A Study Into the Underlying Biochemical Pathways Involved in Parkinson's Disease, Such as Mitochondrial (Cellular "Powerhouse") Dysfunction
A Study Into the Underlying Biochemical Pathways Involved in Parkinson's Disease, Such as Mitochondrial (Cellular "Powerhouse") Dysfunction
Parkinson's disease (PD) is a progressive neurological disorder that is increasingly common
 with age, with the incidence rising from approximately 4 people per 10,000 in their forties
 to 2 in 100 over the age of eighty.

 Our understanding of the causes of PD has rapidly developed in the past two decades, but this
 has not yet translated into any clinically established neuroprotective treatment that slows
 disease progression. There is a growing consensus that the failure of previous efforts is
 mainly due to the causative diversity of PD i.e. that PD may have many different causes. For
 example, it is known that variants in mitochondrial (cellular power house) genes can cause
 specific forms of PD and this may be relevant to other forms of PD.

 The aim of this study is to attempt to group PD patients based on markers of biochemical
 dysfunction (e.g. into groups of patients that do and those who do not have evidence of
 mitochondrial dysfunction) to aid in the development of new candidate neuro-protective
 compounds.

 The investigators hope by grouping people with Parkinson's into those with and without
 impaired mitochondrial function the investigators will be better able to develop more
 targeted treatments aimed at protecting further loss of brain cells that occurs in
 Parkinson's disease.

 To achieve this the investigators will study people, in two study sites in London, with both
 genetic forms of PD and those with idiopathic PD (i.e. those where there is not a known
 genetic variant causing PD), as well as a healthy control group. All groups will undergo
 standardised clinical assessment to collect information on several aspects of their condition
 (e.g. disease severity, memory problems and sleep problems).

 Participants will be asked to provide blood, urine and optionally cerebrospinal fluid & skin
 samples from which various biochemical assays and genetic analysis will be performed in
 attempt to group participants based on the results of these tests. The study is funded for 3
 years with participants being asked to attend for up to 3 study visits each over this time
 period.
Parkinson's disease (PD) is a progressive neurological disorder that is increasingly
 prevalent with age, with the incidence rising from approximately 4 people per 10,000 in their
 forties to 2 in 100 over the age of eighty. Besides motor symptoms, such as tremor, rigidity,
 bradykinesia, and postural instability, PD patients often experience a variety of non-motor
 symptoms, such as fatigue, depression, sleep disturbance, and dementia.

 Although symptomatic treatments exist to partially compensate for motor dysfunction, no
 neuroprotective treatment has yet been established to slow PD progression, which inevitably
 renders patients incapable of living independently. Compared to age- and sex-matched
 controls, PD patients are about 5 times more likely to require nursing home care and this
 care costs about 5 times more than average nursing home care. This, combined with the
 European demographic shift toward an increasingly larger fraction of aged individuals,
 creates a social and economic challenge to develop new medications to slow the progression of
 PD.

 Our understanding of the aetiopathogenesis of PD has rapidly developed in the past two
 decades, but this has not yet translated into any clinically established neuroprotective
 treatment that slows disease progression. There is a growing consensus that the failure of
 previous efforts is mainly due to the aetiopathogenic diversity of PD and the estrangement of
 existing preclinical models from clinical PD. For example, it is known that mutations in
 mitochondrial genes can cause monogenic PD and biochemical evidence indicates that in a
 proportion of cases, idiopathic PD is associated with detectable mitochondrial dysfunction.

 Therefore, the investigators focus is on monogenic forms of PD that involve mitochondrial
 abnormalities as a primary (e.g., Parkin, PINK1), or secondary (e.g., LRRK2, GBA1)
 phenomenon, in order to extrapolate to idiopathic PD (IPD) patients with and without
 mitochondrial dysfunction (Mito-IPD and Amito-IPD, respectively). Biochemical pathways
 focusing on, but not restricted to mitochondrial function, will be assessed using a variety
 of techniques including biochemical assays on blood, urine, CSF and tissue samples. The
 investigators will explore both the relevance and measurement of specific biochemical
 pathways in Parkinson's and related disorders

 The main overall objective is to stratify PD patients based on dysfunction in biochemical
 pathways related to PD. This will aid in developing new candidate neuroprotection compounds
 to slow the progression of neurodegeneration.
Inclusion Criteria:

 1. Diagnosed with PD, or a related condition (e.g. Parkinson's plus, dystonia, tremor) or
 healthy control participant

 2. Age 18 years or over

 Exclusion Criteria:

 1. Lack of capacity to consent to participate in the project