Neurology

Cell culture and mouse studies suggest inhibiting SQSTM1 could help treat SMA, which is caused by SMN1 mutations. In motor neuron cells derived from a mouse model of SMA or from two SMA patients, shRNAs targeting SQSTM1 increased SMN1 protein levels compared with non-SQSTM1-targeting shRNAs. In a mouse model of SMA, heterozygous SQSTM1 knockout increased transverse abdominal muscle fiber size and innervation, the number of motor neurons in the spine, body weight and survival compared with normal SQSTM1 expression. Next steps could include identifying SQSTM1 inhibitors and testing them in SMA models.

Soligenix Inc. has dusquetide (SGX94, SGX942, imx942), a synthetic 5-amino acid peptide that binds to SQSTM1, in Phase III testing for mucositis and Phase II testing for head and neck cancer. ...