Delivering antibodies (molecular weight = 150 kDa) to the brain

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Over the last three decades a new therapeutic, the antibody has been introduced. Antibodies are large molecules which are at least 300 times larger than the molecules that are usually used to treat patients. These antibodies are very successful therapies and form the basis of the pharmaceutical industry's recent prosperity. However there are two key problems associated with antibody medicines. One problem is that antibodies have to be given by injection as they are destroyed in the stomach and intestines and cannot cross the intestinal wall to get into the blood; antibodies need to be in the blood to act on their therapeutic target. This makes antibody medicines expensive. However a more important problem is that when antibodies are in the blood, they cannot cross the blood vessels in the brain to get to the brain tissue. This inability to access the brain is due to their large size and good solubility in the blood. Exclusion from the brain makes it hard for antibodies to be used to treat brain diseases such as Alzheimer's disease (AD) and brain tumours and yet these are diseases that are becoming more widespread in our populations, e.g. there are almost half a million AD sufferers in the UK. The current consortium aims to develop antibody medicines that are active in the brain and hence useful for the treatment of conditions such as dementia and brain cancer. In previous collaborations (grant reference numbers - EP/G061483/1 and EP/G028362/1), the applicants had identified a key technological advance that underpins the current application. They found that a particular type of nanoparticle, with a diameter 1/1000th of the thickness of a human hair, is able to cause delicate drugs known as peptides to be absorbed from the intestines; peptides are not normally absorbed when taken by mouth. These tiny particles act by protecting the peptide from degradation in the intestines and stomach and transporting the encapsulated peptide from the intestine to the blood. This former work is pertinent to the current initiative as in the current work, the applicants hypothesise that antibody particles of a similar chemistry should be able to deliver antibodies to the brain via the nose. The applicants have shown that when peptides are dosed in these same particles through the nose the particles are taken up by the brain and the peptides act almost exclusively in the brain. This exciting finding forms the bases of the nasal antibody dosage forms that the group wish to develop. Nanomerics Ltd, a UCL spin out company and member of the current consortium is actually developing an analgesic for the treatment of chronic pain, based on the peptides studied in the earlier funded projects. Chronic pain is a condition suffered by an estimated 20% of European adults and it is poorly served by current drugs. Only a quarter of patients, suffering from the extremely painful chronic neuropathic pain, experience any relief from their symptoms with existing therapies.The group thus has experience in activities aimed at translating scientific findings into real world solutions and the antibody delivery project is aimed at new therapeutics for dementia and cancer patients. The project will be delivered by scientists at UCL, Exeter University, Nanomerics and H. Lundbeck. H. Lundbeck, a global pharmaceutical company with annual revenues of £2 billion, specialises in the treatment of brain diseases. The combination of Nanomerics (which has an exclusive licence to the delivery system's intellectual property), H. Lundbeck (with experience of taking products to market) and academic scientists is ideal for taking a new concept from early stage testing on to a marketed product. The project will involve chemical reactions, nanoscience experiments, microscopical examinations with specialist lasers, cell based tests and animal testing.