Parkinson’s disease

Parkinson’s disease is a progressive and degenerative neurological condition which impairs patients' everyday movement and speech. It occurs as a result of loss of nerve cells in the substantia nigra, the area of the brain responsible for producing dopamine. Dopamine is a chemical that is critical for co-ordinating and determining movement and when dopamine-producing cells are depleted, parts of the brain are unable to function normally, thus leading to movement and speech impairment. Dopamine replacement therapy (L-DOPA, dopamine agonists) works well at first but drug effect is limited by poor absorption and a short duration of effect, as well as by the onset of involuntary movements (dyskinesia), and drug effect also lessens as the disease advances.

Epilepsy

Epilepsy is a chronic neurological disorder characterised by a tendency of patients to have recurrent seizures. A seizure is caused by a sudden burst of excess electrical activity in the brain, causing a temporary disruption in the communication between brain cells. This disruption results in severely abnormal brain function and consequent physical manifestations. It is the most common serious neurological condition in the UK and possibly the world. Epilepsy is more common in children and people over 65, but anyone can develop epilepsy. There can be a known cause for a person’s epilepsy, such as a genetic predisposition, head injury, infections like meningitis, the brain not developing properly, a stroke, or a scar or tumour on the brain. The main treatment for epilepsy is the use of anti-convulsant medications, many of which have negative side effects. However, since there are many sub-types of epilepsy, changes of medication are common and combination/add-on therapies are frequently used.

Alzheimer’s disease

Alzheimer’s disease, the most common form of dementia, is a progressive condition. During the course of the disease, the function of nerves, brain cells and neurotransmitters are increasingly impaired, while plaques and tangles develop in the brain. These plaques and tangles in turn destroy more connections between the brain cells, which aggravates the condition. Consequently, there is a gradual deterioration in elements of memory, attention and information processing. The complex changes that occur in the areas of the brain responsible for these faculties makes Alzheimer’s disease a challenging illness to treat. At this point in time, only the mild, early stages of the disease respond to the available drug treatments (cholinesterase inhibitors, memantine) and nothing currently addresses the more complex components of the illness or stops its progression.

Inflammation/neuro-inflammation

Inflammation is the response by the body to noxious stimuli that is critical to removing the stimuli and starting the healing process. It is a necessary and complicated response involving the immune system and other cells. However inflammation, particularly chronic inflammation, can result in damage to tissues and lead to conditions such as rheumatoid arthrtitis, chronic obstructive pulmonary disease, asthma, fibrosis and many other conditions. Resolution of inflammation is key to reducing longer term tissue damage. Current therapies for inflammation do provide relief for some patients with chronic inflammation but these treatments are often steroids, with the many unwanted side effects associated with this class of drugs, or expensive biologics with inconvenient routes of administration. The prevalence of conditions such as rheumatoid arthritis is growing rapidly with over 4.7m current sufferers in the seven major markets and rising to 5.2m in 2019. Critically, around 30% of patients fail to respond to current therapies. Orally active, small molecule anti-inflammatories with novel modes of action are needed to provide alternative treatment options for patients who respond poorly to exisitng treatments or suffer intolerable side effects. Proximagen is working on a number of small molecule programmes aimed at developing the next generation of anti-inflammatories.

Oncology/neuro-oncology

The incidence of cancer will continue to rise with the ageing population. There are over 3.5m current cancer sufferers in the seven major markets and in many cases the cancers are poorly treated resulting in low survival rates. Every two minutes someone in the UK is diagnosed with cancer and more than one in three people will develop some form of cancer during their lifetime. There are over 200 different types of cancer but for some of the most common significant improvements have been made in diagnosing and treating through coordinated screening campaigns and new, targeted therapies. However, there is a clear medical need for cancer therapies that target the fundamental processes involved in tumour growth and proliferation. The supply of blood to a growing tumour can be reduced through targeting vascular endothelial growth factor (VEGF) and related factors but there is growing evidence that the effects of VEGF inhibition are transitory and that the tumour establishes a secondary source of blood supply mediated through different pathways. Metastases, the spread of cancer to other tissues and organs, is a key feature of cancer and the resulting secondary cancers are thought to be responsible for the majority of deaths. Proximagen is working on new approaches to reducing metastases and inhibiting blood vessel growth which are critical to lowering mortality rates.

Neuropathic pain

Neuropathic pain is a group of disparate disorders of the nervous system which give rise to the sensation of pain, usually in the absence of an external stimulus. It is caused by damage to the nervous system, for example by high glucose levels in the blood (diabetic neuropathic pain), virus induced damage (post-herpetic neuralgia, HIV pain), chemotherapy, cancer, or physical trauma (e.g. in phantom limb pain). Neuropathic pain is a chronic state which may result in a group of symptoms including ‘pins and needles’, extreme sensitivity or complete lack of sensation. Approximately 5% of the population suffers from neuropathic pain, and it is poorly treated by current medications.