Mutations located on the thymidine phosphorylase gene (TYMP) result in several pathological conditions known as mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder characterized by pronounced gastrointestinal and neurological symptoms. Dedicated to helping advance research and therapy of MNGIE, Protheragen provides detailed and comprehensive services to facilitate research.
Introduction to MNGIE
MNGIE is a multi-system disorder, also referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, intestinal pseudo-obstruction (POLIP), oculogastrointestinal muscular dystrophy (OGIMD), mitochondrial myopathy with sensorimotor polyneuropathy, ophthalmoplegia and pseudo-obstruction syndrome (MEPOP). MNGIE is usually caused by a mutation in the TYMP that is responsible for encoding thymidine phosphorylase. This change in genetics causes decreased activity of thymidine phosphorylase which results in excessive thymidine and deoxyuridine in the human body. Thus, there is blockage of synthesis and repair of mitochondrial DNA, and the function of mitochondria which is usually affected in tissues of high energy demand like intestine and nerves is decreased.
Fig.1 MRI (magnetic resonance imaging) view shows marked leukoencephalopathy in a MNGIE. (Filosto, M., et al., 2018)
Research Progress of MNGIE
The focus of the researchers is to enhance the knowledge of the pathophysiological mechanisms underlying MNGIE. With the increase in cell and molecular biology, the detection and identification of mutations in genes vital to MNGIE have greatly improved. Animal and cell models are being used to study the pathogenesis of the disease in question 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 remedial alternatives comprise hemodialysis (HD), continuous peritoneal dialysis (CAPD), artificial enzyme replacement therapy (EE-TP), and transfusion of platelets. Although these methods are capable of providing some relief to biochemical imbalances, their implementation comes with practical restraints, safety risks, and unclear effects.
Permanent Therapies
Both hematopoietic stem cell transplantation (HSCT) and orthotopic liver transplantation (OLT) can restore biochemical balance permanently. However, the execution of HSCT involves chemotherapy and immunosuppressive therapy. In comparison, while OLT does not have preoperative requirements, it does have lower overall mortality during therapy.
Our Services
Protheragen is an excellent partner for drug research and development for MNGIE, an exceedingly rare and intricate mitochondrial disorder. To support your efforts to achieve notable advancements in this domain, we offer a comprehensive range of MNGIE research services.
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
At Protheragen, we offer the services that come at the preclinical level so that your focus can be directed primarily towards research goals. Should you need to ask questions about our services or are interested in what we offer, 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.
