Leptin mimetics for cognitive enhancement and/or neuroprotection
Researchers at the University of Dundee have shown that leptin mimetics have therapeutic potential in neurological disorders such as Alzheimer’s disease
→ Important therapeutic target in Alzheimer's disease
→ Mirrors the cognitive enhancing effects of leptin in episodic-like memory tasks
→ Boosts the synaptic insertion of AMPA receptors
→ Facilitates activity-dependant hippocampal synaptic plasticity
→ Prevents neuronal cell death
Alzheimer’s disease (AD) is a complex, progressive brain disorder, which affects more than 25 million people in the world today and is growing in incidence due to the ageing population. Current approved drugs do not prevent or reverse the disease and there is clear unmet clinical need for truly disease modifying therapies that target the underlying mechanisms.
Clinical evidence indicates that diet and lifestyle are major risk factors for developing the condition and metabolic disruption is common in AD. The metabolic hormone leptin plays an important role both in energy homeostasis and also markedly influences hippocampal synaptic dysfunction. Impaired leptin function has been implicated in AD, thus there is focus on the leptin system as a therapeutic target and source of novel therapeutics.
It is well documented that leptin has cognitive enhancing properties but is not suitable itself as a therapeutic agent due to the size of the protein and widespread central actions. One approach is to produce smaller leptin mimetics that mimic leptin action and are specific to the CNS.
Researchers at the University of Dundee have shown that the leptin fragment 116-130 and other related shorter peptides designed around this region mirrors the cognitive enhancing effects of leptin as it promotes trafficking of the AMPA receptor subunit GluA1 to synapses, and facilitates activity-dependant hippocampal synaptic plasticity. Leptin 116-130 was also found to mirror the cognitive enhancing effects of leptin by enhancing performance in episodic-like memory tasks. Moreover, leptin 116-130 prevented hippocampal synaptic disruption and neuronal cell death in cellular models of amyloid toxicity.
Further work is now being carried out to produce smaller, novel, peptide mimetics which mirror the cognitive enhancing and neuroprotective effects of leptin 116-130 with enhanced stability and bioactivity.
The work has reinforced consensus that the leptin system is an important therapeutic target in AD and also established that leptin 116-130 and other related shorter peptides designed around this region, may be useful in the development of leptin-mimetic agents for therapeutic use.
The worldwide market for Cognitive and Memory Enhancer Drugs is expected to grow at a CAGR of roughly 8.7% over the next five years and will reach 6810 million US$ in 2023.
The University is seeking a commercial partner for this technology and contact is welcomed from organisations interested in developing, licensing or exploiting this opportunity.
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IP Status: Stemming from the priority filing US 62/553,050 dated 31st August 2017, the technology is protected by international patent application PCT/GB2018/052441 filed 30th August 2017 and published as WO 2019/043382 A1 on the 7th March 2019.
- A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin. Malekizadeh Y, Holiday A, Redfearn D, Ainge JA, Doherty G, Harvey J. Cereb Cortex. 2017 Oct 1;27(10):4769-4782. doi: 10.1093/cercor/bhw272.
- Global Cognitive And Memory Enhancer Drugs Market 2018 By Manufacturers, Regions, Type And Application, Forecast To 2023, Market Research Study, Nov 2018.