PTC Therapeutics, Inc., a global biopharmaceutical company, has entered into a research collaboration with Massachusetts General Hospital (MGH, a Partners Healthcare hospital) for the treatment of rare genetic disorders resulting from pre-mRNA splicing defects. The collaboration reflects both parties' commitment to improving the lives of those who suffer from rare and neglected diseases.

Under the terms of the agreement, PTC gains an exclusive worldwide license to compounds that modulate alternative splicing of the IKBKAP pre-mRNA - the predominant cause of familial dysautonomia (FD), also known as Riley-Day syndrome, a rare life-threatening genetic disorder. PTC will pay an upfront license fee, make payments upon successful completion of certain development and commercialisation milestones, as well as royalties on worldwide product sales. PTC will fund collaborative research and licensing activities, as well as be responsible for the development and commercialisation of products arising from the collaboration.

"We are excited to collaborate with PTC Therapeutics," said Susan Slaugenhaupt, scientific director of the Mass General Research Institute, professor of neurology (genetics) at Harvard Medical School, and the Elizabeth G. Riley and Dan E. Smith, junior. MGH research scholar in the MGH Center for Human Genetic Research.

"PTC's leadership in developing treatments for rare diseases and expertise in RNA biology, combined with our innovative research capabilities, makes this a powerful collaboration to carry forward our research program to develop therapies for splicing-related genetic conditions."

Dr. Slaugenhaupt's research has been supported by a grant under the National Institutes of Health (NIH) Blueprint for Neuroscience Research. Early research in her laboratory on splicing therapies was also funded by the Dysautonomia Foundation, Inc.

"We are thrilled to build on the excellent research being conducted at MGH and expand our RNA platform in alternative splicing," said Neil Almstead, Ph.D., executive vice president, research, pharmaceutical operations and technology at PTC Therapeutics.

"Dr. Slaugenhaupt's pioneering work into the genetic mechanisms behind familial dysautonomia and other potential diseases present a strong fit for both our expertise in RNA biology and our mission to develop medicines for people with rare and neglected diseases."

PTC has developed a platform technology that enables discovery and development of drugs that modulate pre-mRNA splicing. The most advanced program built on this platform is in clinical development for spinal muscular atrophy in collaboration with Roche and the SMA Foundation.

Familial dysautonomia (FD), also known as Riley-Day syndrome and HSAN type III, is a rare, life-threatening genetic disease that affects the autonomic and sensory nervous systems of children from birth. It affects every major system of the body, causing severe respiratory, cardiovascular, orthopedic, digestive, renal, and vision problems. The most striking symptoms of FD are reduced sensitivity to pain and temperature, and the inability to produce tears. Children with FD suffer from chronic and often debilitating symptoms that prevent them from leading normal lives.

FD is caused by mutations in the IKBKAP gene. Most FD patients are homozygous for a single nucleotide mutation in intron 20 that leads to alternative splicing of exon 20 and low levels of IKAP protein, predominantly in the nervous system. This mutation leads to reduced protein expression in all tissues, with the most significant reduction in neuronal tissue.