Inborn errors of metabolism (IEMs) disrupt biochemical pathways through deficiency of a particular enzyme. This deficiency results in blocked downstream pathways due to a lack of required metabolites, accumulation of the enzyme’s substrate or an accumulation of alternative metabolites, all of which can be life-threatening.
Description
This novel approach aims to identify the molecular cause of each IEM and tailor treatments to target the impacted biochemical pathways, leading to personalized treatments with improved patient outcomes and quality of life.
Applications
1. Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency
2. Medium acyl-CoA dehydrogenase (MCAD) deficiency
3. Trifunctional protein (TFP) deficiency
4. Other IEM-related disorders
Advantages
Current approaches to treating IEMs are limited and often focused on diet management or restrictions on exercise to reduce the presence of substrates for mutated enzymes or thermal instability of proteins produced by mutated enzymes. These can impact on patients’ quality of life, are not always effective, and are an unmet clinical need in individuals with IEMs.
This novel approach aims to inhibit the activity of enzymes involved in reactions downstream of the defective enzyme. By blocking downstream enzymatic processes, a buildup of the mutated enzyme’s substrate or products occurs and can bind to various sites (active or allosteric) on the mutated enzyme, alleviating the genetic disorder phenotype. The exact biochemical pathway impacted by an IEM can be identified and targeted using molecular and cellular testing platforms, leading to personalized, comprehensive treatment for a wide variety of IEMs.
Invention Readiness
In vitro experiments have shown deficiencies in VLCAD and MCAD can be overcome through treatment with TMZ. Further in vivo testing required.
IP Status
https://patents.google.com/patent/US20240075025A1
