Science
Aptah is a biotech startup focused on novel RNA therapies initially targeting cancer and neurodegenerative diseases.
By understanding the mechanisms underlying sporadic neurodegenerative and oncology diseases, we developed and patented a new technology platform called ASMO - Aptah Spliceosome Modulation Oligonucleotide - which is the backbone to produce innumerous synthetic molecules, rationally designed to modulate (not silence), in an unique way, specific proteins called snRNPs - small ribonucleoproteins (or RNA binding proteins), key elements responsible for protein aggregation, protein synthesis and many other physiological functions, thus, paving the way for the treatment of thousands of genetic disorders.
Our research focuses on the central concept of regulated protein-protein interaction and aggregation. Protein aggregation in neurodegenerative diseases and oncology is thought to occur as an unwanted byproduct of protein misfolding. Recent studies increasingly highlight the importance of RNA binding proteins and protein aggregation as part of a normal regulated, physiological mechanism controlling protein synthesis as well as many fundamental physiological functions, such as stress granules, transport granules and P bodies.
Our hypothesis is that dysfunction of snRNPs causes neurodegenerative diseases and cancer. Aggregation, over activation and mislocalization of snRNPs could contribute to neurodegeneration and cancer by altering patterns of protein synthesis, post translational modifications and arresting proteins that regulate autophagy, organelles transport, cell proliferation, growth and migration.
The ASMO platform comprises a new class of molecules capable of interacting in an innovative and versatile way with both multiple proteins and the transcript (pre-mRNA) at the same time, which allows the development of a completely new modality of therapies for the treatment of genetic disorders currently untreated, such as several oncological and neurodegenerative diseases.
ASMOs are not limited to the capabilities of the antisense oligos currently used to correct aberrations arising from specific mutations, but encompass a much broader capacity to address epigenetic dysfunctions, such as protein-protein interaction, unrelated to a specific base mutation, but to an epigenetic effect. Among its capabilities, the ASMO platform can meet customized goals such as preventing abnormal splicing linked to a specific mutation, preventing abnormal splicing linked to a dysfunction of splicing components common to all genes, or controlling expression levels of target transcript for different types of diseases, modulating this transcript(s) without silencing or inhibiting it, which makes the treatment much safer.
In competing technologies, such as those involving the use of antisense oligonucleotides (ASO) or RNA interference, the main focus is on inhibition, silencing or degradation methods of a specific site at the pre-mRNA or mRNA of a specific gene. Such approaches make sense for genetic diseases associated with mutations at specific sites, such as in intronic or exonic regions, allowing, for example, the silencing or degradation of isoforms of transcripts containing the mutation. However, such an approach is not suitable for diseases that do not involve single mutations, or for those which involve generalized dysfunctions (such as abnormal snRNPs aggregates), which can be strategically addressed by our technological platform.
