The Disney group is focused on developing rational and predictable approaches to design highly selective therapeutics from only genome sequence. One of the major articulations of the utility of genome sequencing efforts has been in advancing patient-specific therapies, yet such developments have been only sparsely reported.
We accomplish this lofty goal by using advancements in annotating RNA structure from sequence and several novel technologies that we have recently developed in our laboratory. Our current focus is on leveraging these technological advances to identify patient-specific therapies targeting orphan diseases that have no known cure or more common disorders to which there is a poor prognosis, such as drug resistant cancers.
Key advances that we have recently reported include:
(i) Developing lead therapeutics that improve defects associated with the most common adult-onset forms of muscular dystrophy (Myotonic Dystrophy Types 1 and 2) in both animal and cellular models of disease.
(ii) Designing compounds that target the most common single gene cause of Autism (Fragile X Syndrome) and an adult-onset disease called Fragile X-Associated Tremor Ataxia Syndrome that occurs in older individuals that carry a shortened version of the Fragile X Syndrome genetic defect. These studies have advanced our understanding of novel roles of RNA-mediated gene silencing and in identifying and exploiting novel drug targets.
(iii) Targeting the genetic defect that causes Huntington’s disease, which is an incurable disorder that causes muscle decline and cognitive issues.
(iv) Correcting RNA processing defects that are caused by RNA mutations in Parkinsonism and Frontotemporal Dementia (FTDP-17).
(v) Developing specific lead therapeutics that reduce the production of toxic proteins that are known to cause the majority of cases of Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s disease) and Frontotemporal Dementia
(vi) Designing precise therapeutics that specifically kill a variety of Cancers that have a poor prognosis with current chemotherapeutics
(vii) Exploiting important classes of drug targets in multiple disorders that are viewed as being impossible to “drug”
(viii) Developing and implementing novel technologies that allow for the precise reaction and cleavage of RNA targets by using small molecules to both identify and further manipulate therapeutically relevant RNAs by small molecules.