Drug development is a complicated, expensive, and time-consuming activity that requires thoughtful application of scientific and medical principles to bring the best possible treatments forward to affected patients. In general terms, to improve our ability to quickly advance potential treatments through the early phases of clinical evaluation, we need to improve how we measure drug responses to ensure we have high confidence in drug effect and in drug safety. To the extent possible, it is important to limit misleading placebo responses in human disease trials, where participation in a study may falsely lead to patients ‘feeling better’ and creating misinterpretation of real drug effects. Eliminating misleading placebo effects will enable smaller, more rapid Phase II trial designs that will significantly reduce the time needed to make definitive decisions on whether to move to much larger and critical Phase III trials.

To limit placebo responses and improve drug signal detection in brain disease indications, Spinogenix is focusing on two areas: 1) using direct measures of neurophysiologic activity that will remove any bias, and 2) utilizing performance-based measures, to directly measure what a person physically or mentally can or cannot do when treated and relating this directly to treatment effects.

Studying brain neurophysiologic activity with EEG is a feasible and accurate way to evaluate whether a drug is having a positive, or negative, impact on brain function. Many brain/central nervous system disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, schizophrenia, and neurodevelopmental disorders show patterns of abnormal EEG activity, both when the brain is at rest and when the brain is exposed to stimuli (like listening to certain patterns of sounds). EEG is a very reproducible measure and reliable measurement, so that if EEG change happen with drug treatment, we can be assured the change is likely drug-associated. Taking this approach in human clinical trials, in our academic research at Cincinnati Children’s Hospital we have been able to detect drug-associated treatment changes with small numbers of patients, down to even just 4-6 patients receiving an active new drug under study.

Transcranial magnetic stimulation (TMS) is another way to test and evaluate brain function in clinical trials. TMS, which exposes the brain to pulses of magnetic energy, can be used to assess brain adaptability. TMS can be used to quantitatively measure deficits in brain function, and then to evaluate if such deficits improve with drug treatment. Like EEG, TMS measurement is very consistent. This enables TMS to detect potential drug-associated treatment changes with small numbers of patients in Phase II trials. Taken together, we believe the use of both EEG and TMS in our clinical studies will help Spinogenix move our drug candidate most efficiently toward broadly treating patients suffering from ALS and other diseases as mentioned above.

Outside of using technologies like EEG and TMS to detect brain activity changes, we can also reliably measure an individual’s functional performance when receiving novel drug treatments. Examples include collecting respiratory volumes and respiratory effort in ALS patients to gather precise, reproducible measures that are conducive to inclusion in drug trials. Motor strength and other physical performance measures can also be reliably monitored in trial settings. In developmental disorders, as well as in patients with ALS, schizophrenia, and dementia, memory and learning are often impaired, and these cognitive deficits can also be reliably measured with performance-based tests. This work includes the use of computer-based cognitive testing that can be reliably administrated in various settings and well-synchronized across clinical trial sites.

Spinogenix is committed to the concept of using highly reliable and quantitative brain activity measurements and human performance-based outcomes in their clinical trial designs. So far, the Spinogenix drug candidate has demonstrated the ability to enhance brain synapse connections across many preclinical models. If similar results occur in humans, as we hope they will, these changes will be detected using EEG and TMS to document favorable brain activity changes, and the performance-based measures described will further confirm beneficial function as changes as a result of treatment. Taking these steps will enable Spinogenix to quickly detect potential changes with treatment and enable rapid expansion to much larger clinical trials in a range of brain diseases.

About Spinogenix 
Spinogenix was founded with the mission to develop transformative therapeutics for diseases involving synaptic loss and dysfunction. Our drugs are designed to regenerate synapses to reverse declines in cognitive and motor function and fundamentally change treatment paradigms by restoring neuronal connections regardless of the underlying cause of synapse loss. Synapse loss is associated with a variety of neurological and psychiatric diseases, such as ALS, Alzheimer’s disease, Parkinson’s disease, and schizophrenia. More information on Spinogenix can be found at www.spinogenix.com.