There are many things that make PTC Therapeutics truly unique, and the splicing platform is one of them.

Here, “splicing” refers to PTC’s scientific platform that takes aim at modulating pre-messenger RNA (pre-mRNA) splicing to control protein production. This scientific platform together with the technology that powers it, enables the identification of small molecules, which are known as splicing modifiers, that are designed to strengthen the interaction between the cellular splicing machinery and the pre-mRNA to help make splicing more efficient.

PTC pioneered the idea that splicing can be modulated utilizing small molecules, built on the team’s expertise in RNA biology. Over the last 20 years, the PTC research team has perfected the RNA splicing technology. Using this technology, the team successfully identified an oral small molecule for the treatment of spinal muscular atrophy (SMA) – the first ever small molecule approved to specifically target splicing. The treatment targets and encourages a faulty exon in the SMN2 ‘back-up’ gene to produce a greater amount of functional SMN protein.

Our expertise in RNA biology was critical for the discovery of the SMA treatment. It was this expertise that led us to develop technology to target splicing and allowed us to move forward with this scientific platform.
Chris Trotta Senior Vice President, Biology

The PTC research team has also applied the splicing platform to Huntington’s disease (HD) for a potential treatment for HD called PTC518. HD is a rare disease caused by a defect in the HTT gene which produces a mutated HTT protein. PTC518, a small molecule that can be taken orally, induces the inclusion of a very weak exon with a premature stop codon to become part of the HTT mRNA. This splicing modification prevents the production of the full length HTT protein and causes rapid degradation of the HTT mRNA. PTC518 has demonstrated a dose dependent reduction in HTT mRNA and protein.

“The learnings from our discovery process in SMA and HD have allowed our discovery team to make the types of hypotheses to get us to the next level,” says Suresh Babu, Senior Research Fellow, Chemistry. “These important insights will help us determine how we find the next molecule.”

PTC’s approach to drug discovery, and the passionate research team employing this technology, led to the creation of these compounds.

“We don’t just take one shot when it comes to drug discovery,” says Matt Woll, Senior Vice President, Chemistry. “Ultimately, the science will tell us the best approach, but we have to try many times to get there.”

The discovery process and the way the platform is optimized for the treatment of rare diseases is also a product of cross-functional collaboration.

The culmination of many efforts comes together in one molecule. We all work together toward one goal, and there is a whole team behind one molecule.
Anu Bhattacharyya Vice President, Biology

PTC’s RNA splicing technology has broad potential to identify new treatments for patients suffering from a variety of diseases. We continue to identify novel small molecules that modify splicing of disease-relevant genes, either by promoting inclusion of specific exons or by forcing an exon to be skipped. PTC scientists will continue to leverage our innovative RNA splicing platform to discover new therapies that address the underlying causes of life-limiting diseases. 

“We are illuminating a new area in splicing,” says Chris. “We have the experience and know-how to avoid roadblocks along the drug discovery process. We are applying all of this as we work hard to get to the next discovery of a molecule.”