Experimental Treatments for SMA
Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder characterized by progressive muscle weakness. SMA patients do not produce enough of a protein called survival motor neuron (SMN), due to a mutation in the SMN1 gene. Another gene, SMN2, also can produce some SMN protein, but it is less stable.
A number of experimental therapies are in the pipeline for the potential treatment of SMA. These include treatments aimed at increasing SMN protein levels, enhancing residual SMN function, and compensating for its loss. Some of the therapies currently in development for SMA are summarized below.
Apitegromab (SRK-015) is a laboratory-made monoclonal antibody that works to block the activation of a skeletal muscle protein called myostatin. When injected into the bloodstream, apitegromab selectively binds to latent myostatin. This binding prevents the conversion of myostatin to its active form in muscle tissues, potentially improving muscle strength and motor function in SMA patients. It is currently under investigation in a Phase 2 trial.
Branaplam (also known as LMI070 or NVS-SM1) is a potential treatment being developed for babies newly diagnosed with SMA type 1. It is designed to increase the amount of functional SMN protein produced from the SMN2 gene. In mouse models of SMA, it was found to increase amounts of SMN protein, leading to improvements in body weight and survival of the animals. The potential therapy currently is being tested in a Phase 1/2 trial.
Reldesemtiv (formerly CK-2127107) is an investigational therapy that may improve muscle function and physical performance in people with SMA or amyotrophic lateral sclerosis (ALS). It works by slowing the rate of calcium release from a group of proteins called the regulatory troponin complex, potentially increasing the capacity of skeletal muscles to contract. It has completed a Phase 2 trial with positive results.
Valproate is approved by the U.S. Food and Drug Administration for the treatment of epileptic seizures, episodes associated with bipolar disease, and for the prevention of migraines. Previous research has shown that when valproate was added to cells from SMA patients under laboratory conditions, the levels of the SMN protein increased. Valproate has been studied in numerous clinical trials for SMA.