After a clinical study showed the NeuroMotor Pen can be used to distinguish Parkinson’s Disease (PD) from other movement disorders, with an accuracy of 80% and sensitivity of 95%, Med-Tech Innovation News caught up with Manus Neurodynamica CEO Dr Rutger Zietsma, to find out its implications.
Can you summarise what the recent clinical studies have shown with the NeuroMotor Pen (NMP)?
Parkinson’s diagnostic clinical outcome validation
A series of bench testing and clinical validation studies have taken place since 2011 in Europe with opinion leaders in the field of Movement Disorders in Amsterdam, Groningen, Dublin and Newcastle-upon-Tyne, demonstrating that there are specific biomarkers for the disease processes in PD that NMP is uniquely able to capture.
The latest study completed in 2020 resulted in diagnostic accuracy of NMP (PD vs other movement disorders) of 80% (sensitivity of 95%; specificity of 63%) in 132 undiagnosed patients in movement disorders clinics with tremor and other movement symptoms, for whom it was difficult to make an unequivocal diagnostic decision and the consultant neurologist ordered a DatSCAN for confirmation. NMP was compared to current best practices (specialist conclusion six months after the first appointment, based on as a minimum DaTSCAN outcomes as well as MDS-UPDRS scores).
It was concluded that the diagnostic accuracy of NMP (PD vs other movement disorders) is 80% with a sensitivity of 95% and a specificity of 63%.
For information: Prior studies were published in peer reviewed journals and reported the following:
- Standardised NMP drawing tasks suitable for quantification of motor skill and PD symptoms with NMP biomarkers;
- Accurate quantification of motor skill and response to dopaminergic medication with NMP biomarkers. Accuracy and resolution were higher than reference measures, including Purdue pegboard task and standard clinical assessment scores like the UPDRS-III rating scale. NMP quantified the presence of tremor and minute variations, which clinical specialists were not able to detect with the naked eye.
- High reproducibility of motor biomarkers.
- Validation on 92 patients with an established diagnosis (which is a much easier diagnostic scenario than looking at undiagnosed patients – reported above with an accuracy of 80%) resulted in classification accuracies of 82% for essential tremor, 69.8% for functional tremor and 72.2% for enhanced physiological tremor.
Schizophrenia
The utility of the NMP in the assessment of the extrapyramidal adverse effects of antipsychotic drugs was validated in collaboration with The University of Edinburgh and Lothian Health Board. Twenty-one patients living with psychosis agreed to participate, gave informed consent, and were assessed by the current standard clinician-rated measure, the Extrapyramidal Symptom Rating Scale (ESRS), which assesses four types of drug-induced movement disorders: parkinsonism, akathisia, dystonia, and tardive dyskinesia, as well as by a standardised battery of writing tests using the Manus NeuroMotor Pen (NMP).
The results showed that the device was highly usable and acceptable to patients living with psychosis, and features measured by NMP were highly predictive of the clinical examination findings determined by ESRS. In addition, tremor, bradykinesia and facial features of drug-induced antipsychotic adverse effects were also predicted by features measured by NMP.
The investigators concluded that the study suggests that the NMP is the first easily portable device capable of making an objective evaluation of the extrapyramidal adverse effects of antipsychotic treatment and suggest that the NMP has clinical utility and validity to guide the treatment and management of those taking antipsychotics.
NMP offers an application in monitoring how effective drugs are and more importantly also in finding the right dose to give patients the optimum dose that provides all benefits but avoids the side effects. These side effects are a disaster that always creates other clinical problems - often resulting in loss of writing ability (and losing job). Psychiatrists have known this for 40 years and pharma companies have brushed it under the carpet until now. The market is now opening up with pharma looking for solutions. I am talking to both a pharma company and two new academics about trialling this important application on a larger scale.
You’ve spoken to us previously about the NeuroMotor Pen being used to treat Parkinson’s, did you always envisage it could be used for other conditions?
Yes, absolutely. Our initial focus has been on Parkinson’s diagnosis and monitoring as an important area for which there were strong indications that a solution could be developed that is sufficiently accurate. It was essential to have an initial focus area for R&D along with a commercial strategy in order to focus resources to deliver a marketable product. I always envisioned diversifying once the PD market, as our first beachhead, had gained sufficient traction.
Nevertheless, there are many neurological disorders that affects the extrapyramidal system, which is the part of the nervous system involved with fine tuning voluntary movement and therefore lead to movement abnormalities. All of these diseases could potentially benefit from non-invasive assessment of these ‘extrapyramidal effects’ to support early identification, differential diagnosis and treatment. Other disease areas are multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), but also Attention deficit hyperactivity disorder (ADHD) etc.
One example where we are already diversifying and have obtained data is the NMP use in schizophrenia, which has many parallels with PD. NMP enables the healthcare professional to accurately and objectively quantify scores normally (subjectively) observed by the clinician. Any patient on antipsychotics is normally assessed six times per year and the automated digital record keeping is a huge benefit as psychiatrists are not very good at keeping records - even if they are good at observing/quantifying the movement problems.
Did you imagine that would use it as a diagnostic tool for neurological conditions?
Yes, this was the intention and the first investment along with a grant was specifically for development of the Parkinson’s diagnostic application.
Can you summarise the conditions that the neuromotor pen can now be used for?
We currently have a regulatory claim for Parkinson’s (PD) diagnosis only and we offer it as a PD diagnostic. We do not market NMP for any other use yet.
Nevertheless, the PD regulator claim for diagnostic means that NMP is not only able to confirm PD, but also able to differentiate between different movement disorders that mimic the PD symptoms, such as essential tremor (ET), MS, PSP, MSA, psychogenic tremor etc, so the actual application is broader. In practice, NMP will help clinicians not only to diagnose PD, but also pinpoint what diseases the patients may or may not suffer from, based on the test results.
We are also able to offer NMP as an ‘off label’ solution in other areas of application, such as PD monitoring or EPS assessment in schizophrenia etc (basically any use an academic clinician can think off).
In light of these results, what next for Manus Neurodynamica?
- Increased sales and marketing activities for the PD beach head market.
- We expect to have at least 5 reference centres in the UK within 12 months’ time.
- Obtaining FDA approval in the US.
- Progressing trials with at least one pharma company on a commercial basis (discussions on-going)
- In parallel, we are developing the Alzheimer’s and schizophrenia solutions.
