PLUS ALS
PLUS ALS is the name of an international collaboration between the ALS Centrum Netherlands (UMC Utrecht) en ALS Centre Leuven (UZ/KU Leuven) to accelerate ALS clinical research by using an international biomarker platform
PLUS ALS is the name of an international collaboration between the ALS Centrum Netherlands (UMC Utrecht) en ALS Centre Leuven (UZ/KU Leuven) to accelerate ALS clinical research.
PLUS ALS is launching a new biomarker platform that will allow researchers to determine earlier and more reliably whether new drugs are effective. Funded by the Romo Foundation, this five-year project brings together the expertise of both ALS centers.
Why PLUS ALS?
In recent years, our knowledge of ALS has grown significantly. Thanks to new laboratory techniques, disease processes can be increasingly well-measured using so-called biomarkers, such as proteins in the blood or neuroimaging techniques like MRI, to visualize the activity and progression of the disease.
However, most of these measurement methods have barely been tested in people with ALS. PLUS ALS aims to change this: for the first time, multiple biomarkers will be studied simultaneously and over time within the same group of ALS patients. This approach will make it possible to quickly determine which measurement methods are most suitable and which new drugs have the highest chance of success.
Collaboration and expertise
The project builds on a long-standing collaboration between the two national reference centers for ALS. Both centers contribute complementary expertise to the initiative.
The project is supported by the Dutch ALS Foundation, ALS Liga Belgie en de Dutch ALS patient association and uses the international research initiative TRICALS.
The people behind PLUS ALS
Frequently asked question about PLUS ALS
What is PLUS ALS?
PLUS ALS is a leading international collaboration between the Netherlands and Belgium in the field of drug and biomarker research within ALS. PLUS ALS aims to create a platform for testing new therapies faster in small-scale drug trials. We do this by developing new biomarkers* that allow us to better match the right patients to the right drug trial and to monitor them throughout the disease process. This allows us to measure more quickly whether a drug is effective, so that drug research into ALS can be accelerated.
*A biomarker (biological marker) is something in the body that can be measured and provides information about how the body works or whether someone has a disease.
Which parties are involved in PLUS ALS?
PLUS ALS is a collaboration between: ALS Center UMC Utrecht, UZ/KU Leuven, ALS Liga België, Stichting ALS Nederland and the ALS patiëntenvereniging (ALS patient association), funded by the Romo Foundation.
Which researchers are involved in PLUS ALS?
Leonard van den Berg (UMCU)
Philip van Damme (UZ/KU Leuven)
Ruben van Eijk (UMCU)
Ewout Groen (UMCU)
Joke de Vocht (UZ/KU Leuven)
How long does the PLUS ALS project run, and who funds it?
It is a five-year project, funded with 7 million euros by the Romo Foundation.
Who is the Romo Foundation?
The Romo Foundation is a family fund that focuses on promoting scientific research and development in the Netherlands and Belgium in the fields of oncology (with an emphasis on childhood cancer in Belgium) and neurodegenerative diseases (with an emphasis on ALS and Parkinson’s disease).
How relevant is PLUS ALS for people who are currently living with ALS?
PLUS ALS focuses on finding biomarkers that show rapid change over time. If these are found, they can also be used for people who currently have ALS. Another important part of PLUS ALS is conducting short drug trials that are monitored using biomarkers. People who currently have ALS may be able to take part in these trials if they are eligible.
What is a biomarker, and what exactly does a biomarker measure? Is it a confirmation that you have ALS, or that you might get ALS, or does it measure the progression of the disease?
A biomarker (biological marker) is something that can be measured in the body. It provides information about how the body works or about a disease.
A biomarker can, for example, be a substance in the blood or cerebrospinal fluid, such as a protein. It can also relate to how well the muscles or the brain are functioning. In addition, a biomarker can be a change visible on an MRI scan, for instance in the brain or spinal cord.
The US drug regulator (FDA) has classified biomarkers into seven groups. For PLUS ALS, two of these groups are the most important: prognostic biomarkers and pharmacodynamic biomarkers. A prognostic biomarker measures how a disease progresses. The goal of PLUS ALS is to find biomarkers that can measure changes in disease progression quickly and clearly. A pharmacodynamic biomarker shows how the body responds to a treatment, helping researchers better determine whether a treatment is working.
Why is biomarker research needed? Isn't the ALSFRS-R score already available to show whether a new treatment works? Wouldn't it be better to spend the money on drug research itself?
The biomarkers currently in use, such as the ALSFRS-R, can show how the disease develops and whether a drug is working. This usually requires large drug trials lasting twelve to eighteen months. These trials are expensive and often do not lead to a new drug.
With PLUS ALS, we want to better determine which drugs are promising enough to study in large trials. That’s why we first carry out short trials with small groups of patients. For this, new biomarkers are needed that can show changes within just a few weeks or months.
With these new biomarkers, we can assess more quickly whether a drug influences the course of the disease. PLUS ALS therefore focuses both on developing new biomarkers and on testing these biomarkers in small drug trials.
A lot is already happening in the field of biomarkers, what does PLUS ALS add to this?
A great deal of biomarker research for ALS is being conducted worldwide. However, these biomarkers are not yet always properly tested and used in drug research. PLUS ALS brings this together in a single program: we develop biomarkers, test whether they work well, and then use them in drug trials.
In addition, we work closely with researchers from other countries. We coordinate our research and share knowledge, which helps prevent the same research from being unnecessarily duplicated.
How do you decide what to focus on, and not focus on, within biomarker research?
We don’t rule out biomarkers that have already been studied by other researchers. There are often still questions that need further investigation.
An important strength of PLUS ALS is that the participating centers in the Netherlands and Leuven have been collecting patient data and body material for research for many years. This gives us access to a large amount of information, and the patient groups can be compared well with one another. This makes it possible to investigate precisely how biomarkers relate to disease progression, an opportunity many other research groups don’t have.
In addition, the PLUS ALS researchers collaborate with many researchers from other countries. This keeps us up to date on the latest developments and allows us to quickly apply new knowledge in our research.
If, after 5 years, we have some biomarkers, does the step toward a drug still need to follow? Does this mean UMC Utrecht and KU Leuven assume they won't find a drug in the next 5 years?
PLUS ALS is intended to determine which drugs should be studied further. Over the next five years, we will investigate multiple drugs. We look for indications that a drug can slow or change the disease in the short term. If the results of a trial are positive, the drug is then studied in a larger phase 3 trial. In this trial, researchers look at whether the drug works well and is safe for long-term use. Based on the results of this phase 3 trial, a decision can be made on whether the drug is suitable for treating ALS.
Is this research also relevant for patients with familial ALS?
It is important to speed up drug research. This can be done by using biomarkers that quickly show whether a treatment is working, which is important for everyone with ALS.
In the hereditary form of ALS, it is sometimes already known which change in the DNA causes the disease. This information can help researchers design the research more effectively, and can also help them better understand changes in biomarkers.
Can I, as a patient, do something to contribute to this project?
Patients can contribute in several ways. The most important way is by taking part in scientific research, such as these biomarker studies or, if eligible, drug trials.
In addition, involvement can also include:
- taking part in observational studies (for example, having blood drawn);
- sharing clinical data;
- contributing to patient panels or through lived experience.
The treating neurologist or the research team at UMCU and UZ Leuven can explain what options are available and whether participation would be suitable.
How is my privacy as a patient safeguarded with regard to the biomarkers in the database?
When you take part in research, we will explain in advance, in an information letter, what we use your data for. We will also ask your permission in advance to share your data with others.
To protect your privacy, your data and body material are assigned a code. Your name and other directly identifying information are left out. Only with the key to the code can data be traced back to you. This key is kept securely at UMC Utrecht. The data and body materials sent to any other parties involved contain only the code, not your name or other identifying information. Your data also cannot be traced back to you in reports and publications about the research.
As a Belgian patient, do I need to travel to Utrecht for, for example, an EMG?
No, in principle not. An important starting point of PLUS ALS is that measurements take place, as much as possible, in the patient’s own country and own treatment center. For Belgian patients, this means examinations can be carried out in Leuven, and for Dutch patients, in Utrecht.
This may only happen in special situations, for example when a certain type of measurement is only available at one location and a person wishes to take part in that part of the research. In that case, travel and other costs will be reimbursed.
Can every person with ALS participate, or are there inclusion criteria?
All people living with ALS can take part in the research into finding better biomarkers. Additional conditions may apply for small drug trials. These conditions are meant to reduce the risk of side effects, or to select participants who fit the goal of the trial, for example based on how far the disease has progressed or how quickly it is expected to develop.
What if I received my diagnosis, for example at UZ Gent, based on an EMG? Can this data be used for this project, or do I need to have another EMG done, this time in Leuven?
Whether we can use this data depends on how extensive the EMG examination was. The examination also needs to provide enough information to make a definitive ALS diagnosis. The neurologist or research assistant will discuss this with you during the intake for the study.
How do I stay up to date on news about this project?
When there are interesting developments, these are shared through the channels of the parties involved, for example through newsletters and social media.
Sign up for the ALS Centrum newsletter (in Dutch) to stay up to date on the latest developments.