What is Pharmaco-TMS?
Transcranial Magnetic Stimulation (TMS) is a non-invasive method using magnetic fields to stimulate brain nerve cells. In clinical trials, it measures cortical excitability as biological markers to study drug effects. (TMS and Drugs, Zeimann, 2004)
TMS-Electro Diagnostic Markers (TMS-EDMs) aid in exploring CNS therapeutics by providing:
- In-vivo markers for pharmacological activity
- In-vivo markers for biological processes
TMS-EDMs offer a better signal-to-noise ratio than EEG and don’t require specific tasks from subjects.
Observing TMS-EDMs before and after drug administration helps develop markers for cortical inhibition and excitation, valuable in early-phase trials for new drugs.
TMS is a reliable, non-invasive, and cost-effective method for identifying pharmacodynamic endpoints and neurophysiological correlates. It is useful for treatments and therapies for conditions like Epilepsy, ALS, Parkinson’s, MS, Autism, and Schizophrenia.
These neuro biomarkers are crucial for clinical trial strategies, but their integration needs careful coordination among stakeholders.
What we offer
State of the art TMS systems
TMS data processing and quality control
Tried and tested standard TMS protocols and procedures
Experienced and trained technicians
TMS-EEG
Electroencephalography (EEG) sensors are applied over the subject’s head and TMS is delivered over the EEG. The main parameters are the TMS evoked potentials (TEPs). TEPs are a reliable and reproducible alternating sequence of positive (P) and negative (N) peaks at a 25 (P25), 45 (N45), 100 (N100) and 180 (P180) milliseconds after stimulation.
Measurement of TEP amplitude allows a direct investigation of cortical excitability and connectivity in a highly time-resolved manner.
TMS-EMG
Electromyography (EMG) is applied at the contralateral hand muscle with TMS delivered over the cortex. The main parameter for single pulse TMS-EMG is the resting motor threshold (RMT) which reflects cortico-spinal excitability. RMT is the minimum stimulation intensity required to elicit a small motor evoked potential (MEP).
Paired Pulse TME-EMG protocols consist of a conditioning stimulus which precedes a test stimulus. The key parameters here are the inter stimulus intervals (ISI).
Advantages for Phase I clinical trials
There are several advantages to including TMS measures into a Phase I clinical trial:
- Objective measures of brain activity or neural excitability in response to a drug.
- Provides further understanding and confirmation of the drug’s mechanism of action.
- Contributes to understanding of the PK/PD relationship.
- Obtain non-invasive neuro biomarkers.
- Can provide early indicators of efficacy.
Clinical research services
Protocol design
We understand that effective protocol design is crucial for obtaining valuable insights into drug effects, thereby de-risking and guiding future pipeline decisions. Our neuroscience research consultants, with decades of combined experience, specialise in designing and developing scientifically rigorous protocols for transcranial magnetic stimulation (TMS).Integrated solutions
From combining TMS with EEG or with EMG, we offer a comprehensive range of integrated, non-invasive solutions to stimulate and image specific brain regions, which are crucial for objectively understanding neural pathways and exploring therapeutic interventions.Resourcing for data acquisition
Adhering to standard operating procedures and good clinical practice, we deploy highly trained and experienced neuroscience researchers and technicians to every clinical trial. Each team member is thoroughly trained on the specific technology solutions and the study’s data acquisition protocol. At the heart of this training is a commitment to consistently high-quality TMS data acquisition.Data analysis and interpretation
Analysing and interpreting neuroscience data requires a deep understanding of complex neural systems and the techniques and technology used to capture this information. Our neuroscience research consultants, with backgrounds in clinical and scientific research, are highly skilled in developing and utilising specialised analysis pipelines for both single and multi-modal neuroscience data.Technical support
With over 15 years of hands-on experience in designing integrated non-invasive brain stimulation and imaging solutions for scientific research, our technical support specialists offer expertise in crafting technical solutions for each clinical trial. Once the trial begins, they are readily available to provide ongoing technical assistance, ensuring smooth operations with a focus on consistency and high-quality data acquisition.Bespoke services
Our team will collaborate with you to identify and select the appropriate tests and measures based on your drug candidate’s mechanism of action, data from preclinical studies, and relevant academic and scientific literature. This approach allows us to create a tailored solution that provides meaningful and objective endpoints while seamlessly integrating with other clinical trial measurements. If you’re interested in incorporating any of these services and would like to discuss further, please get in contact!Frequently asked questions
TMS can reliably and reproducibly measure cortical and cortico-spinal excitability markers. These pharmacodynamic endpoints help demonstrate the drug’s neurophysiological effects, aiding in understanding its mechanism of action, PK/PD relationship, and providing early indicators of efficacy. This is especially useful for conditions like Epilepsy, ALS, Parkinson’s Disease, Multiple Sclerosis, Autism, and Schizophrenia.
TMS-EEG involves applying EEG sensors on the subject’s head and delivering TMS to measure TMS-evoked potentials (TEPs). TEPs, characterised by specific positive and negative peaks after stimulation, allow direct investigation of cortical excitability and connectivity in a highly time-resolved manner.
TMS-EMG involves applying electromyography to a muscle, typically in the contralateral hand, and delivering TMS over the cortex. The main parameter measured is the resting motor threshold (RMT), which reflects cortico-spinal excitability. Paired-pulse TMS-EMG protocols, involving a conditioning stimulus followed by a test stimulus, help investigate neurotransmitter effects and cortical inhibition/excitation.
To incorporate Pharmaco-TMS into your clinical trial, please contact us. Our team of experts will assist you in designing and implementing TMS protocols tailored to your study’s needs, ensuring precise and reliable assessment of cortical activity.