Giovanna Mallucci

Giovanna Mallucci is a Clinical Neuroscientist and founding Principal Investigator at Altos Labs, Cambridge Institute of Science. She is internationally recognised for her innovative work on neurodegeneration and new therapeutic approaches for Alzheimer's and related diseases, leading to clinical trials.

How has your research into the pathogenic mechanisms of neurodegenerative diseases influenced current therapeutic approaches?

This is very interesting! The real change has come in the shift away from considering neurodegenerative diseases as distinct, individual disorders (Alzheimer's, Parkinson's, ALS, frontotemporal dementias) each with unique pathological causes to be targeted, to the concept of their having shared, common mechanisms of neurodegeneration.  This is something I pioneered from the start of my career: looking at the processes that keep neurons healthy and resistant to damage and degeneration, relevant across all these diseases.  Current approaches increasingly target these pathways, with many laboratories focusing on boosting various 'resilience' mechanisms to prevent and slow neurodegenerative diseases, rather than targeting specific pathologies in single disorders.  These approaches are increasingly seen in clinical trials for these diseases.

Can you tell us about the challenges encountered when developing treatment in therapeutic trials for Alzheimer's-type diseases?

My work is very much at the 'pre-clinical' stage of developing treatments.  This is where work done in mice and in cell experiments leads us scientists to believe in a 'proof of principle', where a drug or treatment looks very promising and 'cures' a mouse model of a human disease, and leads us to want to 'translate' this to possible human treatments.  The difficulties are first that mice clearly are not human and don't naturally get these diseases, so the 'models' are limiting, even if  data showing protection from death of brain cells is compelling and many cellular pathways and mechanisms are very highly shared between mice and humans.

The second—major—challenge is getting drugs that work in mice tested in clinical trials in humans. This is a combination of logistics: organisation, fitness to participate, consent, ethical issues and everything involved in running human clinical trials, and cost - which is invariably very high.  Where new drugs are developed by the pharmacological industry, clinical trials are largely run and highly invested in by these companies. However, where existing drugs, for example, trazodone, are proposed for testing in humans, there is no financial incentive for companies and testing requires governmental support.  So, the challenges are both conceptual: how alike are mice and men? and then logistical: the sheer cost and organisation of human clinical trials.

What do you see as future priorities in neurodegenerative disease research?

Early detection and early intervention.  More resilience-boosting drugs.  More, quicker, smaller, clinical trials: prioritise 'experimental medicines' studies rather than huge clinical trials, where failure to reach a given endpoint represents failure of the trial rather than failure of biology.  We need to persevere.  Harnessing the regenerative properties of other cell types in the brain other than neurons is also exciting and speaks to this broadened perspective on how to treat these disorders.  

Sorbonne University is a leader in biomedical research and interdisciplinary collaboration. How do you see your work on neurodegenerative diseases contributing to or benefiting from the university’s expertise in neuroscience and medical innovation?

Progress is about communication, learning, working together.  It is increasingly clear that real novelty and transformative change comes through conversation and collaboration and going beyond what we can achieve alone.  I am excited to work with and share in the huge creative expertise in Sorbonne University's neuroscience and medical innovation communities, and I hope this honorary doctorate is the beginning of many conversations!