MyTrail: Precision Medicine Clinical Trials for Movement Disorders at BWH
APPROACH IN THE CLINIC: We aim to develop different approaches to clinical trials. We select certain patients for “deep phenotyping” – a program we call “MyTrail” – in which we follow their trajectory with clinical measurements, biometrics and biomarkers in the blood, spinal fluid and with brain imaging. With our collaborators in the Brigham and Women’s Movement Disorders Genetics Clinic, we obtain a whole-genome sequence. A skin biopsy enables us to develop a personalized stem-cell model from each patient.
PERSONALIZED STEM-CELL MODELS: From skin biopsies we, firstly, generate an induced pluripotent stem cell from the patient. This cell is an embryonic stem cell-like cell that enables us to generate neurons and other CNS cell types from our patients. Secondly, from skin (or spinal fluid or even a nasal brushing) we capture the toxic protein (alpha-synuclein, for example) that is aggregating in that specific patient. This allows us to create a truly personalized model from the patient – capturing the right cell type and the right form of the aggregating protein “in the dish” in our lab.
“n-of-few” CLINICAL TRIAL APPROACH: Ultimately our approach culminates in the introduction of a drug at the right time. For patients we actively track in the clinic, we will have the prior clinical and biomarker “history” of the patient, enabling us to better understand the response to that drug. Testing the drug in a patient’s own brain cells in the lab before a clinical trial is attempted should increase our chances of success in the clinic.
GENE THERAPY: Gene therapies: We are working with collaborators to better understand gene knockdown approaches (e.g. antisense oligonucleotides). We “de-risk” these therapies in stem-cell models matched to patients. The aim is to better understand a therapy before it is introduced into the patient.