ALS Association Meeting Presents Data on Research Achievements at Recent AAN Meeting

The Annual Drug Company Working Group and the American Academy of Neurology (AAN) meetings were recently held by the ALS Association last month in Washington, D.C. with main focus on amyotrophic lateral sclerosis (ALS). The association is now sharing the most important data presented at the meetings on new treatments, delivery methods, and clinical trials for the disease.

There is currently no cure for the neurodegenerative disease and the treatments available are not able to substantially extend the lives of patients, whose brain and spinal cord nerve cells are affected. ALS patients lose their capacity to control the movement of the muscles, which can cause total paralysis and death. “This meeting is an important opportunity for those working in ALS drug development, and those who are interested in getting into the field, to learn about progress and share new approaches,” explained the chief scientist for the ALS Association, Lucie Bruijn, PhD, MBA.

At the meeting, Harvard University researcher Kevin Eggan, PhD presented data on a new drug discovery tool based on induced pluripotent stem cells (iPS cells), which was used to design an upcoming clinical trial for the evaluation of a novel ALS drug effectiveness. The drug Retigabine was already approved by the FDA to treat epilepsy and is able to decrease neuronal firing in order to calm down the nerve cells and prevent damages from over-excitation.

The investigator is planning to initiate a clinical trial at 12 clinical centers included in the ALS Association-funded network, Northeast ALS Consortium (NEALS). Recently, over-excitement of the motor neurons in ALS patients has been reason for attention in the research community, and Eggan aims to study the influence of a non-invasive procedure called transcranial electromagnetic stimulation, which chemically transforms skin cells into stem cells and treats them to become motor neurons.

If the placebo controlled study reveals successful outcomes, which means a decrease in the excitation provoked by the drugs, the investigators plan on initiating a longer-term trial to evaluate its capacity to slow the disease. The iPS cell lines will be used to better understand the phenomenon of over-excitability of the motor neurons, in particular the ones in the brain and spinal cord, the “upper” motor neurons.

The developments accomplished by Lauren Sciences regarding a novel drug delivery system were presented by its founder and CEO, Susan Rosenbaum. Despite the benefits of certain drugs, they may not be able to transpose the barrier created by blood in the brain, reducing the drug delivery to the central nervous system and consequently its effects. The new biologically based system shuttles encapsulated drugs through the blood-brain barrier, enabling its peripheral administration.

The company is currently working on the lipid-based spherical vesicle system to enclose the glial-derived neurotrophic factor (GDNF) drug within it and treat ALS. GDNF has been proven effective in increasing motor neurons’ survival, and the system is expected to deliver certain portions of medication in customized cell targets. “The vesicles cross the blood-brain barrier without disrupting it,” explained Rosenbaum. “Ultimately we hope to translate these into clinical studies.”

Another company that presented its ALS achievements was Cytokinetics, which presented updated data from its tirasemtiv clinical trials. The company’s chief medical officer, Andrew Wolff, MD, presented the results of the study that demonstrated the drug’s effectiveness in improving muscle output at mid-levels of exertion, by restoring part of the lost strength, even temporarily. Despite the fact that the primary endpoint of the BENEFIT trial was not met, altering the ALS Functional Rating Scale score due to tirasemtiv, the study revealed improvements in the slow vital capacity, an important respiratory measure.

“We believe this is a clinically meaningful effect that warrants further study,” stated Wolff, announcing the company’s plans to initiate a larger phase 3 trial. The new study will take into account the lessons learned from BENEFIT, and the company now aims to improve early dizziness compensation and increase dosage at a slower pace in order to decrease the risk of the common side effects and increase drug tolerability. There is still no information on the patient enrollment for the double-blind study, which will last 48 weeks and is scheduled for the second quarter of the year.

In addition, the ALS Association also presented its initiative to create a “guidance document” particularly focused on ALS to submit to the FDA. The association aims to gather patients, caregivers, advocacy groups, researchers and the industry in order to develop a consensual work with several different views and fields of expertise. The final result is meant to comprise guidance on the ideal approach of the FDA to ALS treatment, focused on accelerating research, improve industry clarity and deliver effective therapies.

The ALS Association is now working similarly to previous work done on ALS by the Muscular Dystrophy Association (MDA) and plans to invite representatives from both the FDA and the National Institutes of Health (NIH) to join the project for the first patient focused guidance initiative for ALS drug development, as well as the ALS community. The association believes that the final document will be ready to be filled to the FDA by the first quarter of next year.

“This groundbreaking effort should lead to faster trials, accelerate drug development and bring new treatments from the lab to patients as soon as possible” added Bruijn. “We are working with the entire ALS community, including other ALS organizations, industry, academia, government, and most importantly patients and caregivers. We are confident this effort will make a significant difference in the fight to find a treatment for ALS.”