Biotech Strategy Blog

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Posts tagged ‘Michael J Fox Foundation’

Drug development for neurodegenerative brain diseases such as Parkinson’s or dementia, of which Alzheimer’s is the most common form, needs to focus on patients early in the disease, not those where brain damage has already occurred.

Diagnosing and treating patients more effectively earlier will, even if you aren’t able to instigate a cure, offer the ability to modify the disease progression and slow or delay when brain damage occurs.  In the case of Alzheimer’s, once the amyloid plaques (tangles of misshapen proteins) have accumulated in nervous tissue, it has so far been impossible to untangle or remove them.

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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.

Yesterday, I posted the first part of my interview with Dr Todd Sherer, Chief Program Officer at the Michael J Fox Foundation.

Next week, I will be posting the second part of the interview that discusses the significant research the foundation is funding on biomarkers that can help the diagnosis of the disease and monitor its progression.

If you are interested in learning more about the latest developments around Parkinson’s disease biomarkers, then you may wish to consider the April 27, 2011 webinar from the American Association for the Advancement of Science (AAAS) on the “Early Detection of Parkinson’s Disease: The Challenges and Potential of New Biomarkers.”

Moderated by Dr Todd Sherer, the webinar will discuss the only FDA approved biomarker, DaTscan that provides for imaging of dopamine transporters at dopaminergic nerve terminals in the nigrostriatal pathway.  It will also discuss the Parkinson’s Progression Markers Initiative (PPMI) that the foundation is funding.

Today is the deadline to take advantage of the early bird discounts on offer for this webinar.

Biotech Strategy blog recently had the privilege to do a phone interview with Dr Todd Sherer, the Chief Program Officer of the Michael J Fox Foundation.  In this two- part interview, Pieter Droppert asks what the MJFF approach to research funding is and what the future holds for Parkinson’s disease research?


Part 1:  Research Funding

Research funding is key to science. Without it there would be no translational medicine that takes basic research and turns it into clinical applications that benefit humans.  One organization that is making a difference and bridging the gap between patients and research is the Michael J Fox Foundation (MJFF).

Biotech Strategy Blog: What does a Chief Program Officer do?

Dr Sherer: My role as Chief Program officer is to lead the research efforts at the Michael J Fox Foundation. My background is as a neuroscientist so I have a PhD in neuroscience, and my lab work was in Parkinson’s disease before I joined the foundation.  At the foundation we have a number of additional scientists, seven in total. They work closely with people with business backgrounds in a collaborative way.  What we are trying to do is apply business principles to scientific research.  So, select the best scientific projects and then design them in a way where there are deliverables, milestones and goal directed research with the ultimate aim to improve treatment for Parkinson’s patients.

Biotech Strategy Blog: MJFF receives 800 grant applications a year, what is your approval process, is it similar to the National Institutes of Health?

Dr Sherer: It is modeled after the NIH process with the one main difference being that our internal scientific staff has a proactive role in making the final funding decisions.  We take the peer review panel to help us evaluate, but the ultimate decision lies with our internal staff.  We do a rapid turn around of those reviews so from receiving an application to funding is usually for us 3 to 4 months total.

Biotech Strategy Blog: What business principles do you use in managing the research that you fund?

Dr Sherer: One of the main things we do with every grant we make is laying out from the beginning: what is actually the goal of that grant. This probably seems logical, but actually a lot of scientific research is very open ended – it is kind of “let me see what I discover”. But we are really trying to define from the beginning: what are we trying to accomplish? Then what we can do is set milestones along the way to that goal to make sure during the course of the project, we are making the progress we need to achieve that goal.

Biotech Strategy Blog: Are grant payments linked to performance?

Dr Sherer: The payments for the grants are all tied to the milestones, and I would say that we are realistic in that we are experienced in how research works.  This is not manufacturing, and we know that you can have the best plan, but it is all based on a hypothesis and things can come up in the course of the research. Our scientific staff here will always work closely with those grantees to make the rational adjustments in the plan based on what we are learning along the way.

Biotech Strategy Blog: In addition to the grant applications that you receive, does the Michael J Fox Foundation initiate its own projects?

Dr Sherer: Yes. We have identified specific priority topics within Parkinson’s disease, whether they be specific therapeutic targets, or something like a biomarker, where we are more proactively working with the research community to develop projects to address critical challenges in those areas.  We also do conduct some research using a virtual research model where the scientists here may outsource some work with contract research organizations.  We have been particularly doing that around research tools so that we can make those tools widely available to our researchers — things like antibodies, plasmids, vectors —  we want to quickly get these made without any licensing or intellectual property restrictions and then make them broadly available to the research community.

Biotech Strategy Blog: Why does MJFF fund research by commercial entities e.g. biotechnology & biopharmaceutical companies?

Dr Sherer: The goal of the foundation, the goal of all the research that we are supporting is to develop new therapies for Parkinson’s disease patients.  We understand that will involve all players in the research space, so it involves academic researchers.  But really to convert those discoveries into therapies for people, we want to proactively engage and interact with the biotech and biopharma community because they are the ones who in the end make the therapies for patients.  About 5 or 6 years ago we decided to more proactively outreach to the biopharma community to determine: if we provided funding, could we induce more companies to work in Parkinson’s disease or accelerate their work in Parkinson’s disease.

Biotech Strategy Blog: What types of biotech & biopharma companies do you fund?

Dr Sherer: There are some companies that have worked in related diseases, like another neurodegenerative disease, and our  funding allows them to apply that technology to Parkinson’s disease.  Another category would be a platform type of company that we have supported, where they could really go to any disease, but the Fox funding allows creates a rationale to choose Parkinson’s.  Then we have funded some companies who are interested in Parkinson’s but for budgetary reasons have made some trade-offs in the design of that study. With additional funding from the foundation they can increase the sample size, hone the end points or what have you, to really make that study more robust.  We have seen a lot more companies working in Parkinson’s as a result of this outreach.

Biotech Strategy Blog: Do you take any rights in any commercial research you fund?

Dr Sherer: In most of our projects we do not have any stipulation like that, particularly in the case where we are funding some preclinical testing. That said, in our largest, multi-million dollar grants, particularly those in late-stage clinical development, we usually have an agreement that there is a return payment after some amount of sales.  That is more the exception than the rule.

Biotech Strategy Blog: Thank you

Part 2 of this interview with Dr. Todd Sherer, Chief Program Officer of the Michael J. Fox Foundation, will provide insight on the current status of research into Parkinson’s disease, and what we can expect the future to hold?

Earlier this month the Michael J Fox Foundation (MJFF) announced that Vancouver based Allon Therapeutics had been able to improve motor function and brain pathology in a mouse model of Parkinson’s disease (PD).

MJFF funded this research with Allon Therapeutics. The preclinical study results are published in the Journal of Molecular and Cellular Neuroscience.

What makes this data interesting is that it adds further support to the potential efficacy of the company’s lead product, davunetide, in a wide range of neurodegenerative disorders.

Davunetide (AL-108) is a microtubule-interacting peptide based on an eight amino acid sequence, Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, single letter code NAPVSIPQ (NAP) derived from activity-dependent neuroprotective protein (ADNP). It has been shown to have neuroprotective properties.

Davunetide can be administered by IV or intranasally and crosses the blood/brain barrier. It is effective at promoting neurite growth, restoring transmission between nerve cells and untangling some of the damage seen in neurodegenerative disorders such as Alzheimer’s disease. References to the scientific publications and mechanism of action can be found on the Allon Therapeutics website.

Currently it is being developed for Alzheimer’s disease (AD), schizophrenia cognitive impairment and frontotemporal dementia (FTD). Davunetide is in a phase 3 clinical trial for progressive supranuclear palsy (PSP), a subtype of FTD.

The company’s strategy is to pursue a fast-track to market in a small indication such as PSP. This is makes a lot of sense for a small biotechnology company with limited funding.  Successful approval in PSP will significantly increase the value of the company and improve the terms of any future licensing/partnering deals.

The hope for davunetide is that it will prevent disease progression in disorders such as AD and provide neuroprotective prophylaxisis prior to surgery that carries a high risk of memory loss e.g. heart bypass and coronary artery graft surgery (CABG).

While davunetide may not be a cure for AD, being able to slow down disease progression is something that has considerable value.  Given that new imaging biomarkers are likely to provide the opportunity to detect AD much earlier, the market opportunity for early treatment is set to increase.

Many families and caregivers would welcome a drug that delays further cognitive decline and memory loss in their loved ones.

On the basis of the promising preclinical results, I think we can expect to see further clinical research on davenutide in Parkinson’s Disease.

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