A shadowy place: the concept of disease interception and what you should know about it.

“What happens in that time, that shadowy place?” - Michael Jay Fox

At the age of 29 Michael Jay Fox’s pinky started to twitch. This was when his Parkinson’s first manifested symptomatically. But Fox wants to know what happened before his pinky began to twitch (Ref stat article).

Michael J Fox is a famous 80’s actor who after he developed Parkinson’s started the Michael J Fox Foundation which is focused on supporting Parkinson’s research.

Fox sees the potential to intervene before symptoms manifest. Such an approach has come to be called disease interception.

We’ll go into later what Fox is doing to make interception for Parkinson’s disease a reality, but first its helpful to better understand what interception is and why it is an important concept.

What is interception?

The Janssen World Without Disease Accelerator defines interception as

…intervening earlier than today’s clinically accepted point of diagnosis.

The European Federation of Pharmaceutical Industries and Association (EFPIA) confines interception to intervening when there is an absence of symptoms.

However, that definition would exclude individuals who have very mild symptoms that would otherwise not rise to the point of awareness or diagnosis.

Nevertheless interception is held forth as new approach that differs from prevention.

Interception is about intervening with a treatment whereas prevention may simply be about behavioral modifications, or public health measures for a whole population.

Interception is more focused on the individual as opposed to a population level.

So, for example chronic obstructive pulmonary disease (COPD) is a condition where there is destruction of lung tissue resulting in loss of large areas of the lungs - emphysema.

Everyone has a lot of overcapacity in your lungs, the process of destruction is likely going on for years before individuals with COPD become short of breath.

If we can intervene in the early stages of the process it could make an enormous difference.

A meaningless buzz phrase?

Narchi and Winkler (1) argue that interception is a commercial construct and that we should use the phase

early and targeted secondary prevention by treatment.

First, off their fear of interception being a commercially motivated concept is misplaced.

Just because industry is interested in something does not automatically disqualify it as being legitimate.

Yes of course industry sees the potential to have a wider market where disease is treated early on, however that is also the interest of just about every other stakeholder from the patient to their clinicians and even including payers as interception could transform life long treatment for a chronic condition to a temporary outlay that prevents the likely more costly development of full blown symptoms.

Of course the opposite might be true if interception means life long treatment. And we know that buzz phrases can drive a whole field without there being much evidence behind the buzzy concept.

What is great about the term interception is that it is easier to understand and it reflects an optimistic outlook.

Talking about “early and targeted secondary prevention by treatment” is cumbersome and more opaque for those without a medical background.

Is early disease different than disease in the later stages?

An important consideration is if early disease is fundamentally different than later stage disease or a difference in degree?

It is conceptually more comfortable to think about early disease as being just a difference of degree. After all it is simpler to imagine that late stage disease more of what caused the disease in the first place. But is that just a convenient way of thinking?

Many late stage diseases are characterized by significant tissue injury, outright destruction and overactive repair.

Would we expect the molecular environment to be different than in early disease where there may not be any or very little tissue damage?

Of course you can quickly degrade into semantics of what is early disease. Is it a risk state where an individual is at greater risk for developing a disease or is it an early phase of the disease course. Of course it is highly dependent upon the type of disease.

James Peyer the CEO of Cambrian Biopharma points that its easy to cure cancer in mice when the cancer is not at an advanced stage :

If we treat the cancer early you get 100% cure rates but that does not translate into effective therapies in people with advanced cancer.

Yet preclinical models that represent cancer at an early stage are of little interest as clinical treatment is nearly always in the more advanced stages.

So, new therapies tested in milder preclinical models are doomed to fail in the clinical setting.

It is fascinating how the current clinical treatment paradigm determines how effective your preclinical model is in predicting the success or failure of a new treatment.

Simply because the prevailing paradigm was to treat late stage cancer, models of milder forms of disease are nearly irrelevant.

The entangled nature of clinical treatment paradigms and relevant preclinical models says something about the imperfect world of preclinical models.

It also speaks to the utmost importance of not working in a bubble, but rather engaging with different stakeholders such as clinicians or patients themselves.

Peyer and his colleagues at Cambrian Biopharma are banking on the fact that they can cure cancer in mice to bring therapeutics that are given in the early stage of disease or even before the disease process begins to market.

Their long term vision is to develop and market ways to slow down or reverse the aging process.

However, there is currently no regulatory framework for getting an anti-aging therapeutic approved.

So, they will go for a step wise approach choosing the right indications to prove safety and efficacy and then do the anti-ageing studies.

They are aiming for the ultimate form of interception (or prevention if you want to go with the less inspiring terminology).

But if companies like Cambrian Biopharma are going to be successful they will need early disease to be just a mini-version of full blown disease.

This is more so the case for cancer.

An earlier stage cancer is likely to be similar to late stage tumors. Although there is plenty of evidence highlight the effects of the tumor niche, and environmental factors such as the microbiome.

The bottom line is that we do not know enough about early disease.

It is as if we need to rewind the clock and do the work to understand the mechanisms of early disease or pre-disease states.

However, we can be much more efficient at sorting out those mechanisms.

The technology and the ability to even understand what genes are being transcribed at the single cell level coupled with the ability to measure the levels of thousands of proteins is tantalizing.

Yet for that to happen their needs to be interest in studying early disease and ultimately interest in investing in development programs for therapies that aim to intercept.

Changing the paradigm for how we approach disease is a multi-stakeholder problem. It is a nearly a ‘wicked problem’

Avoiding working in a bubble

The summer after the first year in medical school I worked in a lab that was trying to develop immunotoxins for treating cancer.

The lab was a combination of a clinical researcher and a PhD researcher. The researcher’s wife, who also worked in the lab, would say that her husband would be off purifying gnat wings if it was not for the direction and focus that the physician scientist was bringing to the lab.

That synergy has always formed a model in my mind of how research in the life sciences should be done.

Such synergies have the potential to avoid situations like what happened with preclinical cancer model studies.

Those kinds of relationships are also important for gaining the acceptance of new approaches.

You could develop the perfect therapy to intercept a disease early, but if the clinicians, the payers and most importantly the patients don’t believe in treating disease early it will be a wasted effort.

Think about vaccine hesitancy. What sort of hesitancy will there be to intervene early just to reduce the chances that what is now and inapparent disease does not develop into something bigger?

We do have examples such as treating hypercholesterolemia.

Of course if you define hypercholesterolemia as a disease that needs to be treated then you are not trying to prevent cardiac disease. You are treating an active condition.

This all just illustrates the complexities of taking aim at disease interception.

The perfect bubble buster

The perfect bubble buster is a consortium project.

By nature consortium projects are multi-stakeholder in composition and they tend to be ambitious.

Consortium projects are perfect for the types of problems where it unclear how to address the problem and uncertain what you can achieve, otherwise known as wicked problems.

And as mentioned before shifting the current treatment paradigm towards interception is pretty much a wicked problem. It turns out that that twitching pinky spawned an initiative that is making this problem much less wicked.

The Parkinson’s Progression Marker’s initiative

Michael J Fox’s curiosity about the shadowy place that preceded his first symptoms helped fuel the formation of the Parkinson’s Progression Markers Initiative (PPMI) in 2010.

PPMI is a comprehensive natural history study that aims to identify biomarkers for the progression of Parkinson’s.

The link between Fox’s passion and the resulting PPMI is a good example of how emotion can be an important driver of innovation.

PPMI is set up as a consortium with a hub and spoke structure. It has over 50 clinical sites and consists of a cluster of working groups and study cores overseen by a Steering Committee.

The mission of PPMI is “to profile biological and clinical changes across the spectrum of disease with an emphasis on signals in at-risk individuals to identify the disease and intervention points as early as possible.”

What’s remarkable is that in April 2023 the PPMI announced the identification of a biomarker for Parkinson’s that can detect Parkinson’s in individuals who have to be diagnosed (2).

Interception and funding.

The Strategic Research Agenda for the Innovative Health Initiative (EU funded public/private partnerships) mentions interception in its second objective:

Integrate fragmented health R&I efforts by bringing together health industry sectors and other stakeholders, focusing on unmet public health needs, to enable the development of tools, data, platforms, technologies and processes for improved prediction, prevention, interception, diagnosis, treatment and management of diseases, meeting the needs of end-users.

Biomarkers for interception is also mentioned as an output of the first objective.

While the term interception is not directly used, the Horizon Europe Health Work Programme 2023-2024 uses variations of the work prevention 139 times in the document.

This highlights why it is important to pay attention to emerging concepts like interception.

What you can do

Interception has implications for how you approach research and innovation.

Like a lot of other concepts, i.e. precision medicine there is a risk that the adoption of interception as commonplace clinical concept will take time.

Here are four things you should do.

1). Use the term ‘interception’.

The term interception is more accessible to all stakeholders than secondary prevention with treatment

Communication is about more than having technically correct phrasing. The understanding of the receiver of the message is of paramount importance.

Communication is most impactful when it inspires and the idea that we are going to intercept disease is inspiring

Use the term interception in your talks, in your papers as well as informally. Doing so will also help you to understand the term and its implications better.

2) Make interception your strategy.

Its clear that interception is a growing trend and trends are where you can find synergies and resources

Resources and synergies make it easier to do ambitious projects and achieving ambitious goals that improve the lives of patients is why we are all doing what we are doing.

How? Use interception as a focusing concept - it is a strategy it is a choice and choice to focus your efforts.

3) Promote the concept of interception

Trends like interception can fade over time.

To make interception an accepted approach reality a broad community of stakeholders needs to embrace the concept

Talk about interception, write about interception and gather data on interception. Just understanding early disease will help to

4) Build the concept of interception into your projects.

At least in the EU prevention figures prominently in the call texts. But more importantly there is more and more interest in early disease.

Aligning with such trends puts your projects in the perfect position to leverage the work of others and such synergies needed to achieve major transformational changes.

Do you want to create projects that stand out?

At BioSci Consulting we are building concepts like interception into the projects we design.

The projects that stand out are those that incorporate state of art methods and technology and state of the art concepts.

With the existence of funding schemes like the Marie Curie doctoral networks which are bottom up call topics you do not need to wait for the right call topic to build a consortium.

If you think the time is right for you to build a consortium project reach out. I would be happy to help you explore the possibilities.

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1. Narchi, Jonas, and Eva C. Winkler. "Nipping Diseases in the Bud? Ethical and Social Considerations of the Concept of ‘Disease Interception’." Public Health Ethics 14.1 (2021): 100-108.

1. Siderowf, Andrew, et al. "Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study." The Lancet Neurology 22.5 (2023): 407-417.