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ontwikkelingen Parkinson / Parkinson's disease

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[verwijderd] 5 augustus 2013 09:49

dit draadje gestart t.b.v. alle highlights op Parkinson's disease

in de bijlage het PDFje (NL).

in het Engels:

uniQure announces start of Parkinson’s disease gene therapy Phase I trial by UCSF/NIH to test its GDNF gene in patients

Jul 29, 2013

uniQure announces start of Parkinson’s disease gene therapy Phase I trial by UCSF/NIH to test its GDNF gene in patients

Appointment of Professor Krystof Bankiewicz, UCSF, as chair of uniQure’s CNS Scientific Advisory Board
Amsterdam, the Netherlands, July 29, 2013 — uniQure B.V., a leader in human gene therapy, today announced the start of a human trial in Parkinson’s disease with glial cell line-derived neurotrophic factor (GDNF). The gene therapy developed by researchers at the University of California, San Francisco (UCSF), uses the GDNF gene, which uniQure licensed from Amgen. This trial is part of a wide-ranging collaboration between uniQure and UCSF and represents one of uniQure’s suite of GDNF-based gene therapies in development targeting disorders of the central nervous system.

uniQure and UCSF’s joint program is an investigator initiated clinical trial in Parkinson’s disease, led by Dr. Krystof Bankiewicz MD, PhD, at UCSF, and Dr. John D. Heiss, MD, at the National Institute for Neurological Disorders and Stroke, part of the National Institutes of Health (NIH). Using the ClearPoint Neuro Interventional System, Dr. Bankiewicz’s team administered the GDNF gene packaged in an AAV vector to the brain of a first Parkinson’s patient. The ClearPoint system has been developed to allow real-time observation of brain surgery, allowing unmatched precision of gene therapy delivery. The hypothesis is that GDNF’s neuro-regenerative and protective properties may protect and strengthen brain cells that produce dopamine. Dopamine is a chemical that affects brain function. People with Parkinson's disease have problems producing dopamine in a specific area in the brain responsible for the control of body movements. The study is a Phase I open-label dose escalation safety study that will include 24 patients divided over 4 cohorts. The first patient was dosed on May 20, and so far there have been no safety issues. The study is fully funded by the NIH.

“The start of this trial is the culmination of over 10 years of preclinical work performed at UCSF,” says Dr. Krys Bankiewicz of UCSF. “We are extremely proud to have optimized the delivery technologies together with our partners so that we can now safely deliver a gene therapy product into a minuscule space in the brain, including the putamen, observe the surgery in real-time and guarantee the highest possible level of quality and precision of gene delivery. uniQure is our partner of choice for the development of the therapy as they are first in having mastered the vector design, as well as the development and manufacturing challenges gene therapy developers faced in the past.”

Under the terms of the collaboration, uniQure will have the rights to the results of the study as well as the IND. In exchange uniQure will manufacture the GDNF-AAV construct using its baculovirus platform for the next phases of the study.

In addition, uniQure is collaborating on a range of GDNF-based CNS disorders, such as multiple system atrophy (MSA), Huntington’s disease, and hearing loss together with Université de Toulouse (France), University of Cambridge (UK), and UCSF. Using AAV5, which has a strong tropism for the CNS, the partners will evaluate these programs up to preclinical proof of concept. As part of this work, uniQure and UCSF are currently developing administration of AAV5 to the cerebrospinal fluid to facilitate broad distribution of substance in the brain.

uniQure has appointed Dr. Bankiewicz chair of its CNS Scientific Advisory Board. Dr. Bankiewicz is the Kinetics Foundation Chair in Translational Research and Professor in Residence of Neurological Surgery and Neurology at UCSF. His research focus is restorative interventions, specifically drug delivery and gene transfer, in models of Parkinson's disease and brain tumors. His laboratory studies delivery of therapeutic agents into the central nervous system through cell-implantation, convection-enhanced and gene transfer-based delivery methods, as well as in vivo applications of MRI and PET to detect in-vivo changes in the brain and their correlation with functional outcome.

“Success in CNS gene therapy is to a large extent dependent on cutting edge delivery technologies. Capitalizing on the unique and broad collaboration with UCSF, in particular the outstanding group in Dr. Bankiewicz’ laboratory, we are accessing and developing leading CNS gene delivery technologies. This Parkinson trial also demonstrates the potential of the Company’s gene therapy techologies to reach beyond orphan diseases. The modular approach of our manufacturing platform and the use of AAV5 will allow us to rapidly advance a portfolio of promising programs targeting CNS disorders,” said Jörn Aldag, CEO of uniQure.

Bijlage:

bilbo3 13 augustus 2013 12:07

1e patient is behandeld:

MRI Interventions' ClearPoint System Enables Precise Delivery ofPromising Investigational Gene Therapy in Parkinson's Disease Phase IClinical Trial

First Patient Treated in Phase I Safety Study Led by Researchers at University of California, San Francisco (UCSF) and National Institutes of Health (NIH) and Utilizing uniQure's GDNF Gene

IRVINE, CA, Aug 12, 2013 (Menafn - Marketwired via COMTEX) --MRI Interventions, Inc. (otcqb:MRIC) today announced treatment ofthe first patient in a Phase I clinical trial utilizing uniQureB.V.'s glial cell line-derived neurotrophic factor (GDNF) fortreatment of Parkinson's disease. This gene therapy holds promise inthe battle against the degenerative and debilitating disorder, whichaffects 1.5 million people in the United States. MRI Interventions'ClearPoint Neuro Intervention System is being used in the clinicaltrial to enable direct infusion of the gene therapy into an area ofthe brain affected by Parkinson's disease.

www.menafn.com/9d5cfc4e-c829-4950-84f...

flosz 20 november 2013 07:27

Real Time MRI Guidance and Visualization for Brain Surgery Using Clearpoint System: Interview with CEO of MRI Interventions
www.medgadget.com/2013/11/real-time-m...
www.youtube.com/watch?v=i5uavLiplP8&a...

flosz 3 februari 2017 12:42

Draadje PD uit de krochten....

Parkinson's UK/MedGenesis:

GDNF: A future treatment for Parkinson's? Part 1 of 2
m.youtube.com/watch?v=XcZQEct4yCI

GDNF: A future treatment for Parkinson's? Part 2 of 2 Parkinson's
m.youtube.com/watch?v=kE6-b9DY3mI

Stukje geschiedenis erbij:
June 2012, uniQure signed an agreement to partner with UCSF and the NIH on GDNF gene therapy for Parkinson’s.
In July 2013, Dr Krystof Bankiewicz, UCSF, was appointed chair of uniQure’s CNS Scientific Advisory Board.
The gene therapy developed by researchers at the University of California, San Francisco (UCSF), uses the GDNF gene, which uniQure (formerly Amsterdam Molecular Therapeutics) licensed from Amgen.
So the GDNF gene is now housed in uniQure. It seems like a good home. Hopefully, data and access to GDNF will be made available to other researchers. This is almost a model collaboration between an academic research center, a biotech and the NIH to cure Parkinson’s. All that is missing now is the voice of the patient.
Another surprise was the out licensing of Amgen’s GDNF protein to MedGenesis, a biotech in Canada. In January 2010, Medgenesis announced “that it has successfully entered into an agreement with Amgen granting MedGenesis an exclusive, worldwide license for glial cell line-derived neurotrophic factor (GDNF) protein in CNS and non-CNS indications…” subject to the rights of a co-exclusive licensee for CNS indications in certain countries…“As part of the license agreement, Amgen now holds a small equity stake in MedGenesis…”

///////
QURE PD
Gene Therapy for Parkinson’s Disease: AAV5-Mediated Delivery of Glial Cell Line-Derived Neurotrophic Factor (GDNF)
link.springer.com/protocol/10.1007/97...

Regarding the academic-sponsored trial in Parkinson’s disease, uniQure will evaluate partnership opportunities to accelerate completion of the ongoing study and further develop the program.
hugin.info/157414/R/2056691/770399.pdf

flosz 3 februari 2017 13:51

+ uit de Pubmed-draad:

Perspective on the Road toward Gene Therapy for Parkinson's Disease www.ncbi.nlm.nih.gov/pmc/articles/PMC...

flosz 6 maart 2019 18:09

An investigator-led trial of $QURE ‘s gene therapy for #ParkinsonsDisease, AAV2-GDNF, aims to revive development, as protocol amendments are being discussed internally, said lead investigator Dr John Heiss twitter.com/biopharminsight/status/11...

Vitavita 6 maart 2019 18:30

Flosz, zeer interessant !!

Hieronder nog even de uitgeschreven tekst:

UniQure’s Parkinson’s gene therapy has investigators discussing protocol amendments to revive development; data from original Phase I submitted to journal, investigator says

By: Shuan Sim in New York
27 Feb 2019

An investigator-led trial of UniQure’s (NASDAQ:QURE) gene therapy for Parkinson’s disease, AAV2-GDNF, aims to revive development, as protocol amendments are being discussed internally, said lead investigator Dr John Heiss, chair of the surgical neurology branch, National Institute of Neurological Disorders and Stroke (NINDS). The glial cell line-derived neurotrophic factor (GDNF) gene therapy is being developed by the University of California, San Francisco (UCSF), while the trial is sponsored by NINDS, and an upcoming trial initiation—timeline still to be established—will have an amended protocol from an active Phase I trial, he said.

This development is being closely watched, experts noted, as little data is available and the gene therapy is being developed as a neuroprotective treatment, thus addressing Parkinson’s beyond symptomatic gene therapies from Voyager Therapeutics (NASDAQ:VYGR) and Axovant (NASDAQ:AXGT). Analysts see AAV2-GDNF as a close competitor to Voyager's VY-AADC (AAV2 1-amino acid decarboxylase; AADC) and Axovant’s Axo-Lenti-PD (AADC, tyrosine hydroxylase and CH1 lentiviral), projecting sales of USD 850m in 2029 and USD 1bn in 2025 for the Voyager and Axovant assets, respectively.

flosz 3 april 2019 13:34

Even plakken...

twitter.com/ridemytrike/status/111338...
PD,12:52 www.iex.nl/Forum/Topic/1286603/336/Wa...

Phase 1 Trial of Convection-Enhanced Delivery of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor in Patients with Advanced Parkinson’s Disease

Authors: Davis Palmer Argersinger, B.S.; Codrin Lungu, MD; Dima Hammoud, MD; Peter Herscovitch, MD; Debra Ehrlich, MD; Gretchen Scott; Krystof Bankiewicz, MD, PhD; Kareem Zaghloul, MD, PhD; Mark Hallett, MD; Russell Lonser, MD; John Heiss, MD (Washington, DC)

Introduction:
Parkinson’s disease is progressive and presently incurable. GDNF is a neurotrophic factor that prevented the death of dopaminergic neurons in culture and animal models of Parkinson’s disease (PD).

Methods:
In this Phase 1 clinical trial, 13 adult patients with advanced PD underwent convection-enhanced delivery (CED) of an adeno-associated virus, serotype 2 vector containing glial cell line-derived neurotrophic factor (AAV2-GDNF) to investigate the safety, tolerability, and potential clinical effects of CED of AAV2-GDNF and gadoteridol, a surrogate magnetic resonance imaging (MRI) tracer, into the bilateral putamina (450 µl per hemisphere). Three escalating dose levels were evaluated: 1) 9 x 1010vg (6 patients); 2) 3 x 1011vg (6 patients); and 3) 9 x 1011vg (1 patient). Intraoperative MRI was performed during infusions. Pre-operatively, and at 6-12 month intervals post-operatively, Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 assessed motor function and positron emission tomography (PET) scanning with [18F]DOPA assessed F-DOPA uptake, a sign of presynaptic dopaminergic integrity.

Results:
The patients tolerated AAV2-GDNF infusion without short- or long-term clinical or radiographic toxicity. MRI tracked AAV2-GDNF infusion within the bilateral putamina. Average coverage of the putamina was 22%. UPDRS Part 3 assessment scores remained stable throughout the study. Increased [18F]DOPA uptake in the infused areas was seen bilaterally in 10/13 patients at 6 months (range: 5-274%, median: 36%), and in 12/13 patients at 18 months after infusion (range: 8-130%, median: 54%).

Conclusion:
Patients with advanced PD tolerated bilateral CED of AAV2-GDNF without toxicity. Gadoteridol in the infusion solution tracked putaminal AAV2-GDNF distribution. PET findings of increased putaminal [18F]DOPA uptake suggest a neurotrophic effect on dopaminergic neurons. Based on a satisfactory safety profile, a follow-up clinical trial is planned to increase putaminal coverage and possibly reverse PD progression and signs.

flosz 3 april 2019 14:01

BBC docu PD & GDNF (Heftig!)

Bristol trial

The Parkinson's Drug Trial: A Miracle Cure?

Filmed over six years, The Parkinson’s Drug Trial: A Miracle Cure? follows a group of volunteers with Parkinson’s as they take part in a groundbreaking medical trial testing a drug called GDNF.
Forty-two patients undergo complex brain surgery and months of infusions via a port embedded into the side of their skull. Can this clinical trial give hope to the estimated 10 million affected by Parkinson’s globally?
In 2012, doctors from Frenchay and Southmead Hospitals in Bristol recruited volunteers to participate in a £3m trial, ending in 2017, to tackle the world’s second most common neurodegenerative condition. Forty-two volunteers living with Parkinson’s put their trust in neurosurgeon Professor Steven Gill, and the trial’s principle investigator neurologist Doctor Alan Whone, along with their team of medical experts.
“I’m giving you my body and I want you to find a cure,” says 57 year-old Kay Cotton from Cornwall, who’s had Parkinson’s for 10 years.
Other volunteers living with Parkinson’s include Bryn Williams, 42, from Glasgow who says it’s the chance to be “part of a trial that could truly shift medicine”, whilst Ron Johnson, 72, from Oxfordshire, simply wants “to be able to play football with my grandchildren”.
The drug being tested is GDNF - glial-cell derived neurotrophic factor. It’s a naturally occurring protein found in our brains, first linked to treating Parkinson’s in 1993.??It was discovered in the lab that, at a high dosage, GDNF had a restorative effect on dopamine neurons. Dopamine neurons are the cells affected in Parkinson’s that lead to slowness, rigidity and tremors among other symptoms.
In this moving first episode, Professor Gill performs surgery on all of the volunteers to implant the device he’s designed that enables delivery of GDNF to a deep part of the brain.
The surgery and infusions that follow are medical firsts, offering a new way of delivering drugs to the brain. It leads to Pfizer the world’s biggest pharmaceutical company, investing in GDNF and the Bristol delivery system part-way through the medical trial.
Forty-four year-old Tom Isaacs from?Hertfordshire?is one of the trial’s most severely-affected volunteers. Tom, who was diagnosed with Parkinson’s when he was 27, says that the diagnosis "stays with you every single second of every single day."

twitter.com/bbctwo/status/11058462249...
www.bbc.co.uk/programmes/m0002tjw

Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease academic.oup.com/brain/article/142/3/...

www.cureparkinsons.org.uk/gdnf-the-facts

flosz 2 mei 2019 00:10

quote:
flosz schreef op 3 april 2019 14:01:
BBC docu PD & GDNF (Heftig!)

Bristol trial

The Parkinson's Drug Trial: A Miracle Cure?

Filmed over six years, The Parkinson’s Drug Trial: A Miracle Cure? follows a group of volunteers with Parkinson’s as they take part in a groundbreaking medical trial testing a drug called GDNF.

Op zoek naar een parkinsonmedicijn, de BBC-docu voorzien van NL commentaar en ondertiteling.
www.npostart.nl/op-zoek-naar-een-park...

In deel 2, ong. 15 min. v.eind. vermelding dat MedGenesis GDNF octrooihouder is.

MedGenesis own the rights to GDNF medium.com/parkinsons-uk/meet-the-tea...

Vitavita 2 mei 2019 08:43

Parkinson’s gene therapy development to restart in summer 2019

By GlobalData Healthcare, 19 April 2019

Development of the Parkinson’s disease gene therapy that UniQure was previously involved in will be restarted in a Phase II trial this summer with the help of a private-public entity, said lead researcher Dr Krystof Bankiewicz, professor of neurological surgery, University of California, San Francisco (UCSF). The entity, to be called Brain Neu Bio, is a joint effort between UCSF and Ohio State University (OSU), and OSU will lead development.

Bankiewicz is moving to OSU in mid-April, after which Brain Neu Bio will be created. FDA discussions about the trial are ongoing, Bankiewicz noted, declining to disclose recruitment targets for the glial cell line-derived neurotrophic factor (GDNF) gene therapy. AAV2-GDNF represents the first gene therapy that could alter the progression of Parkinson’s disease, unlike dopamine-modulating gene therapies like those from Voyager Therapeutics and Axovant.

The Phase I trial had struggled to recruit and closed enrollment 12 patients short of its 25-patient target in February 2018, six years after opening, this news service reported on 27 February. Recruitment is expected to move along faster than the Phase I trial, Bankiewicz said. Phase II sites will include those that were in place for Phase I at UCSF and new sites at OSU, in the Midwest, and in Warsaw, Poland, where Bankiewicz has a medical centre. Sites from the National Institutes of Health (NIH) will not be used for the Phase II trial, but patients can be referred to the new sites, he said, as the NIH will not be involved.

OSU’s movement disorders clinic is larger and better equipped than what NIH had, said Bankiewicz, who will be the director of the OSU’s Center of Brain Heath and Performance and a professor of neurosurgery. Bankiewicz also expected his busy medical centre in Warsaw to help speed recruitment.

If recruitment goes well, some preliminary data could be expected in a year and a half from initiation, Bankiewicz said. Analysts see AAV2-GDNF as a competitor to Voyager’s VY-AADC and Axovant’s Axo-Lenti-PD. They project sales of $850m in 2029 and $1bn in 2025, respectively. The market caps for UniQure, Voyager and Axovant are $2.4bn, $623m and $219m, respectively.

UniQure inked a collaboration with UCSF in 2012, supplying the gene therapy product for the Phase I trial, which was funded by and co-developed with the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). While UniQure had previously obtained exclusive rights to Amgen’s patent on the gene, the UCSF agreement gave UniQure exclusive commercial rights to preclinical and Phase I data and an option to acquire the AAV2-GDNF program from UCSF should the Phase I show proof of concept, according to the 2012 press release.

The Amgen patent on the GDNF gene has expired and UniQure’s collaboration agreement with UCSF had been cancelled two years ago due to a lack of progress in the program, Bankiewicz said.

Since closing Phase I recruitment, UCSF and NINDS have worked on new protocols to revive development, as was previously reported. The Phase II trial will indeed adopt these protocol changes, noted Bankiewicz: enrolling moderate patients instead of moderate-to-severe, delivering along the posterior axis rather than the superior and increasing the vector volume. The vector volume is expected to triple, and it is hoped the changes will result in vector coverage that exceeds at least 50%, compared with Phase I’s 26% coverage via superior axis delivery, he said.

by Shuan Sim in New York

www.pharmaceutical-technology.com/com...

flosz 31 mei 2019 21:25

Trial of magnetic resonance-guided putaminal gene therapy for advanced #ParkinsonsDisease www.ncbi.nlm.nih.gov/pubmed/31145831
#GDNF AAV2-GDNF
twitter.com/floszcrxl/status/11345405...

Bijlage:

flosz 1 juli 2020 12:40

GDNF and Parkinson’s Disease: Where Next? A Summary from a Recent Workshop content.iospress.com/articles/journal...

AAV2-GDNF for Advanced #ParkinsonsDisease www.clinicaltrials.gov/ct2/show/NCT01...
(AAV2-GDNF= ex-QURE)

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