Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘blood brain barrier’

This month is Parkinson’s awareness month.  Following on from my recent interview (that you can read here & here) with Dr Todd Sherer of The Michael J. Fox Foundation for Parkinson’s Research, I was interested to read about progress being made on the road to towards targeted therapies.

The April 2011 issue of Nature Chemical Biology reports the development of a selective inhibitor of leucine-rich repeat kinase 2 (LRRK2), a gene that is mutated in some patients with Parkinson’s disease.

The team of researchers from Dana-Farber Cancer Institute, Harvard Medical School, University of Dundee, Scripps Research Institute and ActivX Biosciences applied a novel, screening strategy focused on selectively inhibiting LRRK2.

The result was the identification of LRRK2-IN-1, a novel analog that inhibits both wild-type and mutant LRRK2 kinase activity. The team confirmed the activity of LRRK2-IN-1 using human lymphoblastoid cells from a Parkinson’s disease patient with the LRRK2 mutation.

Unfortunately, LRRK2-IN-1 was unable to cross the blood-brain barrier, which means that it is not suitable for Parkinson’s disease.  However, this research is progress on the road to LRRK2 inhibition and the development of a targeted therapy in the future.

Moving forwards Parkinsons’ researchers may wish to consider combining new small molecules with nanoparticles that are able to cross the blood-brain barrier; this may be the way to deliver targeted therapies to the brain.


ResearchBlogging.orgDeng, X., Dzamko, N., Prescott, A., Davies, P., Liu, Q., Yang, Q., Lee, J., Patricelli, M., Nomanbhoy, T., Alessi, D., & Gray, N. (2011). Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2 Nature Chemical Biology, 7 (4), 203-205 DOI: 10.1038/nCHeMBIO.538

Biotech Strategy Blog recently had the privilege to  interview Dr Todd Sherer, Chief Program Officer of the Michael J. Fox Foundation.

In the second part of a two-part interview, Pieter Droppert asks what the future holds for Parkinson’s disease research? You can read the first part of the interview here.

Part 2:  Understanding Parkinson’s disease

Biotech Strategy Blog: Why don’t we know what the cause of Parkinson’s disease is?

Dr Sherer: What we know about the cause of Parkinson’s disease is that, in most cases, it is an interaction between genes and environment that really covers a broad definition. In the last 10 years we have made a lot of advances in knowing the genetics of Parkinson’s disease and there are at least 15 different genes that have now been linked to the cause of Parkinson’s.

There are two big challenges in trying to define the cause of Parkinson’s.

First, there’s probably more than one “cause” of Parkinson’s disease.  For example, we know in certain people if they have a specific genetic mutation, they can get Parkinson’s disease. We also know of cases where people acutely exposed to an environment toxin called MPTP got Parkinson’s disease instantly.  There is probably an array of different triggers that can ultimately lead to Parkinson’s, given that it’s a late onset chronic disease.  So it has been very hard to pinpoint one particular cause.

Second, Parkinson’s disease can have a lot of variability in individuals — some people can have early onset, some later onset.  Some have tremor as the dominant symptom, others posture and walking problems.  It is therefore possible that there could be subsets or subtypes of Parkinson’s disease. That makes it difficult when historically we have looked for a common cause for a broad array of clinical symptoms.

Biotech Strategy Blog: Where do you see the next major breakthrough coming in the next 5 to 10 years?

Dr Sherer: The understanding of the genetics of Parkinson’s will certainly form the building blocks of some future breakthroughs.  Now that we have very tangible therapeutic targets that we know can cause Parkinson’s, it makes a much more rational directed drug development program.  Before those genes were found, a lot of Parkinson’s drug development was focused on oxidative stress, inflammation or mitochondrial dysfunction, all of which contribute to Parkinson’s, but present many different targets.

We have now found a gene called LRKK2, and two to five percent of all Parkinson’s patients get the disease through a mutation in this gene. It is a protein kinase, making it a potentially very druggable target.   There is a lot of interest in these new targets for Parkinson’s that are moving through preclinical research, so I think this knowledge from the genetics is spearheading a new era in Parkinson’s research.

Biotech Strategy Blog: Do you think targeted therapies will have an impact?

Dr Sherer: The hope is that while these new therapies may be targeting genetic causes that are present in a subset of people with the disease, given common mechanisms in the cause of the disease, they may have applicability to all Parkinson’s patients. That remains to be determined, but there is some precedent that may be the case.

Biotech Strategy Blog: What role do you think biomarkers will play in the detection and treatment of Parkinson’s disease?

Dr Sherer: Biomarkers are a real focus area for the Foundation and I think they are a critical piece of the puzzle for a couple of reasons.  Parkinson’s is a difficult disease to diagnose; there is no definitive diagnostic test, so it ends up a clinical diagnosis. Getting a biomarker that could help better confirm the diagnosis would allow people to get the correct treatment earlier in their disease or at least see the correct doctor earlier in their disease.

For all the treatments we have for Parkinson’s, we don’t currently have any that is disease modifying, i.e. one that will slow, delay or reverse the underlying progression of the disease.  While people can be treated for some of the motor symptoms, the disease process continues and there is additional damage to the regions of the brain affected in the disease.  Over time the medicines no longer work because the progression has continued.  We really want a therapy that can alter that progression.

Biomarkers could help speed the development of therapies with potential to alter disease progression, because we would have a way to determine whether the treatments we are testing are actually impacting the disease course. This is something we don’t have a way to do today.  Developing biomarkers that allow us to track the disease and potentially turn back the clock on the disease by identifying people earlier in the process, are both critical pieces.

Biotech Strategy Blog: Given the challenges of getting drugs across the blood/brain barrier, does nanotechnology open up opportunities for the future?

Dr Sherer: The blood/brain barrier is critical for Parkinson’s and other neurological diseases and even within the brain targeting therapies to a particular subset of the region of the brain is also critical.  Any technology that could be used to improve that would be very important.

Biotech Strategy Blog: What take home message would you give to those involved with Parkinson’s research and those suffering from the disease?

Dr Sherer: That’s a tough one. Everyone at the Foundation comes to work every day trying to figure out how can we solve this problem of Parkinson’s disease?  How can we find the right researchers, the right projects that will allow us to move the progress forward to developing new therapies for the disease?

I would encourage researchers to reach out to us and work with us as partners in their research.  We have a lot of knowledge, access to a lot of the experts, research tools that could help accelerate their research, not only from a funding perspective, but also from a collaborative perspective.

For the patients, a similar message that we are working on this problem.  We are dedicated to it and are determined to make improvements in treatment. We want patients to be involved in this process.  The research requires all engaged people and the patients have a lot to contribute.  They live with disease, know what the biggest problems they face are.  They could participate in research to help us answer the questions we have.

It will take all interested parties working together to solve this very difficult disease.

Biotech Strategy Blog: Thank you

Further information on the research the Michael J Fox Foundation is supporting and how you can get involved can be found on the foundation’s website.

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