While Ethris’ SNIM® RNA technology could have applications in many diseases, including metabolic and/or hereditary diseases, and in regenerative medicine, the Company focuses its proprietary development activities on respiratory diseases. In its current lead indication, primary ciliary dyskinesia or PCD, Ethris is developing a series of therapeutic mRNA programs that are designed to potentially alleviate disease symptoms and slow down the progression of the disease over the patient’s life time.
PCD – Primary Ciliary Dyskinesia
Individuals with primary ciliary dyskinesia face significant daily challenges that impact their quality of life. Beginning with a high likelihood of neonatal acute respiratory distress, patients throughout their lives cannot clear respiratory secretions normally. This leads to long term chronic rhinitis (runny nose), and frequent sinus and ear infections, with long term sequelae including development of nasal polyposis and impaired hearing. In addition, patients develop a chronic cough and may experience recurrent infections of the lower respiratory tract leading to long term structural lung damage with reductions in lung function. In some cases, the pulmonary damage is so severe that lung transplantation is required.
Current PCD treatments are limited to treatment of symptoms. Regular physical therapy and the inhalation of hypertonic saline are employed to aid in removal of excess mucus in the airways, and antibiotics are used to treat infections, but there are currently no available therapies that address the underlying cause of disease or alter disease progression over time.
Cilia – a biological conveyor belt
The cells that line our airways are equipped with tiny hair-like organelles called cilia, which beat synchronously to form a biological conveyor belt that continuously moves respiratory secretions and foreign debris upwards in the respiratory tract and away from the lungs.
Normal clearance of mucus via the synchronised movement of cilia.
PCD – the conveyor belt jams
Mutations in the genes that code for ciliary proteins can result in a disorder called Primary Ciliary Dyskinesia (PCD), in which the cilia have structural defects or are even absent entirely. With the cilia unable to fulfill their crucial role in the respiratory system, mucus loaded with trapped microbes, dust, and other debris cannot be cleared from the airways efficiently. The accumulation of mucus causes the symptoms of rhinitis and cough and impairs daily activity and quality of life, and microbes that are not cleared can establish infections that require short or long-term antibiotic treatment.
Accumulation of mucus in the airways due to defective cilia.
Our approach using mRNA therapeutics
At Ethris, we’re leveraging our breakthrough SNIM® RNA technology to develop messenger RNA therapeutics that treat PCD by restoring normal ciliary function, getting the conveyor belt moving again.
Our strategy is to initially target one of the more prevalent genes behind PCD that, when defective, results in production of a faulty ciliary structural protein. With our SNIM®RNA technology we can introduce a corrected mRNA for this gene to critical cells in the airways, which can be delivered by nebulization. These cells would then have the correct blueprint for growing normal functional cilia, leading to restoration of mucus clearance mechanisms, reduced inflammation, and prevention of infections that lead to long term structural damage.
Delivery of corrected mRNA to maturing epithelial cells in the airways via our SNIM® RNA technology, leading to growth of normal functional cilia.