Tagged: gene therapy

Dream, struggle, create, Prevail

 

The recent documents filed with the U.S. Securities and Exchange Commission by the biotech firm Prevail Therapeutics provides interesting insight into the bold plans of this company which was only founded in 2017.

Even more recent news that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for its lead experimental treatment – PR001 – suggests that this company is not wasting any time. 

PR001 is a gene therapy approach targeting GBA-associated Parkinson’s.

In today’s post, we will discuss what GBA-associated Parkinson’s is, how Prevail plans to treat this condition, and discuss what we know about PR001.

 


Caterina Fake. Source: TwiT

The title of this post comes is from a quote by Caterina Fake (co-founder of Flickr and Hunch (now part of Ebay)), but it seemed appropriate.

This post is all about dreaming big (curing Parkinson’s), the struggle to get the research right, and to create a biotech company: Prevail Therapeutics.

What is Prevail Therapeutics?

Prevail is a gene therapy biotech firm that was founded in 2017.

The company was founded by Dr Asa Abeliovich:

Dr Asa Abeliovich. Source: Prevail

It was set up in a collaborative effort with The Silverstein Foundation for Parkinson’s with GBA (Click here to read a previous SoPD post about this organisation) and OrbiMed (a healthcare-dedicated investment firm).

What does Prevail Therapeutics do?

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When disco-needs-ya, can gene therapy help ya?

 

With the recent announcement that the STEADY-PD III/Isradipine clinical trial did not reach its primary end point (that of slowing the progression of Parkinson’s), the winds of change have shifted with calls for a focus on biomarkers and better treatments, rather than disease modification.

Recently, researchers at Michigan State University have reported a novel experimental gene thearpy method for dealing with one of the most debilitating aspects of Parkinson’s – dyskinesias.

Ironically, their approach involves the same calcium channels that Isradipine blocks.

In today’s post, we will look at what dyskinesias are, what gene therapy is, and how this new approach could be useful for people currently burdened by these involutary movements.

 


Dyskinesia. Source: JAMA Neurology

There is a normal course of events following a diagnosis of Parkinson’s.

Yes, I am grossly over-generalising.

And no, I’m not talking from personal experience (this is based on listening to a lot of people), but just go with me on this for the sake of discussion.

First comes the shock of the actual diagnosis. For many it is devastating news – an event that changes the course of their lives. For others, however, the words ‘you have Parkinson’s‘ can provide a strange sense of relief that their current situation has a name and gives them something to focus on.

This initial phase is usually followed by the roller coaster of various emotions (including disbelief, sadness, anger, denial). It depends on each individual.

The emotional rollercoaster. Source: Asklatisha

And then comes the period during which many will try to familiarise themselves with their new situation. They will read books, search online for information, join Facebook groups (Click here for a good one), etc.

That search for information often leads to awareness of some of the realities of the condition.

And one potential reality that causes concern for many people (especially for people with young/early onset Parkinson’s) is dyskinesias.

What are dyskinesias?

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The other GDNF clinical trial

 

Glial cell-line derived neurotrophic factor (or GDNF) has been a topic of heated discussion in the Parkinson’s community for a long time. Most recently due to the announcement of the results of the Phase II Bristol GDNF clinical trial results, which did not meet the primary end points of the study (Click here to read more about that).

This week at the annual American Association of Neurological Surgeons conference in San Diego, the results of another GDNF clinical trial were presented.

This new study was a Phase I study assessing the safety and tolerability of a gene therapy approach for GDNF in people with Parkinson’s.

In today’s post, we will discuss what gene therapy is, what the new trial results indicate, and what the researchers may be planning to do next for this new clinical trial programme.

 


Source: AANS

Every year members of the American Association of Neurological Surgeons gather together in one spot and compare data/research/clinical notes.

This year the 87th AANS Annual Scientific Meeting was held in spectacular San Diego.

San Diego. Source: AFP

From Saturday 13th April through till Wednesday 17th, clinicians and researchers attended lectures and discussed new data on every aspect of neurological surgery. While I did not (nor planned to) attend the meeting, I was very interested to learn more about one particular presentation.

It involved the announcement of the results of a clinical trial which was focused on a gene therapy approach for Parkinson’s.

The treatment involved GDNF (Click here to read the abstract).

What is GDNF?

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The Bristol GDNF results

 

Today – 27th February, 2019 – the long-awaited results of the Phase II GDNF clinical trial were published.

GDNF (or glial cell line-derived neurotrophic factor) is a protein that our bodies naturally produce to nurture and support cells. Extensive preclinical research suggested that this protein was particularly supportive of dopamine neurons – a group of cells in the brain that are affected by Parkinson’s.

The results of the Phase II clinical trial suggest that the treatment was having an effect in the brain (based on imaging data), but the clinic-based methods of assessment indicated no significant effect between the treatment and placebo groups.

In today’s post we will look at what GDNF is, review the previous research on the protein, discuss the results of the latest study, and look at what happens next.

And be warned this is going to be a long post!

 


Boulder, Colorado. Source: Rps

It all began way back in 1991.

George H. W. Bush was half way into his presidency, a rock band called Nirvana released their second album (‘Nevermind’), Michael Jordan and the Chicago Bulls rolled over the LA Lakers to win the NBA championship, and Arnold Schwarzenegger’s ‘Terminator 2’ was the top grossing movie of the year.

Source: Stmed

But in the city of Boulder (Colorado), a discovery was being made that would change Parkinson’s research forever.

In 1991, Dr Leu-Fen Lin and Dr Frank Collins – both research scientists at a small biotech company called Synergen, isolated a protein that they called glial cell-derived neurotrophic factor, or GDNF.

And in 1993, they shared their discovery with the world in this publication:

Title: GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.
Authors: Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F.
Journal: Science, 1993 May 21;260(5111):1130-2.
PMID: 8493557

For the uninitiated among you, when future historians write the full history of Parkinson’s, there will be no greater saga than GDNF.

In fact, in the full history of medicine, there are few experimental treatments that people get more excited, divided, impassioned and evangelical than GDNF.

This ‘wonder drug’ has been on a rollercoaster ride of a journey.

What exactly is GDNF?

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The good, the GAD, and the not-so ugly

 

This post is a game of two halves.

The first half will explain the concept of a surgical procedure for Parkinson’s called ‘subthalamic deep brain stimulation‘, in which doctors permenantly implant electrodes into the brain to stimulate a region – the subthalamic nucleus. By stimulating this region with electrical impulses, doctors can provide a better quality of life (in most cases) to people with severe features of Parkinson’s.

In the second half of this post, we will look at an approach to doing the same thing,… but without the electrodes.

Rather, researchers are using gene therapy.

In today’s post, we will discuss what deep brain stimulation is, what gene therapy is, and how the gene therapy approach is having a different kind of impact on the brain to that of deep brain stimulation.

 


maxresdefault

Source: Youtube

Welcome to the first half of today’s post.

It begins with you asking the question:

What is deep brain stimulation?

Deep brain stimulation (or DBS) is a treatment method that involves embedding electrodes into the brain to help modulate the brain activity involved in movement.

It is a prodcedure that is usually offered to people with Parkinson’s who have excessive tremor or debilitating dyskinesias.

First introduced in 1987, deep brain stimulation consists of three components: the pulse generator, an extension wire, and the leads (which the electrodes are attached to). All of these components are implanted inside the body. The system is turned on, programmed and turned off remotely.

Shahlaie_DBS_Illustration-full

Source: Ucdmc

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Gene therapy: VY-AADC01 vs AXO-Lenti-PD

 

Future generations may treat conditions like Parkinson’s with DNA rather than drugs. By manipulating the DNA within a given cell, researchers can cause that cell to generate proteins that they usually do not produce.

This technique is called gene therapy, and it is currently being clinically tested in people with Parkinson’s.

Recently, one biotech firm (Voyager Therapeutics) has provided new data on an ongoing clinical trial and another company (Axovant Sciences) has announced the initiation of a clinical study.

In today’s post, we will discuss what gene therapy is, evaluate what the first company has achieved, and compare it with the clinical trial that is just starting.

 


Source: 2018.myana

At the annual American Neurology Association (ANA) meeting this year, we got an update on an ongoing clinical trial for Parkinson’s being conducted by a company called Voyager Therapeutics.

The biotech firm presented data at the meeting regarding their gene therapy approach for Parkinson’s.

What is gene therapy?

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Voyager Therapeutics update

This week a biotech company called Voyager Therapeutics provided an update regarding a gene therapy approach for people with severe Parkinson’s.

Gene therapy is an experimental therapeutic approach that involves inserting new DNA into cells using a virus. The introduced DNA can help a cell to produce proteins that it usually wouldn’t  produce, and this can help to alleviate the motor features of Parkinson’s.

In today’s post we will discuss what gene therapy is, what Voyager Therapeutics is trying to do, and outline what their update reported.


There are 4 phases to the clinical trial process of testing new treatment for use in humans:

  • Phase I determines if a treatment is safe in humans (this is conducted in an ‘open label’ manner)
  • Phase II ‘double blindly’ assesses in a small cohort of subjects if the treatment is effective
  • Phase III involves randomly and blindly testing the treatment in a very large cohort of patients
  • Phase IV (often called Post Marketing Surveillance Trials) are studies conducted after the treatment has been approved for clinical use

(‘Open label’ refers to both the investigator and the participants in a study knowing what treatment is being administered; while ‘double blind’ testing refers to studies in which the participants and the investigators do not know whether the participant is receiving the active treatment or an inert control treatment until the end of the study).

Based on the successful completion of their Phase I clinical trials for their gene therapy treatment called VY-AADC (Click here to read more about this), Boston-based biotech firm Voyager Therapeutics approached the US Food and Drug Administration (FDA) with the goal of shifting their clinical trial programme into Phase II testing.

What is gene therapy?

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Happy birthday: Silverstein Foundation

Over the last 12 months, the Silverstein Foundation has quickly established itself as a major focused force in the fight against Parkinson’s.

And when I say ‘focused’, I mean ‘focused’ –  the foundation is “actively pursues and invests in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in glucocerebrosidase (GBA) mutation carriers”.

But the output of this effort may well have major benefits for the entire Parkinson’s community.

In today’s post, we will discuss what GBA is, how it functions inside cells, its association with Parkinson’s, and what all of this GBA focused research being funded by the Silverstein Foundation could mean for the Parkinson’s community.


Jonathan Silverstein. Source: Forbes

This is Jonathan Silverstein.

He’s a dude.

He is also a General Partner and a Co-Head of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.

In February 2017, he was diagnosed with Parkinson’s disease at just 49 years of age.

Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation.

They raised $6 million from donors and then provided another $10 million of their own money to fund the endeavour, which has funded a dozen research projects and started a new company called Prevail Therapeutics (we’ll come back to this shortly).

Source: Businesswire

The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”

And it seeks to address this by achieving three goals:

  1. to find a way to halt the progression of Parkinson’s with GBA.
  2. to identify regenerative approaches to replace the damaged/lost cells
  3. to find preventative measures

What is ‘GBA’?

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Voyager Therapeutics: Phase I clinical trial update

Today biotech company Voyager Therapeutics announced an update on their ongoing phase Ib clinical trial. The trial is evaluating the safety and tolerance of a gene therapy approach for people with advanced Parkinson’s.

Gene therapy is a technique that involves inserting new DNA into a cell using viruses. In this clinical trial, the virally delivered DNA helps the infected cell to produce dopamine in order to alleviate the motor features of Parkinson’s.

In today’s post we will discuss what gene therapy is, review the new results mentioned in the update, and look at other gene therapy approaches for Parkinson’s.



Source: Baltimoresun

Voyager Therapeutics is a clinical-stage gene therapy company that is focused on treatments for neurological conditions, such as Parkinson’s. Today the company announced an update of their ongoing Phase 1b trial of their product VY-AADC01 (Click here to see the press release).

VY-AADC01 represents a new class of treatment for Parkinson’s, as it is a form of gene therapy.

What is gene therapy?

The gene therapy involves introducing a piece of DNA into a cell which will cause the cell to produce proteins that they usually do not (either by nature or by mutation). The DNA is artificially inserted into cells and the cell’s protein producing machinery does the rest.

Source: Yourgenome

How does gene therapy work?

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2017 – Year in Review: A good vintage

At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective. 

2017 has been an incredible year for Parkinson’s research.

And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.

In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)


The number of research reports and clinical trial studies per year since 1817

As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.

The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).

PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.

That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.

And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.

So what happened in 2017? Continue reading