Type IV, adult-onset SMA usually means only mobility impairment and does not affect life expectancy. Research directions
Since the underlying genetic cause of SMA was identified in 1995, several therapeutic approaches have been proposed and investigated that primarily focus on increasing the availability of SMN protein in motor neurons. The main research directions have been as follows:

SMN1 gene replacement
Gene therapy in SMA aims at restoring the SMN1 gene function through inserting specially crafted nucleotide sequence (a SMN1 transgene) into the cell nucleus using a viral vector. This approach has been exploited by the first approved gene therapy for SMA, scAAV-9 based treatment onasemnogene abeparvovec. SMN2 alternative splicing modulation
This approach aims at modifying the alternative splicing of the SMN2 gene to force it to code for higher percentage of full-length SMN protein. Sometimes it is also called gene conversion, because it attempts to convert the SMN2 gene functionally into SMN1 gene. It is the therapeutic mechanism of the approved medications nusinersen and risdiplam. Branaplam is another SMN2 splicing modulator that has reached the clinical stage of development.Historically, this research direction investigated also other molecules. RG3039, also known as Quinazoline495, was a proprietary quinazoline derivative developed by Repligen and licensed to Pfizer in March 2014 which was discontinued shortly after, having only completed phase I trials. PTK-SMA1 was a proprietary small-molecule splicing modulator of the tetracyclines group developed by Paratek Pharmaceuticals and about to enter clinical development in 2013 which however never happened due to Paratek downsizing at that time.
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures.The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types.Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene which encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles. Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing.Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo).