Ace Therapeutics

Diabetes mellitus is a chronic, systemic, metabolic disease caused by the long-term combination of genetic factors and environmental factors, characterized by increased plasma glucose levels, mainly due to insufficient insulin secretion or dysfunction in the body (insulin resistance). The disorder of sugar, fat and protein metabolism caused can affect normal physiological activities and manifest as a variety of acute and chronic complications.

Classification of Diabetes

Diabetes is a chronic (long-lasting) health condition that affects how your body turns food into energy. When blood sugar goes up, it signals the pancreas to release insulin. The main diabetes types include type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes (diabetes while pregnant) and other special types of diabetes (the diabetes caused by all causes except T1DM, T2DM and GDM).

Complications of Diabetes

All forms of diabetes increase the risk of long-term complications. The serious harm of diabetes is to cause many complications, including infectious diseases, atherosclerosis, microvascular disease, neurological complications and so on. The number of diabetes related deaths worldwide is about 1.5 million per year. It can be seen that diabetes is an area worthy of in-depth research, and more pathological research and therapy development are still needed.

Advances in Diabetes Therapies

Recombinant insulin and insulin analogs are the main drugs for clinical treatment of diabetes. In addition, there are new treatment methods such as islet/pancreas transplantation, cell and gene therapy, but the technical methods are cumbersome and need to solve problems such as immune rejection.

Distribution of R&D Companies

The global research and development of diabetes treatment drugs is mainly dominated by multinational pharmaceutical companies. They are mainly Novo Nordisk, Eli Lilly, Medtronic, Sanofi, Roche, Johnson & Johnson, Korea INFOPIA, Abbott, Panasonic Healthcare, France Biotech company ADOCIA, etc.

R&D Trends

There are nearly 3,000 diabetes treatment drugs in all stages of global research and development (including under development, suspension, withdrawal, and termination), of which about 1,500 are for T2DM and about 400 are for T1DM. And a small number of drugs are used for the treatment of special types of diabetes, such as gestational diabetes, latent autoimmune adult diabetes, etc.

The Drugs in Clinical Research

In addition to hypoglycemic drugs such as metformin, which are already widely used in treatment, the field of diabetes research continues to explore therapies. Recombinant insulin and insulin analogs are the main drugs for clinical treatment of diabetes. There are some immunotherapy drugs in clinical research for diabetes.

Protein aggregation of α-synuclein and hyperphosphorylated tau proteins in neurodegenerative diseases have been shown to be triggered in vitro by elevated concentrations of trivalent iron. Inclusion bodies containing damaged or aggregated proteins may lead to endoplasmic reticulum stress, a common feature of several neurodegenerative disorders.

Alzheimer\'s Disease: High levels of iron are present in insoluble amyloid plaques and neurogenic fiber tangles characteristic of Alzheimer\'s disease. Focal accumulation of iron may deprive other brain tissues of these essential metals, leading to abnormal neuronal function.

Parkinson Disease: Patients with Parkinson\'s disease have increased total nigrostriatal iron concentrations, and the high concentrations of iron detected in the substantia nigra may exceed the iron-buffering capacity of complexes such as neuromelanin and ferritin and may induce neurotoxicity.

Friedreich\'s Ataxia: Friedreich\'s ataxia (also known as FA or FRDA) is a genetic disorder that causes progressive damage to the nervous system. It can lead to muscle weakness, speech difficulties or heart disease.

Multiple Sclerosis: Elevated iron concentrations occur in specific brain regions in multiple sclerosis, most notably in deep gray matter structures, and increase in many deep gray matter structures as multiple sclerosis progresses.

Huntington\'s Disease: Alterations in brain iron metabolism with increased iron accumulation were identified in the striata of patients with Huntington\'s disease and in particular the basal ganglia.

Restless Legs Syndrome: Restless legs syndrome is characterized by reduced iron function. The reduced iron concentration in the substantia nigra of patients with restless legs syndrome correlates with the severity of the disease.

Mitochondria Iron Metabolism Abnormalities in Neurodegenerative Diseases

In Friedreich\'s ataxia (FA), mutations in mitochondrial FXN lead to impaired Fe-S cluster biogenesis, which further leads to disruption of iron metabolism and an increase in mitochondrial iron content. In Huntington\'s disease (HD), the presence of mutant mHTT leads to increased sensitivity of NMDA receptors, and mHTT interacts with mitochondria, resulting in impaired mitochondrial membrane permeability.