In most circ*mstances, the word ‘progression’ is something positive, associated with moving forward or developing towards a better state. Progress has many meanings in social or political terms, but in common discourse, it is usually seen as a good thing.
However, in medical terms a ‘progressive disease’ is one that worsens over time. “You have progressed” is not something you want to tell your patients, or that you want to hear as someone living with a disease.
In my current role at Roche, as well as my time as a practising neurologist, I’ve worked closely with patients with – and in clinical research across – a number of progressive, neurological conditions, such as multiple sclerosis (MS), Alzheimer’s disease (AD), Huntington’s disease and spinal muscular atrophy (SMA).
These are all disorders that are characterised by a decline of motor and/or cognitive function caused by loss of neurons within the central nervous system (CNS). In these circ*mstances, progression may mean losing the ability to walk independently, or to use your hands to do daily tasks; it may mean that you are no longer able to recognise people, or that you have reached a highly debilitating, terminal stage of your disease.
The CNS has a limited capacity to maintain its function by remodeling itself to compensate for loss of nerve cells, fibres and myelin – known as its neurological reserve. Symptoms only start to manifest once the neurological reserve has been exhausted, the timing of which differs for every individual. Critically, nerve cells have very limited ability to regenerate in adulthood, which means that loss of neurological function tends to be permanent.
What is often overlooked is the fact that progression is typically present from the beginning of the disease, often long before a person is diagnosed. This progression may be gradual and not always easily noticed. This is what is now being called ‘silent progression’, because it evades notice. For diseases like MS, AD, HD or SMA, it is now understood that this progression may actually be the biggest factor impacting long-term outcome and quality of life.
Depending on the neurological disease, many people may not be diagnosed until they experience noticeable symptoms, resulting in progression potentially going unnoticed for months and even years. For those without noticeable symptoms or worsening disability, progression can be difficult to identify as imaging measures of progression are not established or standardised. Our challenges are that the ‘tools’ we physicians use to examine patients are often insensitive, new technologies can detect changes but can be hard to interpret, and we haven’t found a good way to really value the insights that patients have about their own disease.
So what does this mean for patients?
Neurological diseases are complicated. People with the same condition can experience different symptoms and course of disease, even though the underlying pathology is the same. This makes it even harder to understand the potential importance of symptoms and progression, or notice small increases in their impact that are accumulating slowly over time.
I believe that to make real progress in developing important medicines, this is a problem we need to solve, together and soon. It’s essential that we explore new possibilities in identifying progression early to effectively manage the underlying disabling course of neurological diseases – and that’s something that I’m proud to be part of championing in my work at Roche.
For example, in AD, we are developing new diagnostic approaches focused on blood-based neurodegenerative biomarkers and have created a cerebrospinal fluid assay platform that measures beta-amyloid and tau protein disease biomarkers to help detect disease at earlier stages. We’ve also developed PET imaging ligands to detect tau protein pathology in the brain. And our ongoing research in MS to identify biomarkers for nerve injury and immune-system activation may help measure new disease activity and make treatments more impactful.
These advancements will be at the core of a new model of care partnership between physicians and patients, based on transparency and ownership of data that will enable better decision making and optimised disease outcomes.
So what does this mean for us as clinicians?
As clinicians, it’s important for us to take an active role in helping our patients truly understand what disease progression means when it comes to their health. As well as help them also understand that while progression may not present itself in the same way in each person, it’s something that can be managed and should be treated as early as possible.
Furthermore, early treatment with a therapy that impacts progression is important to preserve patient function and ensure the highest-possible quality of life for those living with neurological conditions. If we’re able to recognise disease earlier, we can monitor patients more accurately and objectively, and more importantly, provide best-in-class treatment that is personalised for each and every patient, no matter their disease or level of progression. And that can make all the difference in making sure every patient achieves the best possible outcome.
This all is very relevant with the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2019 Annual Meeting taking place this week in Stockholm, Sweden. New data will be presented from leading experts that will hopefully help us in better understanding underlying disease pathology, and ultimately, introduce new therapies to help treat a range of neurological conditions.
With disease progression top of mind for me, what are you looking forward to seeing discussed most or being presented at this year’s meeting?
