Project Portfolio
This page summarizes all the projects being done.
GNAO1 (Tyanasen) is antisense oligonucleotide based therapy that targets one of the most common GNAO1 mutants c.607G>A p.G203R. Clinical trials are due to begin in Europe this year.
GNAO1 ASO (Tyanasen)
GNAO1 Gene Therapy will replace GNAO1 gene with a new copy. We are testing several modalities to replace isoform 1, isoform 2, dual isoform construct as well as miRNA sequence to silence indigenous GNAO1 (including mutant allele). This treatment aims to help all children with GNAO1 encephalopathy.
GNAO1 Gene Replacement
CDKL5 Drug Repurposing
The high mortality rate associated with CDKL5 remains uncertain in its direct attribution to the protein deficiency or the disorder’s challenges. Recent developments have shown promise with a treatment plan involving a CDKL2 medication, which shares similar functions with CDKL5. Collaboration with Rarebase, PBC, identified molecules activating CDKL2, tested successfully on CDKL5 mouse models, and led to significant improvements in children, with efforts underway to introduce the medication more broadly and initiate a clinical trial at NYU Langone.
CDKL5 Drug Repurpusing
CDKL2
One of the primary concerns associated with the CDKL5 diagnosis is the high mortality rate linked to this condition. It remains uncertain whether this is directly attributed to the CDKL5 protein deficiency itself or the inherent challenges of the disorder.
However, recent developments have provided a glimmer of hope. Recently, a treatment plan was initiated involving medication designed for CDKL2, rather than CDKL5. CDKL5 and CDKL2 share similar functions, with CDKL5 typically taking precedence while CDKL2 remains dormant.
Collaboration with Rarebase, PBC, led to the identification of promising molecules capable of activating CDKL2. These molecules were then tested on CDKL5 mouse models at the Royal College of Surgeons in Ireland, yielding promising results. Notably, one of these molecules happened to be an FDA-approved medication already used as an adjunct therapy for epilepsy, boasting well-studied safety and efficacy profiles. This is the first treatment developed specifically for CDKL5, tested on CDKL5 mutant cell lines and mice models.
Under the guidance of a Stanford neurologist Dr. William Gallentine, an off-label prescription for this CDKL2 medication was obtained for a child and concurrently, for another child from Rainbow Children’s Hospital, in Hyderabad. Since then, significant improvements have been observed, with a major reduction in seizures and notable developmental progress. However, it’s essential to recognize that this treatment represents effective management rather than a cure.
Efforts are underway to introduce this medication to children in the US, India, and Canada.
Clinical trial:
Rainbow Children’s Hospital, Hyderabad, India (started).
Principal Investigators: Dr. Lokesh Lingappa & Dr. Prasanthi Aripirala.
John Hopkins, USA (in pipeline).
Principal Investigators: Dr. Christopher Mario Ingeles.
CDKL5 AAV9 Gene Therapy
Next step – clinical trials.