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Neurotrophic factors – like Glial cell line-derived neurotrophic factor (or GDNF) – hold great hope for regenerative therapy in Parkinson’s research. New research, however, indicates that simply injecting the protein into the brain may not be enough.
Scientists at Rush University Medical Center (in Chicago) conducted a postmortem analysis of brains from people who passed away with Parkinson’s and made an intriguing discovery.
They found that many of the remaining dopamine neurons appear to not be producing a protein called Ret, which is required for GDNF signaling. In addition, other components of GDNF signaling pathway were missing.
In today’s post, we will review the background of this new study, outline what the study found, and discuss the implications of the research.
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GDNF. Source: Wikipedia
Glial cell line-derived neurotrophic factor (or GDNF) is a topic that gets a lot of reader attention on the SoPD. It is a tiny protein that holds great hope for the Parkinson’s community in terms of providing a potential neuroprotective and regenerative therapy.
GDNF is a type of neurotrophic factor, which are small naturally-occurring proteins that nurture neurons and support their growth. There are different kinds of neurotrophic factors, and the testing of some of them in preclinical models of Parkinson’s has generated encouraging results (particularly in the case of GDNF – click here to read a previous SoPD post on this topic).
But the translation of those initial results in cell culture and animal models of Parkinson’s has been difficult in clinical trials of neurotrophic factors.
This has led to many questions being asked within the research community about the nature of biological signaling pathways involved with neurotrophic factors and whether they might be affected in Parkinson’s.
The majority of the neurotrophic factors that have been tested in models of Parkinson’s and in clinical trials for Parkinson’s belong to a branch that requires the RET signaling pathway to be available to have their neuroprotective effect.
What is the RET signaling pathway?
Continue reading “What is GDNF without RET?”
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News today of two biotech companies merging did not cause much of a ripple in the media, but the wider implications of the move are rather significant for Parkinson’s.
Today it was announced that Brain Neurotherapy Bio (BNB) is going to merge with Asklepios Biopharmaceutical (aka AskBio). BNB are currently clinically testing a GDNF gene therapy approach for Parkinson’s, and AskBio is a subsidary of the large Pharmaceutical company Bayer.
This is the same ‘Bayer’ that last year bought BlueRock Therapeutics – a biotech company focused on cell transplantation for Parkinson’s (Click here to read a previous SoPD post about that).
In today’s post, we will discuss what BNB are doing and why this merger is particularly interesting.
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One of the themes this year on the SoPD website has been an effort to highlight (and encourage) more focus on alternative restorative therapies for Parkinson’s. There are a lot of different approaches exploring very different methods of slowing the progression of Parkinson’s, but most of the current clinical efforts investigating restorative therapies are oriented solely around cell transplantation.
What we really need are some novel strategies for replacing what is lost and encouraging re-growth from cells that remain.
Most of the SoPD posts exploring this idea during 2020 have been looking at very blue sky ideas (Click here, here, here and here to read some examples). But we have also been keeping an eye on biotech efforts in this domain, and today we received some interesting news which involved the merger of two biotech companies.
The merger occurred between Asklepios Biopharmaceutical (aka AskBio) and Brain Neurotherapy Bio.
ASKBio is a “gene therapy company dedicated to improving the lives of patients with rare diseases and other genetic disorders“. Gene therapy involves using DNA to treat medical conditions, rather than drugs. The DNA is usually delivered to the tissue requiring correction by carefully engineered viruses.
Brain Neurotherapy Bio is also a gene therapy biotech company that is currently clinically testing a GDNF gene therapy approach for Parkinson’s.
What is GDNF?
Continue reading “Bayer doubles down on Parkinson’s?”
In 2013, a biotech company called Ceregene reported disappointing results from their experimental gene therapy clinical trial for Parkinson’s. The data from the study suggested that the therapy had no clinical effect on the progression of Parkinson’s (Click here to read the press release).
Today, however, researchers associated with that biotech company have published a new report that suggests that the treatment had beneficial effects in the brain, but not enough of it was delivered.
The treatment was a gene therapy approach (which involves using DNA rather than drugs to treat medical conditions), and it involved a protein called neurturin.
In today’s post, we will discuss what neurturin is, we will review what this new study found, and consider what the implications could be for future gene therapy trials in Parkinson’s.
Reanalysing clinical trial data (called post-hoc analysis) provides a very useful way of generating new hypotheses even if the initial study did not reach its primary endpoint (that is to say the study did not demonstrate a successful outcome. Post-hoc analysis must be handled carefully, as the findings of such investigations can be viewed as selective ‘cherry picking’ of interesting outcomes. They will need to be tested to determine if they are real effects.
Even more important than post-hoc analysis, however, is following up participants who took part in a trial to see if there were any long-term benefits from the treatment. I often wonder how much important data is lost after a clinical trial simply becomes there is no long term follow up and study investigators lose track of participants as they drift away.
Precious nuggets of information can be gained from long-term analysis. And this week we saw a really interesting example of this.
Here is the research report:
Title: Long-term post-mortem studies following neurturin gene therapy in patients with advanced Parkinson’s disease.
Authors: Chu Y, Bartus RT, Manfredsson FP, Olanow CW, Kordower JH.
Journal: Brain. 2020 Mar 1;143(3):960-975.
PMID: 32203581 (This report is OPEN ACCESS if you wouldl like to read it)
In this study, the researchers were looking at postmortem brain sections from 2 participants who took part in a clinical trial investigating a treatment called neurturin.
What is neurturin?
Continue reading “Something new for neurturin”
Neurotrophic factors are naturally occuring proteins that help to keep neurons alive, provide a supportive environment, and encourage growth.
For a long time, researchers have been exploring methods of utilising the power of neurotrophic factors in regenerative strategies for neurodegenerative conditions, like Parkinson’s.
Today, the biotech firm Herantis Pharma announced topline results of their Phase 1/2 clinical trial of the neurotrophic factor Cerebral Dopamine Neurotrophic Factor (or CDNF).
In today’s short post, we discuss what CDNF is, explore what the trial involved, and consider what the
It is cold this time of year in Helsinki, but there will be some warm smiles there today.
A small biotech firm called Herantis Pharma has announced the topline results of their Phase 1/2 clinical trial exploring the safety and tolerability of a treatment called CDNF.
What is CDNF?
Continue reading “The Phase 1/2 CDNF topline results”