University of Pittsburgh researchers have developed a novel treatment for treating disease conditions that result from deficiency of succinyl-CoA including propionic acidemia and fatty acid disorders.
Description
A series of polypeptide molecules containing a modified adipic moiety part has been developed to increase precursors of succinyl-CoA and promote key pathological pathways.
Applications
1. Propionic acidemia, a genetic metabolic disorder is caused by deficiency of propionyl-CoA carboxylase (PCC). PCC is a mitochondrial enzyme responsible for a vital step in the breakdown of fatty acids and amino acids and may present in the first week of life with early onset linked to high mortality.
2. Diseases resulting from the deficiency of succinyl-CoA.
3. Methylmalonic acidemias.
4. Fatty acid oxidation disorders including CPT II, TFP, LCHAD, VLCAD and MCAD deficiencies.
5. Disorders involving intermediates of the tricarboxylic acid cycle (Krebs/Citric Acid cycle).
Advantages
Currently there is no known cure and therapy for acidemias involves treatments of multiple systems including shock, acidosis, and glucose levels along with severe restrictions on protein intake. In severe cases, liver and/or kidney transplantation may be required.
This novel approach would allow for targeting of the underlying pathophysiology by providing a key requirement of the citric acid cycle and maintain succinyl-CoA at its physiologically optimal levels.
Invention Readiness
Proof of concept testing has been carried out in vitro on fibroblast cells from patients with propionic acidemia and methylmalonic acidemias, with established efficacy of the anaplerotic compounds at a cellular level.
IP Status
https://patents.google.com/patent/WO2024030367A2
