Telomerase mRNA for short telomere related pulmonary fibrosis
Grant Award Details
Grant Type:
Grant Number:
TRAN1-14623
Investigator(s):
Disease Focus:
Award Value:
$3,984,942
Status:
Active
Grant Application Details
Application Title:
Telomerase mRNA for short telomere related pulmonary fibrosis
Public Abstract:
Translational Candidate
Nucleoside-modified mRNA encoding telomerase reverse transcriptase (TERT) encapsulated in a lung-targeting lipid nanoparticle delivered intravenously.
Area of Impact
1) Idiopathic pulmonary fibrosis (IPF) and 2) Other diseases and conditions caused or exacerbated by short telomeres.
Mechanism of Action
TERT mRNA LNPs transiently extend the telomeres of the alveolar epithelial cells of the lung, enabling the cells to divide to repair the lung structure and function, and delaying cellular senescence and the chronic secretion by the senescent cells of inflammatory pro-fibrotic molecules. The extension of the telomeres occurs over a few hours, after which the extended telomeres resume shortening at their normal rate. The telomere extension that occurs reverses years of telomere shortening.
Unmet Medical Need
Idiopathic pulmonary fibrosis is a fatal disease brought on by shortened telomeres that results in death by gradual suffocation, with median survival of only 3–5 years following diagnosis. Our one-shot treatment delivers a therapy that extends telomeres by transiently boosting telomerase activity.
Project Objective
The performance of IND-enabling studies.
Major Proposed Activities
Nucleoside-modified mRNA encoding telomerase reverse transcriptase (TERT) encapsulated in a lung-targeting lipid nanoparticle delivered intravenously.
Area of Impact
1) Idiopathic pulmonary fibrosis (IPF) and 2) Other diseases and conditions caused or exacerbated by short telomeres.
Mechanism of Action
TERT mRNA LNPs transiently extend the telomeres of the alveolar epithelial cells of the lung, enabling the cells to divide to repair the lung structure and function, and delaying cellular senescence and the chronic secretion by the senescent cells of inflammatory pro-fibrotic molecules. The extension of the telomeres occurs over a few hours, after which the extended telomeres resume shortening at their normal rate. The telomere extension that occurs reverses years of telomere shortening.
Unmet Medical Need
Idiopathic pulmonary fibrosis is a fatal disease brought on by shortened telomeres that results in death by gradual suffocation, with median survival of only 3–5 years following diagnosis. Our one-shot treatment delivers a therapy that extends telomeres by transiently boosting telomerase activity.
Project Objective
The performance of IND-enabling studies.
Major Proposed Activities
- Pharmacokinetics (PK) and dose determination of i.v.-injected TERT mRNA LNPs.
- Pharmacodynamics (PD), biomarker, and comparative studies to FDA approved IPF drugs and Pharmacology in IPF patient cells.
CMC activities (scale-up, assay methods and stability) for manufacturing of TERT mRNA LNP production.
Statement of Benefit to California:
Idiopathic pulmonary fibrosis is a serious illness with no cure for which there is a high unmet medical need for treatment. In the US, the vast majority of patients with reported idiopathic pulmonary fibrosis (IPF) are non-Hispanic whites yet Hispanic populations have earlier onset and worse outcomes of the disease, as do minority patients in general. The relatively high numbers of Hispanic citizens in California make this disease one of particular interest to the medical community in the State.
