July 30, 2024

You or your loved one is sitting with a life changing diagnosis – a genetic, terminal disease.  All at once, time grinds to a halt and simultaneously goes into overdrive, rushing by so fast you can hardly get a grasp.  Emotions spiral.  Questions explode in your brain.  Decisions come in rapid fire.

One of those decisions may be, “Do you want to participate in research?”  Even this question brings more questions that must be sorted through and answered.  Is it an observational study?  Is it an interventional study?  What’s the difference?  Will I have to travel?  Can I travel?  What will participation cost?  How will this research benefit me?  How will it benefit my family?  How will it benefit others? 

Today, I want to talk about a very important observational study that, if offered for your particular disease, will benefit current and future research and therapy development.  First, let’s review the difference between “observational” and “interventional” studies.  Observational research, as the name indicates, is ONLY observation based.  There is no drug or therapy offered.  It is an opportunity for researchers to observe the disease as a whole or specific aspects of the disease that research has indicated may be important.  Interventional research is a study where a drug or therapy is given to see what effect said drug or therapy has on the progression of a specific disease.

Natural History Studies are a common type of observational study.  Simply, a natural history study observes the natural progression of a disease.  So, why is this important and how does this benefit drug development?

The most obvious benefit of a natural history study is that it helps doctors and researchers better understand the disease – first indicators of the disease, stages of disease, and biomarkers are just a few factors that are identified and monitored during a natural history study.  In ALSP, for as much as we do know, there are still large gaps in disease understanding.  A natural history study is one way in which that understanding is increased, and doctors and researchers will use that understanding to more accurately diagnose the disease, treat symptoms, and create therapies.

Having a comprehensive understanding of disease progression is also necessary for appropriate clinical trial design.  A natural history study can provide insight when determining how long a clinical trial needs to be and what end points or outcome measures are most important to evaluate.

Pharmaceutical companies work closely with regulatory agencies.  In the US that is the FDA.  When running a clinical trial on a particular drug or therapy, pharma and the FDA are trying to answer two important questions.  One: is the drug/therapy safe?  Two: is the drug/therapy effective at treating the disease?  In disease groups that are larger, clinical trials have two groups.  One group receives the intervention (drug/therapy).  The other group received a placebo.  The clinical trial runs for a specific time limit that is determined by pharma and the FDA.  Once the trial is concluded, data from each group is gathered and compared.  They use the data to determine answers to the above questions – is the intervention safe and is it effective?

When working to create therapies for rare diseases, natural history studies are often used as the control arm, or placebo arm, in clinical trials.  Because rare disease groups are small, there often are not enough patients to have two groups – the interventional group and the placebo group.  Natural history studies can be utilized to overcome this potential problem.

Putting it into real context – this is the method that Vigil Neuroscience is hoping to use as they work toward drug approval.  The clinical trial is currently fully enrolled.  Everyone participating in the trial is receiving the therapy.  No placebo is being given to any participants.

Vigil Neuroscience is also running a natural history study to better understand the natural progression of the disease and to provide data for the control arm of the clinical trial.  When the clinical trial is complete – meaning every participant has received all doses and had final scans and clinical assessments – all the data gathered during the duration of the trial will be gathered and analyzed.  Vigil Neuroscience will also be gathering and analyzing the data obtained in the natural history study.  The natural history study data will show the natural progression of ALSP when no therapy is used to slow the devastating effects of the disease.  The clinical trial data, when compared to the natural history data, will show what effect the drug intervention had on the progression of the disease.  Hopefully when comparing these two data sets, the answers to those two important questions – is it safe and is it effective – will be clearly answered.  

Sisters’ Hope Foundation hosted an informative webinar “Biomarkers 101.”  In this webinar, Dr. Petra Kaufmann, Chief Medical Officer at Vigil Neuroscience, gives a fantastic overview of the importance of natural history studies and how they are used to track biomarkers.  You can find that here: Webinars – Sisters’ Hope Foundation (sistershopefoundation.org)

The natural history study is still accepting new registrations.  Please find more information here: Study Details | Natural History Study in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia | ClinicalTrials.gov