The autosomal recessive disorder known as mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene (TYMP), resulting in severe gastrointestinal (GI) and neurological symptoms. Protheragen is dedicated to offering comprehensive research services aimed at advancing the understanding and treatment options for MNGIE.
Introduction to MNGIE
MNGIE, also referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction (POLIP), oculogastrointestinal muscular dystrophy (OGIMD), mitochondrial myopathy with sensorimotor polyneuropathy, ophthalmoplegia and pseudo-obstruction syndrome (MEPOP), is a multi-system disorder. MNGIE is usually caused by to a mutation in the TYMP gene, responsible for encoding thymosylphosphatase. This genetic alteration results in reduced activity of thymoadenylate phosphatase, leading to an accumulation of deoxythymoadenylate and thymoadenylate within the body. Consequently, the synthesis and repair of mitochondrial DNA are adversely affected, resulting in impaired mitochondrial function primarily observed in high-energy-demanding tissues such as nerves and intestines.
Fig.1 MRI (magnetic resonance imaging) view shows marked leukoencephalopathy in a MNGIE. (Filosto, M., et al., 2018)
Research Progress of MNGIE
The researchers aim to gain a deeper understanding of the pathophysiological mechanisms underlying MNGIE in order to develop more efficacious treatments. Advances in molecular biology and genomics have facilitated the identification and diagnosis of mutations in genes associated with MNGIE. Researchers are utilizing animal and cellular models to investigate the disease's pathogenesis and identify potential therapeutic targets.
Novel Diagnostic Methods of MNGIE
Some recent advancements have been achieved in the diagnosis of MNGIE.
Clinical Features
The clinical presentation of MNGIE encompasses neurogastrointestinal symptoms and signs, cachectic posture, as well as progressive neurological manifestations including external ocular muscle palsy and sensory neuropathy.
Biochemical and Genetic Testing
This includes measurement of plasma and urine deoxythymidine (dThd) and deoxyuridine (dUrd) levels, along with sequencing analysis of the TYMP gene. Mutations in the TYMP gene represent one of the primary genetic etiologies underlying MNGIE.
Nerve Conduction Studies
Nerve conduction studies can be employed to assess patients for peripheral neuropathy, typically presenting with predominant demyelination.
Imaging
Brain MRI can reveal bilateral symmetric white matter demyelinating lesions, which are characteristic findings in MNGIE aiding in the diagnostic process.
Fig.2 Diagnostic algorithm in MNGIE. (Hirano, M., et al., 2021)
Novel Therapies of MNGIE
Some recent advancements have been achieved in the therapies of MNGIE.
Short-Term Therapies
The available treatment options encompass hemodialysis (HD), continuous peritoneal dialysis (CAPD), artificial enzyme replacement therapy (EE-TP), and platelet transfusion. While these approaches can provide temporary amelioration of biochemical imbalances, practical limitations, safety concerns, and ambiguous clinical effects are associated with their implementation.
Permanent Therapies
Hematopoietic stem cell transplantation (HSCT) and liver transplantation (OLT) can effectively restore biochemical balance in a permanent manner. HSCT necessitates chemotherapy and immunosuppressive therapy, which are accompanied by significant treatment-related complications and mortality rates. On the other hand, OLT does not require preoperative conditions and is associated with a lower mortality rate during treatment.
Our Services
Protheragen is a formidable partner in your pursuit of resolving MNGIE, an uncommon and intricate mitochondrial disorder. We provide an extensive array of MNGIE research services meticulously crafted to bolster your endeavors in achieving groundbreaking advancements in this domain.
Mitochondrial Disease Diagnostics Development Service
During the diagnostic phase of MNGIE, we provide a comprehensive range of diagnostic development services to facilitate accurate disease identification.
Therapeutics Development Services for Mitochondrial Diseases
The provision of our treatment development services for MNGIE reflects our unwavering commitment to delivering efficacious therapeutic options for this disease.
Our Advantages
With Protheragen' professional services, you can confidently focus on your research objectives without being burdened by the challenges of the preclinical phase. If you are interested in our services or have any inquiries, please do not hesitate to contact us.
References
- Filosto, M.; et al. (2018). Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1). Journal of clinical medicine, 7(11), 389.
- Hirano, M.; et al. (2021). Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. Journal of inherited metabolic disease, 44(2), 376–387.
