gov/pubmed/20072945
[verwijderd]
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poeh, mijn google-vertaler slaat op hol van deze wetenschappelijke publicaties...en mocht google dit ooit wel vertaald krijgen en daarbij ook nog uitleg geven, dan koop ik aandelen Google! ;-)

M.a.w., soms stijgen teksten boven mijn pet...mocht iemand de kern kunnen samenvatten in Jip&Janneke-taal, dan houd ik mij aanbevolen.

mvg ivet
stefano 1
0
Goede avond is iemand hier bij de vergadering geweest van vanmiddag zo ja is er nog iets bijzonders gezegt ??
Prof. Dollar
0
quote:

stefano 1 schreef op 18 november 2013 18:36:

Goede avond is iemand hier bij de vergadering geweest van vanmiddag zo ja is er nog iets bijzonders gezegt ??
Veelal duiding van bestaande feiten. De notulen volgen nog.

Verder is de afspraak gemaakt niet (meer) te speculeren (laat staan te citeren) op de IPO-waardering, zodat betrokken ongestoord hun werk kunnen doen.

Het lijkt mij in ieders belang om dat te respecteren. Verder is het vooral even geduld hebben.
[verwijderd]
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quote:

flosz schreef op 18 november 2013 09:49:

The compound is also under investigation for the treatment of type V hyperlipoproteinemia, Syndrome X and non-alcoholic steatohepatitis.
www.ncbi.nlm.nih.gov/pubmed/20072945

Zeg Flosz, dit is heel goed zoekwerk :)

Deze laatste 3 regeltjes zijn zeer veel belovend. Ze willen namelijk zeggen dat er nog meer ziekten zijn, waar Glybera tegen zou kunnen werken, anders stond het hier niet vermeld. Dat wil dus zeggen dat het niet bij de paar duizend patienten met LPLD blijft (mogelijk). Wanneer een therapie voor een ander probleem ook blijkt te werken kun je met zg 'off- label use' de hele goedkeuringsprocedure omzeilen. Goed nieuws dus:)

Groeten,

Frank
[verwijderd]
0
quote:

Prof. Dollar schreef op 18 november 2013 19:05:

[...]
Veelal duiding van bestaande feiten. De notulen volgen nog.

Verder is de afspraak gemaakt niet (meer) te speculeren (laat staan te citeren) op de IPO-waardering, zodat betrokken ongestoord hun werk kunnen doen.

Het lijkt mij in ieders belang om dat te respecteren. Verder is het vooral even geduld hebben.
Ik had niet de indruk dat betrokkenen zich ook maar iets aantrokken van onze speculaties, maar we hebben kennelijk toch meer invloed dan we denken :)

Groeten,

Frank
flosz
0
Hum Gene Ther. 2013 Dec 3.
Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPLS447X) in a phase II clinical trial of Lipoprotein Lipase deficiency (LPLD) gene therapy.
Abstract
Cellular immune responses to adeno-associated viral (AAV) vectors used for gene therapy have been linked to attenuated transgene expression and loss of efficacy. The impact of such cellular immune responses on the clinical efficacy of alipogene tiparvovec (Glybera®, AAV1-LPLS447X, uniQure, Amsterdam, the Netherlands), a gene-therapy consisting of intramuscular administration of a recombinant (r)AAV1 mediating muscle-directed expression of lipoprotein lipase (LPL), was investigated. Five subjects with LPL-deficiency (LPLD) were administered intramuscularly with a dose of 1 x 1012 gc/kg alipogene tiparvovec. All subjects were treated with immune suppression starting shortly before administration of alipogene tiparvovec and maintained until 12 weeks after administration. Systemic antibody and T cell responses against AAV1 and LPLS447X, as well as local cellular immune responses in the injected muscle were investigated in 5 LPLD subjects. Long term transgene expression was demonstrated despite a transient systemic cellular response and a stable humoral immune response against AAV1 capsid protein. Cellular infiltrates were found in 4 of the 5 subjects but were not associated with adverse clinical events or elevation of inflammation markers. Consistent herewith, CD8-positive T cells in the infiltrates lacked cytotoxic potential. Furthermore, FoxP3-positive/CD4-positive T cells were found in the infiltrates suggesting that multiple mechanisms contribute to local tolerance. Systemic and local immune responses induced by intramuscular injection of alipogene tiparvovec have no impact on safety and did not compromise LPL transgene expression. These findings support the use of alipogene tiparvovec in individuals with LPLD and indicate that muscle directed AAV-based gene therapy remains a promising approach for the treatment of human diseases.
www.ncbi.nlm.nih.gov/pubmed/24299335
bilbo3
0
Hieronder een uitgebreide samenvatting van de trials van glybera, ik heb er doorheen gekeken,maar voor mij te technisch. wellicht dat anderen er wel iets uit kunnen concluderen. zo ja ben ik erg benieuwd naar hun reactie.

online.liebertpub.com/doi/pdfplus/10....
flosz
0
AAV Empty Capsids: For Better or for Worse?

Encapsidated baculovirus DNA was one of six major product quality concerns identified during licensure assessment of Glybera;6 it was noted therein that the sequences adjacent to the expression cassette were preferentially packaged, consistent with reverse packaging from the ITRs. A key concern was whether open reading frames in these DNA impurities could be expressed and thereby contribute to immunotoxicity.
……
www.nature.com/mt/journal/v22/n1/pdf/...

Synthetic biology in mammalian cells: next generation research tools and therapeutics
www.nature.com/nrm/journal/vaop/ncurr...

Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies
www.nature.com/gt/journal/vaop/ncurre...

Birth of a New Therapeutic Platform: 47 Years of Adeno-associated Virus Biology From Virus Discovery to Licensed Gene Therapy
www.nature.com/mt/journal/v21/n11/ful...
Prof. Dollar
0
quote:

flosz schreef op 17 maart 2014 09:23:

Immune Responses to AAV-Vectors, the Glybera Example from Bench to Bedside
journal.frontiersin.org/Journal/68071...

Dank! Het belangrijkste:
"These findings show that muscle-directed AAV-based gene therapy remains a promising approach for the treatment of human diseases."

Misschien dat uniQure deze sectie weer eens moet bijwerken?
www.uniqure.com/news/scientific-publi...
[verwijderd]
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uniQure and Chiesi Announce Six Year Follow-up Data from Glybera® Treated Patients

Mar 17, 2014

uniQure N.V. today announced initial analysis of retrospectively collected individual patient data from LPLD patients treated with Glybera®.


Amsterdam, the Netherlands, and Parma, Italy, March 17, 2014 — uniQure N.V. (Nasdaq: QURE), a leader in human gene therapy, and Chiesi Farmaceutici S.p.A. (“Chiesi”), a leading international pharmaceutical company, today announced initial analysis of retrospectively collected individual patient data from LPLD patients treated with Glybera®. The analysis covers follow-up data for up to six years post treatment for 13 patients, all of whom met indication requirements for the current labeling of Glybera in the EU. This analysis represents an extension of the case note review which formed a part of the data package upon which the European Commission approved Glybera in October 2012 under exceptional circumstances for the treatment of a subset of patients with lipoprotein lipase deficiency, or LPLD, a potentially life-threatening, orphan metabolic disease. Glybera currently is not approved for use outside of the European Union.

An external adjudication board of independent experts performed the review of the individual patient profiles. In the analysis equal time periods of up to six years before and after Glybera treatment were compared to evaluate the number and severity of attacks of pancreatitis in each LPLD patient with a history of severe or repeated pancreatitis. The review suggests that treatment with Glybera provides long-term beneficial effects with regard to the risk of encountering new pancreatitis events, including the occurrence of severe pancreatitis events. These results are in line with the trend exhibited in the first case note review performed up to 3 years after treatment with Glybera.

"Despite the small number of patients in the study, it is encouraging to note that this new single treatment paradigm continues to indicate long term and relevant clinical benefit in a patient population that has no other treatment option," said Daniel Gaudet, MD, Ph.D., Associate Professor of Medicine, Université de Montreal, who was the leading investigator during the majority of the clinical studies performed with Glybera.

John Kastelein, MD, Ph.D., Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam, who was among the inventors of Glybera, highlighted how the trend of long term benefit combined with a very encouraging safety profile of Glybera differentiates the gene therapy approach: "I hope that this approach of treating patients with severe lipid disorders will lead to additional gene therapy initiatives in our field."

Glybera is indicated for the treatment of adult patients diagnosed with familial LPLD confirmed by genetic testing and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. LPLD results in hyperchylomicronemia, or dramatic and potentially life-threatening increases in the level of large fat-carrying particles, called chylomicrons, in the blood after eating. In many cases, LPLD and the associated elevated levels of chylomicrons can cause acute and potentially life-threatening inflammation of the pancreas, known as pancreatitis, thus leading to frequent hospitalizations. Recurrent pancreatitis can lead to chronic abdominal pain, pancreatic insufficiency - which is an inability to properly digest food due to a lack of digestive enzymes made by the pancreas -, and diabetes. There is no other approved treatment for LPLD.


Hunter300
0
Toch gek, je zou toch denken dat dit goed nieuws is....... En waarom is dit forum stilgevallen. Er werd toch alleen maar gevraagd voor de IPO niet te veel over de prijs te speculeren. Is er een ander forum? Of een emailgroep n.a.v. de bijeenkomst?
flosz
0
Drugs. 2015 Feb;75(2):175-82. doi: 10.1007/s40265-014-0339-9.

Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency.

Alipogene tiparvovec (Glybera(®); AMT-011, AAV1-LPL(S447X)) is an adeno-associated virus serotype 1-based gene therapy for adult patients with familial lipoprotein lipase (LPL) deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It is administered as a one-time series of intramuscular injections in the legs. LPLD, a rare autosomal recessive disorder, results in hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, the most debilitating of which is recurrent severe and potentially life-threatening pancreatitis. In clinical studies (n = 27 patients), one-time administration of alipogene tiparvovec was associated with significant reductions in plasma triglyceride levels during the 12 or 14 week study period post administration. Although triglyceride levels returned to pre-treatment levels within 16-26 weeks after administration, patients had sustained improvements in postprandial chylomicron metabolism, with sustained expression of functional copies of the LPL (S477X) gene and of biologically active LPL in skeletal muscle. Moreover, after up to 6 years' follow-up post administration, there were clinically relevant reductions in the incidence of documented pancreatitis and acute abdominal pain events consistent with pancreatitis. Alipogene tiparvovec was generally well tolerated, with most adverse events being localized, transient, mild to moderate injection-site reactions. This article reviews the pharmacology of alipogene tiparvovec and its efficacy and safety in adults with LPLD.
www.ncbi.nlm.nih.gov/pubmed/25559420

State-Of-The-Art Human Gene Therapy: Part I. Gene Delivery Technologies
Published on July 25, 2014
www.discoverymedicine.com/Dan-Wang/20...
flosz
0
Re-examination of regulatory opinions in Europe: possible contribution for the approval of the first gene therapy product Glybera

The first commercially approved human gene therapy in the Western world is Glybera (alipogene tiparvovec), which is an adenoassociated viral vector encoding the lipoprotein lipase gene. Glybera was recommended for marketing authorization by the European Medicines Agency in 2012. The European Medicines Agency had only ever reviewed three marketing authorization appli- cations for gene therapy medicinal products. Unlike in the case of Glybera, the applications of the first two products, Cerepro and Contusugene Ladenovec Gendux/Advexin, both of which were for cancer diseases, were withdrawn. In this report, we studied the European public assessment reports of the three gene therapy products. During the assessment process, Glybera was re-examined and reviewed for a fourth time. We therefore researched the re-examination procedure of the European Union regulatory process. Approximately 25% of the new medicinal products initially given negative opinions from the Committee for Medicinal Products for Human Use were ultimately approved after re-examination from 2009 to 2013. The indications of most medicines were changed during the re-examination procedure, and the products were later approved with a mode of approval. These results suggested that the re-examination system in the European Union contributed to the approval of both several new drugs and the first gene therapy product.
Molecular Therapy — Methods & Clinical Development (2015) 2, 14066; doi:10.1038/mtm.2014.66; published online 11 February 2015

www.nature.com/articles/mtm201466.pdf
[verwijderd]
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uit de NRC van donderdag:

Experimenteel onderzoek: Onderzoekers in de VS zijn er in geslaagd het hiv-virus bij apen onklaar te maken met eiwit. Critici zijn nog sceptisch.

Amsterdam. Een nieuwe gentherapie beschermt apen beter tegen hiv dan een vaccinatie met de best werkende antilichamen die ooit tegen hiv zijn ontwikkeld. Vier makaken die deze experimentele behandeling kregen, raakten geen van alle geïnfecteerd, terwijl zij in de 40 weken na de beschermende injectie tot vier keer toe met toenemende doses hiv direct in de bloedbaan werden ingespoten. Een Amerikaanse onderzoeksgroep onder leiding van Mike Farzan van The Scripps Research Laboratory in Jupiter, Florida, publiceerde deze resultaten gisteren in tijdschrift Nature.

Er zijn dus ook nog andere gebieden voor gentherapie.
flosz
0
Via: mobile.twitter.com/srqstockpicker

Gene Therapy Improves Clinical Outcomes in Patients With Lipoprotein Lipase Deficiency: Presented at EAS

By Jenny Powers

GLASGOW, Scotland -- March 27, 2015 -- Alipogene tiparvovic gene therapy improves clinical outcomes in patients with lipoprotein lipase deficiency (LPLD), researchers reported here at the 83rd European Atherosclerosis Society (EAS) Congress.

A gene therapy treatment approach in LPLD resulted in sustained expression of the transgene protein and improved chylomicron clearance.

In addition, disease-related clinical events decreased by 40% to 60% and hospitalisation/ICU days due to documented pancreatitis were reduced by 48% after therapy.

“The current treatment for patients with LPLD is a diet that allows less than 20 grams of fat per day -- a diet that is very difficult to adhere to,” noted Sophie Bernelot-Moens, Academic Medical Center, Amsterdam, the Netherlands.

A total of 27 subjects received 3 different dosages of a LPL gain-of-function gene cassette packaged into an AAV1 vector via intramuscular administration to the leg musculature.

Prior to therapy, nearly all patients in the study had already had at least 1 episode of acute pancreatitis. Within a 6-year follow-up, acute abdominal pain events consistent with pancreatitis decreased by 39%.

Similarly, post-prandial clearance of chylomicrons significantly improved from baseline in 5 patients who were tested at weeks 14 and 52 post-treatment. At 9 hours after eating, chylomicron levels were 0.65% per 100 mL of plasma in untreated patients. Following therapy, the levels of chylomicrons was 0.1% in 3 patients and <0.05% in 2 patients at 14 weeks post therapy. These levels continued to decrease, and reached 0% in 2 patients at 52 weeks post therapy.

“Chylomicronemia places patients with LPLD at high risk for pancreatitis,” said Bernelot-Moens.

No emerging safety concerns were observed in any of the patients receiving gene therapy. The most commonly reported adverse event (AE) was local pain, stiffness, or burning in the muscle following injections. The most commonly reported serious AE was pancreatitis due to the underlying disease.

There were 2 deaths on study, which were determined to be unrelated to gene therapy.

No immune response against the LPL protein was recorded, and there was no signal of teratogenicity following gene therapy; 1 woman had 2 successful pregnancies, and the partner of a male subject also had 2 successful pregnancies.

[Presentation title: Gene Therapy for Lipoprotein Lipase Deficiency (LPLD): Final Results of 3 Prospective Gene Therapy Clinical Studies and 1 Retrospective Clinical Events Analysis. Abstract 234]
www.firstwordpharma.com/node/1272179#...
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