This leads to problems with movement, tremors, stiffness and impaired balance, and over time difficulty with motor skills such as walking. The most common symptoms result from the loss of neurons in the substantia nigra, near the base of the brain, which produce dopamine— the chemical messenger that enables smooth, purposeful movement. By the time symptoms appear, most people with PD have lost 60 – 80 % or more of these cells.
People with PD also lose nerve endings that produce norepinephrine, the main messenger for the part of the nervous system controlling automatic functions such as pulse and blood pressure; this may explain non-motor symptoms like fatigue and blood-pressure changes. Affected brain cells also accumulate Lewy bodies— deposits of the protein alpha-synuclein— which may build up when the cell’ s protein-disposal system fails, triggering cell death. The average age of onset is the early-to-mid 60s, although a small proportion of people have“ early-onset” PD before age 50.
Current treatments
None of the treatments in use can cure PD, but many reduce symptoms and allow a near-normal lifespan. Supportive therapies— physiotherapy to ease muscle stiffness and joint pain, occupational therapy to maintain independence— help with day-to-day life but work less directly. Medication is the more direct route: levodopa generates dopamine, dopamine agonists act as a dopamine substitute( sometimes combined with levodopa), and monoamine oxidase-B inhibitors prevent dopamine breakdown. Most people with PD eventually use levodopa. Medication is quicker and more accessible than therapy, but carries side effects— some serious— and tends to lose potency as the body builds tolerance and requires higher doses.
Surgery is rarer and not suitable for everyone. Deep brain stimulation implants a pulse generator in the chest wall, delivering small electric currents to affected brain regions to combat symptoms.
It offers a long-term option, but is not equally effective for all patients and carries operative risks. Overall, treatments vary in effectiveness, accessibility, duration and convenience, and any plan should be chosen carefully with a professional.
CRISPR offers the exciting opportunity to edit the harmful-protein-coding genes behind Parkinson’ s, so that the mutations are never expressed in a patient’ s DNA.
CRISPR in Parkinson’ s research
PD and its progression are heavily influenced by genetic factors. Several genes have been identified as key contributors, including SNCA, PARK2, LRRK2, PINK1, GBA, DJ-1, UCHL1 and ATP13A2. SNCA codes for alpha-synuclein, which clumps into Lewy bodies and contributes to the death of dopaminergic neurons. PARK2 normally codes for parkin, a protein that helps cells break down and recycle other proteins; when it is mutated, unwanted proteins build up and drive the same cell death.
Knocking out PARK2 and PINK1 in pigs
CRISPR – Cas9 has already helped reveal the genetics of PD. One study combined CRISPR – Cas9 with somatic cell nuclear transfer— transferring the nucleus of a non-reproductive cell into an egg cell whose nucleus has been removed— to investigate PARK2 and PINK1 in domestic pigs. Both genes encode proteins essential for mitochondrial turnover( the degradation and removal of dysfunctional mitochondria) and mitophagy. The researchers achieved a double knockout of PARK2 and PINK1 with roughly a 38 % success rate, where“ success” meant edited colonies confirmed to be homozygous knockouts for both genes— both alleles deliberately disabled. By eliminating the genes’ expression, researchers could see exactly what happens without them. In this 2015 study, removing PARK2 and PINK1 restored phenotypic abnormalities associated with PD, findings linked to the oxidative stress seen in the disease.
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