Event Review: Degenerative Diseases

From the increase in dementia (1 diagnosis every 3 minutes worldwide) to so-called rare diseases, degenerative conditions affect millions of people globally.

The CETC seminar on 31 March looked at the state of research form 2 angles:

  • the biological understanding of neural degeneration and re-generation and
  • intervention options using either new compounds or re-purposed drugs

Rare Diseases
Health through cell cannibalism?

The human body has great potential to self-heal, as Nicolas Ktitsakis demonstrated in his presentation on autophagy. This cellular recycling mechanism can both produce new nutrients from old stores within the cell and ‘get rid of the rubbish’ that would otherwise build up.
As the largest, laziest cells and most sluggish recyclers in the human body, neurons are particularly vulnerable to the build-up of waste products. Work is under way to determine in which way autophagy can be stimulated to kick-start the regeneration process. This involves both dietary intervention to trigger ‘famine response’ autophagy or by blocking selected protein modulators: the compound rapamycin is known to induce autophagy. Are there others?

The picture is more complicated than first thought.

Dementia comes in many forms and guises, depending on depending on which brain area is affected, as John Skidmore explained in his overview presentation. It can affect mood, memory, personality; it can be vascular or neural in origin; it can develop in old age or – a minority of cases with a clearly hereditary gene defect – hit in earlier adult life.

The complexity of symptoms is mirrored by the complexity of possible causes. 20 genes are associated with the risk of developing late onset dementia, but how these are influenced by lifestyle, immune system, life events is as yet unclear.

The drug discovery alliance (Universities Cambridge, Oxford, UCL) are participating in the effort to identity a ‘disease modifying treatment’ by 2025. Autophagy is a new and promising direction here; could a ‘good cellular recycling regime’ help prevent dementia?

The answer could be out there already

Of the 7000 rare diseases catalogues worldwide, only 400 have treatments options today. As well as causing severe suffering, the cost of repeated misdiagnosis and then, at best, maintenance regimes for patients also has a significant impact on health care costs, as Flora Raffei explained. The business model of the pharmaceutical industry does not really permit heavy investment in new drugs for by default tiny markets, so how can treatments be found?
The charity Findacure encourages researchers to check whether already known and approved compounds could hold the answer to off-prescription treatment of rare diseases – one success story is the imminent approval of such a drug to cure ‘Black Bone Disease’.

The charity hopes to win the support of the NHS for setting up a social bond investment platform to spread the cost of investigations between private investors and the public purse; pharma is contributing pro bono work in the form of access to internal knowledge to the effort to find treatments for rare diseases.