Making a strong case for GCase

Novel therapies are increasing being developed to focus on specific subtypes of Parkinson’s. The hope is that if they work on one type of Parkinson’s, then maybe they will also work on others.

Many of these new experimental treatments are focused on specific genetic subtypes of the condition, which involve having a specific genetic variation that increases one’s risk of developing Parkinson’s.

Increasing amounts of data, however, are accumulating that some of the biological pathways affected by these genetic variations, are also dysfunctional in people with sporadic (or idiopathic) Parkinson’s – where a genetic variation can not explain the abnormality.

In today’s post, we will review some new research that reports reductions in a specific Parkinson’s-associated biological pathway, and discuss what it could mean for future treatment of the Parkinson’s.


Source: Medium

I was recently at a conference on Parkinson’s research where a prominent scientist reminded the audience that just because a person with Parkinson’s carries certain genetic risk factor (an error in a region of their DNA that increases their risk of developing Parkinson’s), does not mean that their Parkinson’s is attributable that genetic variation. Indeed, lots of people in the general population carry Parkinson’s associated genetic risk factors, but never go on to develop the condition.

And this is a really important idea for the Parkinson’s community to understand: Most of the genetics of Parkinson’s deals with ‘association’, not with ‘causation’.

But that begs the question ‘if we do not know that these errors in our DNA are causing Parkinson’s, then why should we be trying to develop therapies based on their biology?’

It is a fair question (it is also a very deep and probing question to start a post off with!).

The genetics of Parkinson’s has been extremely instructive in providing us with insights into the potential underlying biology of the condition. We have learnt a great deal about what many of the biological processess thatare associated with these genetic risk factors, and (yes) various experimental therapies have been developed to target them.

These novel treatments are clinically tested in the hope that they will have beneficial effects not just on individuals carrying certain genetic risk factors, but also on the wider Parkinson’s community.

And recently, there has been increasing evidence supporting this possibility. Some of the biological pathways associated with these genetic mutations appear to also be abnormal in people with Parkinson’s who do not carry the genetic variation.

What do you mean?

Continue reading “Making a strong case for GCase”

Say it with me: Farn-e-syl-trans-fer-ase

 

Not a week goes by without some new peice of research suggesting yet another biological mechanism that could be useful in slowing or stopping Parkinson’s. This week researchers in Chicago reported that pharmacologically inhibiting a specific enzyme – farnesyltransferase – may represent a novel means of boosting waste disposal and helping stressed cells to survive.

A number of farnesyltransferase inhibitors are being developed for cancer, and there is the possibility of repurposing some of them for Parkinson’s.

In today’s post, we will discuss what farnesyltransferase is and does, what the new research report found, and we will consider whether inhibition of this biological pathway is do-able for Parkinson’s.

 


Source: Knowledgepathinc

I am in the midst of preparing the “end of year review” and “road ahead” posts for 2019/2020 (they take a while to pull together). But it is already extremely apparent that we have an incredible amount of preclinical data piling up,…. and a serious bottleneck at the transition to clinical testing.

It is actually rather disturbing.

Previously this was a concern, but going forward – as more and more novel preclinical work continues to pile up – one can foresee that it is going to be a serious problem.

But there is just SOOOO much preclinical data on Parkinson’s coming out at the moment. Every single week, there is a new method/molecular pathway proposed for attacking the condition.

A good example of this frenetic pace of preclinical research is a recent report from researchers in Chicago, who discovered that a farnesyltransferase inhibitor could be beneficial in Parkinson’s.

Farne…syl… what?

Continue reading “Say it with me: Farn-e-syl-trans-fer-ase”