Alzheimer’s disease

The demographic development with an aging population and increasing life expectancy has led to a dramatic increase in the incidence of disease that affect the elderly such as various forms of dementia. Alzheimer’s disease, a fatal illness, is the most common form of dementia accounting for 60 to 80 percent of all diagnosed dementias.

Alzheimer’s disease is estimated to cause 60 – 80 percent of all dementia cases and is thus the most common dementia condition with onset in adulthood (Alzheimer’s Association. 2018 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2018;14(3):367-429). It is estimated that 30 million people worldwide suffer from Alzheimer’s disease today and the number is expected to triple in 30 years.

The disease is characterized by death of neurons in the brain causing a progressive deterioration of memory and cognitive skills, such as intellectual ability, language, orientation, recognition and learning ability. The disease can also lead to personality changes and psychiatric symptoms, for example; apathy, depression, disorientation, paranoia, aggressiveness, and motor symptoms, such as stiffness, reduced mobility and impaired responsiveness.

A patient with far advanced Alzheimer’s disease often suffers from serious cognitive and motor symptoms affecting the ability to care for oneself and handle everyday situations. The disease thus often impairs the quality of life for the patients as well as their families.

The term early Alzheimer’s disease includes Mild Cognitive Impairment (MCI) as a result of Alzheimer’s disease and mild Alzheimer’s disease. Patients with mild Alzheimer’s disease can experience memory problems, confusion, personality changes and depression. Prodromal Alzheimer’s disease is another term for MCI.

The disease progression in Alzheimer’s disease starts several years before the individual exhibits any clinical symptoms. The disease also develops progressively, which means that the symptoms increase as the disease progresses. A disease modifying treatment should preferably be started as early as possible, before the deterioration of the brain has progressed too far.

Alzheimer’s disease is currently diagnosed by clinical investigation, tests of cognitive function, brain imaging and measurement of biomarkers in cerebrospinal fluid. In Alzheimer’s disease significantly elevated levels of amyloid beta can be detected in the brain with positron emission tomography (PET) already at the prodromal stage of the disease. The diagnostic procedure also includes the exclusion of other dementing diseases.

There is currently no cure or treatment that can stop the disease progression. Only symptomatic treatments are currently available on the market.

High unmet medical need

Today approximately 50 million people worldwide are estimated to suffer from some form of dementia disease. In the absence of effective disease modifying treatments that can stop or slow down the disease progression the estimated number of persons with dementia diseases, including Alzheimer’s disease, is expected to reach approximately 152 million before 2050, which highlights the high unmet medical need for innovative drugs in the area (World Alzheimer Report – Alzheimer’s Disease International, 2018).

Halting Alzheimer’s disease progression would lead to great benefits to patients, families and caregivers and cost savings for society considering the huge cost for the care of patients with dementia.

Brain images provided by PET-Centre, Uppsala University Hospital, Sweden, showing a normal brain (left) and an Alzheimer brain (right).

Scientific background

Alzheimer’s disease is caused by accumulation of the amyloid beta peptide in the brain in form of protein aggregates and plaques.

In recent years the knowledge of neurodegenerative disorders has moved from description of symptoms to an understanding of the underlying mechanisms that cause the diseases.

The key molecular events which lead to diseases are today believed to be protein misfolding and spreading of soluble protein aggregates leading to neuronal dysfunction, cell death, brain damage and symptoms of disease (Walsh et al. 1997, Conway et al. 2000). A reduction of these toxic proteins is believed to be of great importance in order to influence the disease progression. BioArctic’s treatment strategy is to reduce or eliminate these toxic proteins in the brain. In this way the progression of the disease may be slowed or halted (Lannfelt et al. 2014).

Oligomers/protofibrils

Amyloid beta aggregation. Toxic oligomers/protofibrils are the target for BioArctic’s Alzheimer’s disease treatment.

In the brains of Alzheimer patients there are plaques mainly containing fibrils of amyloid beta. Each fibril contains millions of single amyloid beta molecules, monomers. The fibrils are so large that they are no longer soluble and will instead form insoluble plaques in the brain tissue. An intermediate stage between monomers and fibrils is oligomers/protofibrils, which are still in solution. Today the general opinion is that it is these soluble, aggregated forms of amyloid beta that are harmful for the brain.

Our approach to Alzheimer’s disease

Amyloid beta immunotherapy has gained a lot of international attention and emerges as one of the most attractive approaches for delaying disease progression in Alzheimer’s disease.

The antibody BAN2401 selectively binds to the soluble, toxic amyloid beta aggregates that are believed to contribute to the neurodegenerative process in early Alzheimer’s disease and eliminates them. BAN2401’s unique profile is highly selective for amyloid beta oligomers/protofibrils in the brain. The aim is to stop or slow down the continuous cognitive impairment in Alzheimer’s disease patients. The project is based on the company’s innovative research in collaboration with Uppsala University, Sweden.

The mouse variant of BAN2401, mAb158, has been demonstrated to considerably reduce the levels of oligomers/protofibrils in the brain (Lord et al. 2009) as well as in the spinal fluid of transgenic mice (Tucker et al. 2015).

Six projects for Alzheimer’s disease

BioArctic’s partner Eisai is responsible for the clinical development of BAN2401 for Alzheimer’s disease. The Phase 3 study (Clarity AD) for early Alzheimers’ disease in ongoing since May 2019. Learn more about the development of the drug candidate BAN2401.

BAN2401 back-up is driven by Eisai and is in preclinical phase.

BioArctic has four additional own Alzheimer projects aimed at slowing down or stopping the disease progression by addressing novel targets: AD1801, AD1502, AD1503 och AD2603. The four projects are in research phase and are all different from each other.

Learn more about BioArctic’s Project Portfolio.

 

We are truly committed to do our outmost to bring innovative and effective disease modifying treatment to patients with early Alzheimer’s disease – a treatment that affects the underlying disease pathology.