Just nine months ago, we announced a milestone-based, research collaboration with AcuraStem to test thousands of compounds aimed at producing effective treatments for CMT2A. We are very pleased to report that AcuraStem has completed phase one of the CMT2A project and the results were greater than we expected.

To recap, the sub-aims of this first milestone were:

  • Create a neuronal cell line derived from a patient with CMT2A
  • Test the neurons for characteristics of CMT2A, including survival deficit
  • Show that the cell line demonstrates improved survival when exposed to neurotrophic factors (NTF), an agent known to support nerve cells

Not only were all three sub-aims met, but also a promising discovery was made during the course of the work. As part of the effort related to the survival aim, a compound (AS-1), under development by AcuraStem, was administered to the cells to test for possible effects on CMT2A motor neuron survivability. Interestingly, exposure to AS-1 in these screens showed improved cell survival. Based on these encouraging results, AS-1 has been identified as a promising new, preclinical drug candidate.

The next step in this project is to screen all U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved drugs to ascertain if any of these existing therapeutics generate more promising results than AS-1. The project’s use of AcuraStem’s iNeuroRx ® platform will accelerate the pace of drug screening and find drug candidates that likely have a higher probability of success in the clinic because they were discovered using the patient’s own cells.

What are the possible long term outcomes of this work?

1. Identify a small molecule that positively modifies survival of motor neurons in patients with CMT2A and thus may potentially modify CMT2A disease progression.

2. Using FDA/ EMA-approved drugs, which have already undergone rigorous clinical trial testing and have a documented positive safety and tolerability profile, we could potentially shorten the time to regulatory approval of one of these drugs as an available treatment option for CMT. Although formulation or dosing of any of these drugs may need to be modified for CMT, the first hurdle to approval — safety — has already been crossed. These drugs potentially could be fast-tracked to the clinic, either alone or in combination.

3. Demonstrate that the use of patient-derived cells improves the chances of successful translation of an experimental drug from cell to mouse to human. The hope is that patient-derived cells will manifest signs of CMT pathology in a petri dish. Currently, this “disease in a dish” method is being validated using cell lines for other forms of CMT. Our work is instrumental in setting the standard for development of different cell types which will allow for better understanding of the complex clinical and genetic diversity of CMT neuropathy, accelerate the path to a suitable high-throughput screening test, and expediting the process of bringing CMT drugs to market.

Additional Value Added Result of the Project

AcuraStem was originally focused on ALS as its primary indication before our collaboration. Because of our investment in this endeavor and the exciting preliminary results revealed in the completion of Aim 1, AcuraStem is considering adding CMT to its portfolio as a second lead indication. This means that as AcuraStem raises outside support, a portion of future efforts might be dedicated to additional CMT research.

Thus, our financial support already has the potential to produce value beyond the completion of our original aims, and could create a rising tide for additional CMT research investment.