MANF (mesencephalic-astrocyte-derived neurotrophic factor)

MANF (mesencephalic-astrocyte-derived neurotrophic factor) is believed to have broad potential because it is a naturally-occurring protein produced by the body for the purpose of reducing and preventing apoptosis (cell death) in response to injury or disease, via the unfolded protein response. By manufacturing MANF and administering it to the body, Amarantus is seeking to use a regenerative medicine approach to assist the body with higher quantities of MANF when needed. Amarantus is the front-runner and primary holder of intellectual property (IP) around MANF, and is initially focusing on the development of MANF-based protein therapeutics.

MANF’s lead indication is retinitis pigmentosa, and additional indications including retinal arterial occlusion, Wolfram’s syndrome, Parkinson’s disease and diabetes are currently pursued. Further applications for MANF may include myocardial infarction, hearing loss, otology, and other apoptosis-related disorders  currently under evaluation.

Amarantus entered into a manufacturing agreement with Catalent Pharma Solutions for clinical-grade production of MANF. Catalent will provide all cell line engineering, process development and clinical Good Manufacturing Practices (cGMP) biomanufacturing activities necessary for the rapid development of a high performance cell line expressing MANF protein that will thereafter be advanced into scale up for cGMP production.

Amarantus is initiating Investigational New Drug enabling (IND-enabling) studies to support a first-in-man clinical study with MANF. The company has retained regulatory expertise to identify the fastest path to human proof-of-concept data by evaluating well-respected regulatory pathways available worldwide and is targeting the initiation of first-in-man clinical studies for MANF in 2016.

Retinitis pigmentosa (RP) refers to a group of inherited diseases causing retinal degeneration often leading to blindness. The cell-rich retina lines the inside back wall of the eye and is responsible for capturing images from the visual field. People with RP experience a gradual decline in their vision because photoreceptor cells (rods and cones) die. Symptoms include a progressive degeneration of peripheral and night vision, as well as the degeneration in color perception and central vision. Night blindness is one of the earliest and most frequent symptoms of RP. RP is typically diagnosed in adolescents and young adults. The rate of progression and degree of visual loss varies from person to person. Most people with RP are legally blind by age 40.

Parkinson’s disease (PD) is a neurodegenerative disorder and belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. PD usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of PD patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions. There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.

Current approved therapies treat only the symptoms of Parkinson’s disease. There is an urgent medical need for curative treatments for Parkinson’s disease that fills the fundamental gap in treatment: arresting disease progression. MANF, a neurotrophic factor indicated for the treatment of Parkinson’s disease, offers the promise of safely and effectively protecting dopamine producing neurons from death and rejuvenating dying cells to ultimately stop the progress of Parkinson’s disease and restore normal function to patients.


Diabetes is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced. There are three main types of diabetes.

  • Type 1 results from the body’s failure to produce insulin, and currently requires the person to inject insulin or wear an insulin pump. This form was previously referred to as “insulin-dependent diabetes or “juvenile diabetes”.
  • Type 2 results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes or “adult-onset diabetes”.
  • The third main form, gestational diabetes, occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede development of type 2.


Ischemic Heart Disease (IHD) is a disease characterized by reduced blood supply to the heart muscle, usually due to atherosclerosis of the coronary arteries. Its risk increases with age, smoking, high cholesterol levels, diabetes and hypertension. It is more common in men and those who have a family history of IHD.

Symptoms of stable IHD include angina and decreased exercise tolerance. Unstable IHD presents itself as chest pain or other symptoms at rest, or rapidly worsening angina. Diagnosis of IHD is with an electrocardiogram, blood tests (cardiac markers), cardiac stress testing or a coronary angiogram. Depending on the symptoms and risk, treatment may be with medication, percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as a heart attack is caused by interruption of blood supply to parts of the heart, causing some heart cells to die. This is most commonly due to blockage of a coronary artery associated with an atherosclerotic plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery. The resulting ischemia and associated oxygen shortage, if left untreated for a sufficient period of time, can cause necrosis followed by apoptosis or Programmed Cell Death in the affected parts of the myocardium. Classical symptoms of acute myocardial infarction include sudden chest pain, shortness of breath, nausea, vomiting, palpitations and sweating. Approximately 25% of all myocardial infarctions are silent, without chest pain or other symptoms.

Ischemic Heart Disease is the most common cause of death in most Western countries, and a major cause of hospital admissions. There is limited evidence for population screening, but prevention is used both to prevent IHD and to decrease the risk of complications. Myocardial Infarctions are one of the leading causes of death for both men and women all over the world. Important risk factors are previous cardiovascular disease, older age, tobacco smoking, high blood levels of certain lipids and low levels of high density lipoprotein, diabetes, high blood pressure, obesity, chronic kidney disease, excessive alcohol consumption, and chronic high stress levels.

The common theme of the many forms of IHD, including myocardial infarction, that have been characterized is the pathway of apoptosis-related cell death associated with reperfusion related injuries. MANF has been shown to be robustly upregulated, and to protect heart muscle in reperfusion models of cardiac ischemia.


Retinal artery occlusion affects the eye, or more specifically, the retina. An artery occlusion occurs when the arteries carrying blood to the retina becomes blocked or contains a blood clot. A blockage in the artery of the retina can cause blood or other fluids to build up and affect the retina’s ability to filter light properly. When light is blocked or fluids are present, sudden loss of vision can occur. The severity of vision loss may be dependent upon where the blockage or clot occurred.


Wolfram syndrome is a rare genetic disorder that affects roughly 300 people and causes diabetes mellitus, optic atrophy, deafness and other neurologic problems. It is typically diagnosed in early adolescence and patients die by the age of 30. According to the World Health Organization, the prevalence of diabetes is expected to increase from 171 million patients in 2000, to 366 million patients by 2030. The global market for diabetes products currently stands at $41B and is estimated to grow to $118B by 2018. The United States accounts for approximately 37 percent of the global market, and that share is expected to shrink to 28 percent as emerging markets begin to consume diabetes products. A product such as MANF that could alter the underlying progression of beta cell degeneration could have a significant impact on the market for Wolfram’s and diabetes products.