The ReCognitION Study
An alternative path towards new treatment options
Most of the ongoing research about Myotonic Dystrophy is based on sophisticated approaches dedicated to fix the genetic abnormality at the origin of the disease. These scientific investigations can be promising, but the roadway is long before achieving a systemic drug formulation.
In contrast, ReCognitION is a follow-up study of the European OPTIMISTIC clinical trial with a novel approach for the identification of novel treatment options based on drug repurposing. OPTIMISTIC, the largest European trial in Myotonic Dystrophy type 1 (DM1) to date, took place between 2014 and 2017 in four countries: The Netherlands, France, U.K. and Germany.
A cohort of 255 patients was recruited to evaluate the effect of Cognitive Behavioural Therapy (CBT), combined with physical training, on the quality of life of DM1 patients. Additionally, thorough clinical characterization of the enrolled patients was performed, and human samples were collected during the clinical interventions.
CBT is a form of healthcare based on the concept that patients thoughts, feelings, physical sensations and actions are interconnected. Negative thoughts, feelings and behavior can trap them in a vicious cycle.
In an adaptive way, the therapist proposes practical solutions to improve the state of mind and promote healthy behavior. Unlike some other therapies, CBT deals with the current condition rather than focusing on issues from the past.
In OPTIMISTIC, the cohort was divided in two groups, the first received CBT, the second continued usual care. CBT consisted of up to 14 sessions with a psychologist during a 10 months period. The sessions focused on problems and symptoms of DM1 patients, such as reduced activity, stress, anxiety, fatigue, reduced initiative, social interaction, sleep quality and pain. Additional Physical training consisted of aerobic exercise, under the control of a physiotherapist. All patients completed measurements of activity performance (walking distance, muscle condition).
Summary: For most of the patients, OPTIMISTIC demonstrated a visible and measurable beneficial effect in evaluated domains: social participation, exercise capacity (walk test), fatigue, objective physical activity and muscle condition. All positive effects were maintained at a follow up assessment.
A subgroup of non-responder patients was also identified. This allowed us to study the question of why some patients improved while others did not. This is where ReCognitION comes in.
The central hypothesis of ReCognitION is that pathways associated with positive response to CBT can be consolidated or reinforced by conventional drug therapies that target the same biological pathways.
This study is a pre-clinical study, taking advantage of all information and material collected from OPTIMISTIC. No additional clinical investigation is required. The following activities will be covered:
- Provide a detailed analysis of positive responses to the CBT behavioural intervention in the OPTIMISTIC responding group.
- Identify the molecular signature of the response by means of bioinformatic approaches.
- Identify drugs which target the same pathways, prioritizing drugs which are already approved for clinical use (drug repurposing).
- Measure the effect of these drugs on the molecular profiles of DM1 patient cells and the behavioural phenotypes of DM1 mouse models.
Summary: At the end of the project, the selected drug-candidates will be tested in animal models and human cells. Further investigations involving DM1 patients will be necessary before approval of the drug-candidates for clinical use. The safety and tolerability studies could be accelerated if the expected dose for DM1 stays within the limits of the drug certification for its original pathology, but a “random versus placebo” phase 3 study will be required to confirm the positive effects of the drug on patients.
The ReCognitION program is a precursor of innovative care techniques in many points.
At first, the cure is not based on a pre-established protocol validated for the disease in all patients at the same time, but built individually after a detailed analysis of the patient needs to improve his quality of life. This approach is promising for Myotonic Dystrophy whose variability of symptoms is well known, but could also be adapted to other neurological diseases.
Also, the drug repurposing strategy based on the reverse engineering of a positive response to a behavioural intervention may set the scene for future drug development trajectories in rare diseases.
Finally, the combination of care techniques given by different communities in order to maximize the effects is very innovative. For Myotonic Dystrophy Type 1, the psychologist together with the patient identifies in a shared decision making the patient needs and realizes the CBT intervention; additional physical training is performed by a physiotherapist or even a sport coach, and the drug delivery is controlled by a physician.
The diversity of actors converging towards the quality-of-life improvement of the patient is also an attractive way to obtain and maintain the commitment of patients sometimes affected by apathy and misestimation of themselves.
Somewhere, a new highly personalized medicine is emerging …