Seelos Therapeutics has recently received approval to proceed with phase IIb/III of their trial of trehalose, an investigational ALS treatment. The FDA alerted Seelos of this approval on August 7 after reviewing positive data from pre-clinical trials.
About Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS) is a progressive, neurological disease in which nerve cells in the brain stem, brain, and spinal cord deteriorate. Due to this deterioration, muscles weaken and people lose control of them and their voluntary movement. In the late stages of ALS, the muscles necessary for breathing weaken, resulting in death. There are two forms of this disease: sporadic and familial. The former is the most common, with 90-95% of cases falling into this category.
Medical professionals do not know the cause of ALS. In the familial form of the disease it is known that a mutated gene is inherited from parents, but it is still not fully understood and only accounts for 5-10% of cases. Researchers believe that there is a connection between frontotemporal dementia and ALS. Another theory is that exposure to certain substances or toxins leads to the development of ALS.
Symptoms of ALS vary between individuals. They also worsen as the disease progresses. Symptoms begin with difficulty with small movements and everyday things like walking. At the onset of the disease, people may trip and feel weakness in their arms, hands, and legs. As it progresses, people experience difficulties with speaking and swallowing, slowed and slurred speech, twitches and cramps in the muscles, and difficulty holding good posture. In the later stages people will be unable to move their muscles gradually, which affects the entire body. This inability affects movements like blinking. While people with ALS experience loss of muscle function, they do not lose any of their cognitive abilities.
About the Study
The upcoming study will evaluate trehalose, also known as SLS-005. It is a low molecular weight disaccharide that is able to stabilize proteins, activate autophagy, and cross the blood-brain barrier. It does so by activating transcription factor EB. As mutations in certain genes, namely the C9orf72, SOD1, FUS, and TARDBP genes, cause familial ALS and contribute to sporadic ALS, trehalose also aims to address these mutations.
Researchers hope that the upcoming study will show the same success as pre-clinical trials, which showed that trehalose can prevent the degeneration of motor neurons, improve motor function, and prolong survival.
The phase IIB/III trial is looking to enroll 160 ALS patients. It will be placebo-controlled and double-blind, and participants will be randomized 3:1. The primary endpoint is improvement based on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Secondary endpoints include improvements in muscle strength, quality of life, disease progression, and slow vital capacity.
Hopefully this trial is successful, as ALS is a disease with an unmet medical need. If trehalose is a viable therapy for ALS, then patients may have a new, more effective therapy.
Read more about this study here.