This morning I received an email from a CurePSP support group leader in Texas forwarding a local newspaper clipping about a young girl in Taiwan with a genetic metabolic defect of the brain who had received a form of gene therapy.  She asked if that approach could be of potential use against PSP.

Here’s my answer:

For decades, a routine neuroscience laboratory tool has been to inject the brain with a harmless virus, called a “vector,” carrying a gene to induce brain cells to manufacture that gene’s protein product.  This has been useful in PSP research. Before long, the same idea could become a treatment for patients with neurodegenerative diseases.  The main drawback is that it requires a neurosurgical procedure to inject the virus with the therapeutic gene into the specific spot(s) in the brain where it’s needed. 

This approach has worked in early-phase trials in people with Parkinson’s disease, where cells that make dopamine are degenerating, and is continuing safety studies in PD.  The gene in those trials encodes the enzyme AADC (aromatic amino acid decarboxylase), which controls dopamine’s rate of production.  AADC mutations do not occur in PD, but the girl in Taiwan who received the gene therapy was suffering from an inherited deficiency of AADC, causing delayed neurological development. 

This sort of gene therapy, but using MAPT, the gene for the tau protein, has been used in PSP research to produce a rat model for use in testing new treatments.  The company sponsoring the AADC deficiency trial in Taiwan is developing an MAPT gene therapy for the rare form of frontotemporal dementia caused by mutations in MAPT, called FTDP-17.  Unfortunately, PSP, unlike AADC deficiency or FTDP-17, is not caused by a single mutation in a known gene, so it would not be amenable to having that gene replaced by this sort of gene therapy.  It’s true that PSP, like PD, includes a dopamine deficiency, but PSP would not respond to AADC gene therapy for the same reason it doesn’t respond to L-DOPA (which is converted by the body into dopamine): the brain cells on which dopamine acts degenerate in PSP. 

The hopeful note, however, is that if a compound such as a growth factor protein or an anti-sense oligonucleotide (ASO) is found to help PSP, a gene for that compound could, in theory, be inserted into a viral vector and injected into the brain.  That could provide a steady, lifetime supply of the compound.