Seelos Therapeutics received notice from the Food and Drug Administration (FDA) that the company may proceed with initiating a Phase IIb/III trial studying SLS-005 (trehalose) for the treatment of Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).

Mutations in the C9orf72, SOD1, FUS, and TARDBP genes can cause familial ALS and contribute to the development of sporadic ALS. These mutations contribute to the death of motor neurons and ALS affected motor neurons develop a buildup of protein aggregates such as TDP-43 and SOD1. In in-vivo studies of ALS, trehalose has been shown to increase clearance of TDP-43, decrease SOD1 and SQSM1/p62 aggregates and monomers, delay the progression of the disease, preserve ventral horn motor neurons and increase muscle fiber size.

"ALS is a debilitating disease which currently lacks a cure and there is significant evidence suggestive of trehalose having the potential to alter or slow the progression of ALS," said Raj Mehra Ph.D., Chairman and CEO of Seelos. "Receiving the FDA notice that we may begin a registrational Phase IIb/III study is a transformative event for Seelos and our hope is that SLS-005 can offer a potential option for patients. The FDA signoff to begin this pivotal study allows Seelos to focus on ALS as the lead indication for SLS-005. We remain committed to our work in additional indications as well."

"Several preclinical studies have demonstrated the potential of trehalose as a treatment for ALS, demonstrating preservation of motor neurons, motor function and prolonged survival. We are excited to start our clinical program for this devastating disease," said Warren W. Wasiewski, M.D., F.A.A.P., Chief Medical Officer of Seelos.

Seelos' Phase IIb/III trial plans to enroll 160 patients with either familial or sporadic ALS in a double-blind placebo-controlled trial. Patients will be randomized 3:1 (drug:placebo) and studied with a primary endpoint measuring change from baseline on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score at 24 weeks. Secondary endpoints will also be measured at 24 weeks, including change from baseline in slow vital capacity, muscle strength, quality of life measurements as well as additional signs of disease progression. 

Trehalose is a low molecular weight disaccharide (0.342 kDa) that crosses the blood brain barrier, stabilizes proteins and importantly, activates autophagy, which is the process that clears material from cells. In animal models of several diseases associated with abnormal cellular protein aggregation or storage of pathologic material, it has been shown to reduce aggregation of misfolded proteins and reduce accumulation of pathologic material. Trehalose activates autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. Activation of TFEB is an emerging therapeutic target for a number of diseases with pathologic accumulation of storage material. 

According to the National Institute of Neurological Disorders and Stroke, Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch (called fasciculations), and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. The majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. Although family members of people with sporadic ALS are at an increased risk for the disease, the overall risk is very low and most will not develop ALS.

Most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt, or reverse, the progression of the disease.