THERAPEUTIC FIELD

0 M
patients with Parkinson’s (PD)
and Alzheimer’s (AD) Diseases
0 K
new patients annually in the US

Parkinson’s disease is the fastest growing neurological disorder in the world. Over the past 25 years, the number of people with the condition has jumped from 3 million to over 6 million. By 2040, the number will likely double again. We are failing to stop this onslaught. […] At the same time, our investment in new therapies has lagged behind the disease and many people remain undiagnosed and untreated.

(Dorsey, Sherer, Okun, Bloem. Ending Parkinson’s Disease, 2020)

Barriers in battling brain diseases

Misfolded protein aggregates have been found to be a common hallmark of several neurodegenerative disorders known as proteinopathies. Aggregates not only result in a loss of function of the protein but often overwhelm the clearance system of the cell and become toxic. Parkinson’s and Alzheimer’s diseases are among the most prevalent neurodegenerative proteinopathies.

DISCOVERY

It’s difficult to

source potential new treatments

It’s difficult to

get treatments past the blood brain barrier

DEVELOPMENT

It’s difficult to

predict potential adverse effects

It’s difficult to

know which patients will respond to treatment

There are currently
no disease-modifying treatments for Parkinson’s
and Alzheimer’s diseases

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Parkinson’s disease

affects seven million people worldwide and one million in the US. Parkinson’s disease (PD) is characterized by motor difficulties and non-motor manifestations that can occur years before diagnosis. Motor symptoms are triggered by the degeneration of dopaminergic neurons in the substantia nigra in the mid-brain and include bradykinesia, rigidity and resting tremor. Non-motor symptoms include mood disorders, rem sleep behavior disorder (RBD), anosmia (loss of smell), and constipation. PD pathology is characterized by the misfolding of the synaptic protein α-synuclein that accumulates in cytoplasmic aggregates referred to as Lewy bodies. Recently several studies showed that Lewy bodies are found in the enteric nervous system (ENS) [1] and PD patients endure an imbalance in their gut microbiota composition known as gut dysbiosis [2-3].

Alzheimer’s disease

is the most common form of dementia and affects 44 million people worldwide and more than five million in the US. It is estimated to reach 75 million worldwide by 2030 if no novel approaches to prevent or slow the progression of the disease are found. Alzheimer’s disease (AD) is characterized by several clinical symptoms that include a progressive decline in memory, thinking, speech and learning capacities. AD pathology in characterized by extracellular plaques of insoluble aggregates of amyloid beta (Aß) and intracellular neurofilament tangles of hyperphosphorylated microtubule-associated protein tau. AD patients also show a change in their microbiota compared to healthy individuals [4-5].
Gut microbiota transfer in mouse models of PD and AD highlight a functional link between bacteria composition and neurodegeneration [6-7] indicating that communication between the gut and the brain, namely the gut-brain axis, is linked to neurodegenerative disease.

1- Beach et al., Acta Neuropathol, 2010

2- Scherperjans et al., Movement Disorders, 2015

3- Boertien et al., J Parkinsons Dis, 2019

4- Vogt et al., Sci Rep, 2017

5- Zhuang et al., J Alzheimers Dis, 2018

6- Sampson et al., Cell, 2016

7- Kim et al., Gut, 2020